BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably limited.AIM T...BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably limited.AIM To assess the therapeutic potential of ginsenoside Rg1 on AA,specifically its protective effects,while elucidating the mechanism at play.METHODS We employed a model of myelosuppression induced by cyclophosphamide(CTX)in C57 mice,followed by administration of ginsenoside Rg1 over 13 d.The invest-igation included examining the bone marrow,thymus and spleen for pathological changes via hematoxylin-eosin staining.Moreover,orbital blood of mice was collected for blood routine examinations.Flow cytometry was employed to identify the impact of ginsenoside Rg1 on cell apoptosis and cycle in the bone marrow of AA mice.Additionally,the study further evaluated cytokine levels with enzyme-linked immunosorbent assay and analyzed the expression of key proteins in the MAPK signaling pathway via western blot.RESULTS Administration of CTX led to significant damage to the bone marrow’s structural integrity and a reduction in hematopoietic cells,establishing a model of AA.Ginsenoside Rg1 successfully reversed hematopoietic dysfunction in AA mice.In comparison to the AA group,ginsenoside Rg1 provided relief by reducing the induction of cell apoptosis and inflammation factors caused by CTX.Furthermore,it helped alleviate the blockade in the cell cycle.Treatment with ginsenoside Rg1 significantly alleviated myelosuppression in mice by inhibiting the MAPK signaling pathway.CONCLUSION This study suggested that ginsenoside Rg1 addresses AA by alleviating myelosuppression,primarily through modulating the MAPK signaling pathway,which paves the way for a novel therapeutic strategy in treating AA,highlighting the potential of ginsenoside Rg1 as a beneficial intervention.展开更多
Objective This study was designed to evaluate the efficacy and safety of aspirin-heparin treatment for un-explained recurrent spontaneous abortion(URSA). Methods Literatures reporting the studies on the aspirin-hepari...Objective This study was designed to evaluate the efficacy and safety of aspirin-heparin treatment for un-explained recurrent spontaneous abortion(URSA). Methods Literatures reporting the studies on the aspirin-heparin treatment of un-explained recurrent miscarriage with randomized controlled trials(RCTs) were collected from the major publication databases. The live birth rate was used as primary indicator, preterm delivery, preeclampsia, intrauterine growth restriction, and adverse reactions(thrombocytopenia) were used as the secondary indicators. The quality of the included studies was evaluated using RCT bias risk assessment tool in the Cochrane Handbook(v5.1.0). Meta-analysis was conducted using RevM an(v5.3) software. Subgroup analyses were conducted with an appropriately combined model according to the type of the treatments if heterogeneity among the selected studies was detected. Results Six publications of RCTs were included in this study. There were a total of 907 pregnant women with diagnosis of URSA, 367 of them were pooled in the study group with aspirin-heparin therapy and 540 women in the control group with placebo, aspirin or progesterone therapy. Meta-analysis showed that the live birth rate in the study group was significantly different from that in the control group [RR = 1.18, 95% CI(1.00-1.39), P=0.04]. Considering the clinical heterogeneity among the six studies, subgroup analysis were performed. Live birth rates in the aspirin-heparin treated groups and placebo groups were compared and no significant difference was found. There were no significant differences found between the two groups in the incidence of preterm delivery [RR=1.22, 95% CI(0.54-2.76), P=0.64], preeclampsia [RR=0.52, 95% CI(0.25-1.07), P=0.08], intrauterine growth restriction [RR=1.19, 95% CI(0.56-2.52), P=0.45] and thrombocytopenia [RR=1.17, 95% CI(0.09-14.42), P=0.90]. Conclusion This meta-analysis did not provide evidence that aspirin-heparin therapy had beneficial effect on un-explained recurrent miscarriage in terms of live birth rate, but it was relatively safe for it did not increase incidence of adverse pregnancy and adverse events. More well-designed and stratified double-blind RCT, individual-based meta-analysis regarding aspirin-heparin therapy are needed in future.展开更多
Objective To gain insight on how exercise affects the outcomes of prostate cancer patients treated with androgen deprivation therapy,specifically cancer-related fatigue(CRF) and quality of life(QoL). Methods Systemati...Objective To gain insight on how exercise affects the outcomes of prostate cancer patients treated with androgen deprivation therapy,specifically cancer-related fatigue(CRF) and quality of life(QoL). Methods Systematic searches for randomized clinical trials(RCTs) evaluating the effects of exercise on CRF and QoL of prostate cancer patients receiving androgen deprivation therapy were carried out to identify the eligible studies from EMBASE,Pub Med and Cochrane library. Related data were extracted from eligible studies and then subjected to Reviewer Manage 5.3 for analysis. Standardized mean differences(SMD) and its 95% confidence interval(CI) were calculated. Results In all,10 RCTs involving 841 prostate cancer patients(448 of whom exercised and 393 did not) were included in this study. With respect to CRF,there was good consistency among different studies,and it was remarkably reduced in the exercise group(SMD=-0.32,95% CI:-0.45 to-0.18,P<0.00001,n=784). In regards to QoL,there was also good consistency among different studies,and it was also improved significantly in the exercise group(SMD=0.21,95% CI:0.08 to 0.34,P=0.002,n=841). Conclusion Exercise both reduced CRF and improved QoL in prostate cancer patients receiving androgen deprivation therapy.展开更多
BACKGROUND Camrelizumab(SHR-1210),an immune checkpoint inhibitor,is clinically used as a therapeutic option for various types of tumors.However,reports of adverse reactions associated with camrelizumab are gradually i...BACKGROUND Camrelizumab(SHR-1210),an immune checkpoint inhibitor,is clinically used as a therapeutic option for various types of tumors.However,reports of adverse reactions associated with camrelizumab are gradually increasing.Anaphylactic shock due to camrelizumab has not been reported previously,until now.We report here,for the first time,a case of anaphylactic shock associated with camrelizumab in a patient with esophageal squamous cell carcinoma.CASE SUMMARY An 84-year-old male esophageal cancer patient received radiotherapy and chemotherapy 11 years ago.He was diagnosed with advanced esophageal squamous cell carcinoma with liver metastasis(Tx N1 M1)and received the first immunotherapy(camrelizumab 200 mg/each time,once every 3 wk)dose in December 2020,with no adverse reactions.Three weeks later,a generalized rash was noted on the chest and upper limbs;palpitations and breathing difficulties with a sense of dying occurred 10 min after the patient had been administered with the second camrelizumab therapy.Electrocardiograph monitoring revealed a 70 beats/min pulse rate,69/24 mm Hg(1 mm Hg=0.133 k Pa)blood pressure,28 breaths/min respiratory rate,and 86%pulse oximetry in room air.The patient was diagnosed with anaphylactic shock and was managed with intravenous fluid,adrenaline,dexamethasone sodium phosphate,calcium glucosate,and noradrenaline.Approximately 2 h after treatment,the patient’s anaphylactic shock symptoms had been completely relieved.CONCLUSION Due to the widespread use of camrelizumab,attention should be paid to anti-programmed cell death 1 antibody therapy-associated hypersensitivity or anaphylactic shock.展开更多
Background:This study investigated the protective effects of L.reuteri ZJ617 on intestinal and liver injury and the underlying mechanisms in modulating inflammatory,autophagy,and apoptosis signaling pathways in a pigl...Background:This study investigated the protective effects of L.reuteri ZJ617 on intestinal and liver injury and the underlying mechanisms in modulating inflammatory,autophagy,and apoptosis signaling pathways in a piglet challenged with lipopolysaccharide(LPS).Methods:Duroc×Landrace×Large White piglets were assigned to 3 groups(n=6/group):control(CON)and LPS groups received oral phosphate-buffered saline for 2 weeks before intraperitoneal injection(i.p.)of physiological saline or LPS(25μg/kg body weight),respectively,while the ZJ617+LPS group was orally inoculated with ZJ617 for 2 weeks before i.p.of LPS.Piglets were sacrificed 4 h after LPS injection to determine intestinal integrity,serum biochemical parameters,inflammatory signaling involved in molecular and liver injury pathways.Results:Compared with controls,LPS stimulation significantly increased intestinal phosphorylated-p38 MAPK,phosphorylated-ERK and JNK protein levels and decreased IκBαprotein expression,while serum LPS,TNF-α,and IL-6 concentrations(P<0.05)increased.ZJ617 pretreatment significantly countered the effects induced by LPS alone,with the exception of p-JNK protein levels.Compared with controls,LPS stimulation significantly increased LC3,Atg5,and Beclin-1 protein expression(P<0.05)but decreased ZO-1,claudin-3,and occludin protein expression(P<0.05)and increased serum DAO and D-xylose levels,effects that were all countered by ZJ617 pretreatment.LPS induced significantly higher hepatic LC3,Atg5,Beclin-1,SOD-2,and Bax protein expression(P<0.05)and lower hepatic total bile acid(TBA)levels(P<0.05)compared with controls.ZJ617 pretreatment significantly decreased hepatic Beclin-1,SOD2,and Bax protein expression(P<0.05)and showed a tendency to decrease hepatic TBA(P=0.0743)induced by LPS treatment.Pretreatment of ZJ617 before LPS injection induced the production of 5 significant metabolites in the intestinal contents:capric acid,isoleucine 1TMS,glycerol-1-phosphate byproduct,linoleic acid,alanine-alanine(P<0.05).Conclusions:These results demonstrated that ZJ617 pretreatment alleviated LPS-induced intestinal tight junction protein destruction,and intestinal and hepatic inflammatory and autophagy signal activation in the piglets.展开更多
Objective: To study the therapeutic effect of Endoscopic ultrasound-guided biliary drainage (EUS-BD) with a nitinol fully covered self-expandable metal stent in patients with malignant obstructive jaundice when endosc...Objective: To study the therapeutic effect of Endoscopic ultrasound-guided biliary drainage (EUS-BD) with a nitinol fully covered self-expandable metal stent in patients with malignant obstructive jaundice when endoscopic retrograde cholangiopancreatography (ERCP) fails. Methods: From January 2016 January 2018, all patients with malignant obstructive jaundice during hospitalization underwent EUS-guided biliary drainage with a nitinol fully covered self-expandable metal stent, and the operation success rate, the clinical success rate, complications, length of hospital stay and survival time were observed. Results: Of 36 patients, 34 cases had successful operation;the operation success rate was 94.44% (34/36). The clinical success rate was 88.89% (32/36). Hemobilia occurred in 1, acute cholangitis in 1, and bile peritonitis in 1;improved after conservative treatment, the complication rate is 8.33% (3/36). Hospital stay and survival time was 21.54 ± 4.73 days and 220.54 ± 54.76 days, respectively. Conclusion: EUS-BD with a nitinol fully covered self-expandable metal stent may be a feasible and effective treatment option in patients with malignant biliary obstruction when ERCP fails.展开更多
Background: In qualitative diagnosis of bile duct stenosis, single diagnostic measure is difficult to make a correct diagnosis, to combine several diagnostic techniques may be helpful to make an accurate diagnosis. T...Background: In qualitative diagnosis of bile duct stenosis, single diagnostic measure is difficult to make a correct diagnosis, to combine several diagnostic techniques may be helpful to make an accurate diagnosis. The aim of this study was to evaluate the value of intraductal ultrasonography (IDUS), endoscopic brush cytology and K-ras, P53 gene mutation in the early diagnosis of malignant biliary stricture. Methods: From February 2012 to February 2013, 84 patients with suspected malignant biliary stricture were performed I DUS firstly, then endoscopic brush cytology and finally K-ras, P53 gene mutation detection, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of all above ways were evaluated and compared. Results: Of 84 patients, 52 cases were ultimately diagnosed malignant biliary stenosis; of which, 9 cases had no recurrence or metastasis to other organs after radical operation during the follow-up period. IDUS combined with brush cytology and K-ras + P53 gene mutation detection had obvious advantage in the sensitivity, accuracy and negative predictive value than any other joint detection and single detection (the advantage was more significant compared with IDUS + brush cytology or any single detection P 〈 0.01). There were obvious statistical significance in the sensitivity and accuracy between IDUS + brush cytology + P53 or IDUS + brush cytology + K-ras and IDUS + brush cytology or IDUS (P 〈 0.05). There was no statistical significance in the sensitivity, specificity, positive predictive value, negative predictive value and accuracy between IDUS + brush cytology + P53 and IDUS + brush cytology + K-ras (P 〉 0.05). Conclusions: IDUS combined with brush cytology and K-ras, P53 gene mutation detection is better than the separate detection and contribute to the early diagnosis of malignant biliary stricture. Its more widespread use is recommended.展开更多
Background:Albuvirtide is a once-weekly injectable human immunodeficiency virus(HIV)-1 fusion inhibitor.We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-riton...Background:Albuvirtide is a once-weekly injectable human immunodeficiency virus(HIV)-1 fusion inhibitor.We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.Methods:We carried out a 48-week,randomized,controlled,open-label non-inferiority trial at 12 sites in China.Adults on the World Health Organization(WHO)-recommended first-line treatment for>6 months with a plasma viral load>1000 copies/mL were enrolled and randomly assigned(1:1)to receive albuvirtide(once weekly)plus ritonavir-boosted lopinavir(ABT group)or the WHO-recommended second-line treatment(NRTI group).The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks.Non-inferiority was prespecified with a margin of 12%.Results:At the time of analysis,week 24 data were available for 83 and 92 patients,and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups,respectively.At 48 weeks,80.4%of patients in the ABT group and 66.0%of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL,meeting the criteria for non-inferiority.For the per-protocol population,the superiority of albuvirtide over NRTI was demonstrated.The frequency of grade 3 to 4 adverse events was similar in the two groups;the most common adverse events were diarrhea,upper respiratory tract infections,and grade 3 to 4 increases in triglyceride concentration.Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.Conclusions:The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug.This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.Trial registration:ClinicalTrials.gov Identifier:NCT02369965;https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No.ChiCTR-TRC-14004276;http://www.chictr.org.cn/enindex.aspx.展开更多
Cardio-cerebrovascular disease(CCVD)is a major comorbidity of coronavirus disease 2019(COVID-19).However,the clinical characteristics and outcomes remain unclear.In this study,102 cases of COVID-19 from January 22,202...Cardio-cerebrovascular disease(CCVD)is a major comorbidity of coronavirus disease 2019(COVID-19).However,the clinical characteristics and outcomes remain unclear.In this study,102 cases of COVID-19 from January 22,2020 to March 26,2020 in Xixi Hospital of Hangzhou were included.Twenty cases had pre-existing CCVD.Results showed that compared with non-CCVD patients,those with CCVD are more likely to develop severe disease(15%versus 1%),and the proportion of pneumonia severity index grade IV was significantly higher(25%versus 3.6%).Computed tomography images demonstrated that the proportion of multiple lobe lesion involvement was significantly higher in the CCVD group than in the non-CCVD group(90%versus 63.4%).Compared with non-CCVD group,the levels of C-reactive protein,fibrinogen,D-dimer,and serum amyloid-A were higher,whereas the total protein and arterial partial Pa02 were lower in the CCVD group.Although no statistical difference was observed in the outcomes between groups,CCVD patients received more intensive comprehensive treatment to improve COVID-19 symptoms compared with non-CCVD patients.Integrated Chinese and Western medicine treatments have certain advantages in controlling the severe conversion rate and mortality of COVID-19.In addition,given that COVID-19 patients are usually related to coagulation disorders and thrombosis risk,the application of Chinese medicine in promoting blood circulation and removing stasis should be strengthened.展开更多
With the number of cases of coronavirus disease-2019(COVID-19)increasing rapidly,the World Health Organization(WHO)has recommended that patients with mild or moderate symptoms could be released from quarantine without...With the number of cases of coronavirus disease-2019(COVID-19)increasing rapidly,the World Health Organization(WHO)has recommended that patients with mild or moderate symptoms could be released from quarantine without nucleic acid retesting,and self-isolate in the community.This may pose a potential virus transmission risk.We aimed to develop a nomogram to predict the duration of viral shedding for individual COVID-19 patients.This retrospective multicentric study enrolled 135 patients as a training cohort and 102 patients as a validation cohort.Significant factors associated with the duration of viral shedding were identified by multivariate Cox modeling in the training cohort and combined to develop a nomogram to predict the probability of viral shedding at 9,13,17,and 21 d after admission.The nomogram was validated in the validation cohort and evaluated by concordance index(C-index),area under the curve(AUC),and calibration curve.A higher absolute lymphocyte count(P=0.001)and lymphocyte-to-monocyte ratio(P=0.013)were correlated with a shorter duration of viral shedding,while a longer activated partial thromboplastin time(P=0.007)prolonged the viral shedding duration.The C-indices of the nomogram were 0.732(95%confidence interval(CI):0.685-0.777)in the training cohort and 0.703(95%CI:0.642-0.764)in the validation cohort.The AUC showed a good discriminative ability(training cohort:0.879,0.762,0.738,and 0.715 for 9,13,17,and 21 d;validation cohort:0.855,0.758,0.728,and 0.706 for 9,13,17,and 21 d),and calibration curves were consistent between outcomes and predictions in both cohorts.A predictive nomogram for viral shedding duration based on three easily accessible factors was developed to help estimate appropriate self-isolation time for patients with mild or moderate symptoms,and to control virus transmission.展开更多
The John Cunningham(JC)polyomavirus was first discovered in a patient with progressive multifocal leukoencephalopathy(PML)in 1971.The diagnosis for PML includes definite(etiological)diagnosis and presumptive(clinical)...The John Cunningham(JC)polyomavirus was first discovered in a patient with progressive multifocal leukoencephalopathy(PML)in 1971.The diagnosis for PML includes definite(etiological)diagnosis and presumptive(clinical)diagnosis.The etiological diagnosis consists of cerebrospinal fluid(CSF)-confirmed PML(evidence of JC polyomavirus in the CSF)and tissue-confirmed PML(evidence of JC polyomavirus in brain tissues).The clinical diagnosis of PML is defined as evidence of typical clinical and magnetic resonance imaging(MRI)findings.[1]JC polyomavirus has a non-enveloped,closed circular double-stranded DNA genome with a full length of 5120 kb.The virus genome is composed of an early coding region,a late coding region,and a non-coding control region(NCCR).The early coding region encodes five proteins:the large tumor(T)antigen,the small T antigen,and three other T antigen-splicing variants(T’135,T’136,and T’165).展开更多
Background and Aims: Chronic hepatitis B virus(HBV)in-fection remains a major public health problem globally.Here,we describe the baseline characteristics and treatment pro-files of HBV-infected patients recruited to ...Background and Aims: Chronic hepatitis B virus(HBV)in-fection remains a major public health problem globally.Here,we describe the baseline characteristics and treatment pro-files of HBV-infected patients recruited to the China Registry of Hepatitis B.Methods: Inclusion criteria were patients with different stages of chronic HBV infection and complete key data.Exclusion criteria were patients with hepatocellular car-cinoma.The baseline clinical,laboratory and treatment pro-files were analyzed.Results: Finally,40,431 patients were included.The median age was 43 years,with 65.2%being men and 51.3%being positive for hepatitis B e antigen(HBeAg).The most common initial diagnosis was chronic hep-atitis B(81.0%),followed by cirrhosis(9.3%),inactive carrier of hepatitis B surface antigen(HBsAg)(6.7%),and immune tolerant phase of hepatitis B infection(3.0%).Among the 21,228 patients who were on treatment,88.0%,10.0%and 2.0%received nucleos(t)ide analogues(NAs),interferon or combination of NAs and interferon,respectively.The propor-tion of patients who received preferred NAs(entecavir or te-nofovir disoproxil fumarate)had increased from 13.5%in 2003 to 79.7%in 2016.Conclusions: We concluded that middle-aged men accounted for most of the patients with chronic hepatitis B in this cross-sectional study.About half of the patients were HBeAg-positive.NAs were the most com-monly used therapy,and use of the preferred NAs had steadily increased in the past decade.展开更多
Background: The domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies ar...Background: The domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (调肝益脾颗粒, TGYP) or Tiaogan-Jianpi-Jiedu Granule (调肝健脾解毒颗粒, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate. Methods: The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus E'IV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment. Discussion: The study was designed to compare the curative effect of CM plus E'IV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "joumey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).展开更多
Objective: To investigate whether analgesic effect of electroacupuncture(EA) is affected by p38 mitogen-activated protein kinase(p38 MAPK) on microglia. Methods: There were two experiments. The experiment 1: 40...Objective: To investigate whether analgesic effect of electroacupuncture(EA) is affected by p38 mitogen-activated protein kinase(p38 MAPK) on microglia. Methods: There were two experiments. The experiment 1: 40 male Sprague-Dawley(SD) rats were randomly divided into the normal, surgery, EA and sham EA groups, and the L5 spinal nerve ligation(SNL) on the right side was used to establish neuropathic pain model. EA was applied to bilateral Zusanli(ST36) and Kunlun(BL60) at 24, 48 and 72 h after SNL for 30 min, once per day. The paw withdrawal thresholds(PWTs) were measured before surgery(as base) and at 24, 25, 49 and 73 h after surgery. Phospho-p38 MAPK(p-p38 MAPK), oxycocin-42(OX-42, marker of microglia), and glial fibrillary acidic protein(GFAP, marker of astrocyte) in bilateral spinal cord dorsal horn(SCDH) were detected by immunofluorescence, respectively. The experiment 2: 40 male SD rats were cannulated for SNL-induced neuropathic pain, and then were randomly divided into the dimethyl sulfoxide(DMSO), EA plus DMSO, 4-(4-fluorophenyl)-2-(4-methylsulfonylpheny)-5-(4-pyridyl)-1H-imidazole(SB203580) and EA plus SB203580 groups. SB203580(30 nmol/L) was administered 5 min prior to EA treatment. The PWTs and OX-42 in bilateral SCDH were measured as mentioned above. Results: SNL-induced neuropathic pain reduced PWTs and increased the expression of p-p38 MAPK and OX-42 in bilateral lumbar SCDH of rats(P〈0.01). Spinal p-p38 MAPK was only co-localized with OX-42 in our study. EA treatment significantly alleviated SNL-mediated mechanical hyperalgesia, and suppressed the expression of p-p38 MAPK and OX-42 in lumbar SCDH(P〈0.05 or P〈0.01). Intrathecal injection of low dose SB203580 had no influence on PWTs(P〉0.05), but significantly inhibited the expression of OX-42 positive cells in bilateral SCDH(P〈0.01 or P〈0.05). EA plus SB203580 synergistically increased PWTs, and reduced the expression of bilateral spinal OX-42(P〈0.01 or P〈0.05). Conclusions: The central mechanism of EA-induced anti-hyperalgesia may be partially associated with the reduced expression of p-p38 MAPK, and subsequently reducing the activation of OX-42 in neuropathic pain. Therefore, EA may be a new complementary and alternative therapy for neuropathic pain.展开更多
Introduction Herbal and dietary supplements(HDS)-induced liver injury has garnered interest in recent years for the increasing trend worldwide[1].Chinese oral herbal paste,a popular herbal formula to enhance immunity ...Introduction Herbal and dietary supplements(HDS)-induced liver injury has garnered interest in recent years for the increasing trend worldwide[1].Chinese oral herbal paste,a popular herbal formula to enhance immunity as HDS in a Chinese medicine clinic,has been less reported to induce liver injury.Here we reported a case of drug reaction with eosinophilia and systemic symptoms(DRESS)syndrome with abrupt transaminitis,which was caused by daily consumption of herbal formulas for 4 weeks.展开更多
Background:Diabetes is a risk factor for acquisition of cryptococcal meningitis(CM).However,the effects of diabetes on outcomes of CM patient have not been fully studied.Methods:In this retrospective study,49 diabetic...Background:Diabetes is a risk factor for acquisition of cryptococcal meningitis(CM).However,the effects of diabetes on outcomes of CM patient have not been fully studied.Methods:In this retrospective study,49 diabetic CM patients and 98 non-diabetic CM patients from January 2008 to December 2018 in the First Affiliated Hospital of Zhejiang University were included by propensity score-matched method(1:2).Demographic characteristics,symptoms,and clinical assay parameters between the two groups were compared.Kaplan-Meier analysis and Cox proportional hazards model were used to assess factors associated with 10-week mortality.Results:The mean age of diabetic patients was 58.2±13.8 years;71.4%(35/49)were more than 50 years old and 46.9%were male.No difference in symptoms was found between diabetic and non-diabetic CM patients.The Charlson comorbidity score was higher in the diabetic group(1.9 vs.0.7,P<0.001).CM patients with diabetes had higher white blood cells count(106/L,111.0(18.0–242.5)vs.50.0(10.0–140.0),P=0.034)in cerebrospinal fluid(CSF),lower CSF India ink positivity(40.8%vs.60.2%,P=0.039),and Cryptococcus culture positivity(42.9%vs.60.2%,P=0.047).The overall 10-week survival rate was 79.7%in diabetic patients vs.83.2%in non-diabetic patients(log-rank P=0.794).Conclusion:Diabetic CM patients have higher CSF glucose and Charlson comorbidity score,but lower CSF India ink and culture positivity than non-diabetic CM patients.No difference in 10-week mortality was found between patients with and without diabetes.Other comorbidities may have a greater effect on prognosis.展开更多
基金Supported by Hangzhou Municipal Bureau of Science and Technology,No.2021WJCY366.
文摘BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably limited.AIM To assess the therapeutic potential of ginsenoside Rg1 on AA,specifically its protective effects,while elucidating the mechanism at play.METHODS We employed a model of myelosuppression induced by cyclophosphamide(CTX)in C57 mice,followed by administration of ginsenoside Rg1 over 13 d.The invest-igation included examining the bone marrow,thymus and spleen for pathological changes via hematoxylin-eosin staining.Moreover,orbital blood of mice was collected for blood routine examinations.Flow cytometry was employed to identify the impact of ginsenoside Rg1 on cell apoptosis and cycle in the bone marrow of AA mice.Additionally,the study further evaluated cytokine levels with enzyme-linked immunosorbent assay and analyzed the expression of key proteins in the MAPK signaling pathway via western blot.RESULTS Administration of CTX led to significant damage to the bone marrow’s structural integrity and a reduction in hematopoietic cells,establishing a model of AA.Ginsenoside Rg1 successfully reversed hematopoietic dysfunction in AA mice.In comparison to the AA group,ginsenoside Rg1 provided relief by reducing the induction of cell apoptosis and inflammation factors caused by CTX.Furthermore,it helped alleviate the blockade in the cell cycle.Treatment with ginsenoside Rg1 significantly alleviated myelosuppression in mice by inhibiting the MAPK signaling pathway.CONCLUSION This study suggested that ginsenoside Rg1 addresses AA by alleviating myelosuppression,primarily through modulating the MAPK signaling pathway,which paves the way for a novel therapeutic strategy in treating AA,highlighting the potential of ginsenoside Rg1 as a beneficial intervention.
文摘Objective This study was designed to evaluate the efficacy and safety of aspirin-heparin treatment for un-explained recurrent spontaneous abortion(URSA). Methods Literatures reporting the studies on the aspirin-heparin treatment of un-explained recurrent miscarriage with randomized controlled trials(RCTs) were collected from the major publication databases. The live birth rate was used as primary indicator, preterm delivery, preeclampsia, intrauterine growth restriction, and adverse reactions(thrombocytopenia) were used as the secondary indicators. The quality of the included studies was evaluated using RCT bias risk assessment tool in the Cochrane Handbook(v5.1.0). Meta-analysis was conducted using RevM an(v5.3) software. Subgroup analyses were conducted with an appropriately combined model according to the type of the treatments if heterogeneity among the selected studies was detected. Results Six publications of RCTs were included in this study. There were a total of 907 pregnant women with diagnosis of URSA, 367 of them were pooled in the study group with aspirin-heparin therapy and 540 women in the control group with placebo, aspirin or progesterone therapy. Meta-analysis showed that the live birth rate in the study group was significantly different from that in the control group [RR = 1.18, 95% CI(1.00-1.39), P=0.04]. Considering the clinical heterogeneity among the six studies, subgroup analysis were performed. Live birth rates in the aspirin-heparin treated groups and placebo groups were compared and no significant difference was found. There were no significant differences found between the two groups in the incidence of preterm delivery [RR=1.22, 95% CI(0.54-2.76), P=0.64], preeclampsia [RR=0.52, 95% CI(0.25-1.07), P=0.08], intrauterine growth restriction [RR=1.19, 95% CI(0.56-2.52), P=0.45] and thrombocytopenia [RR=1.17, 95% CI(0.09-14.42), P=0.90]. Conclusion This meta-analysis did not provide evidence that aspirin-heparin therapy had beneficial effect on un-explained recurrent miscarriage in terms of live birth rate, but it was relatively safe for it did not increase incidence of adverse pregnancy and adverse events. More well-designed and stratified double-blind RCT, individual-based meta-analysis regarding aspirin-heparin therapy are needed in future.
文摘Objective To gain insight on how exercise affects the outcomes of prostate cancer patients treated with androgen deprivation therapy,specifically cancer-related fatigue(CRF) and quality of life(QoL). Methods Systematic searches for randomized clinical trials(RCTs) evaluating the effects of exercise on CRF and QoL of prostate cancer patients receiving androgen deprivation therapy were carried out to identify the eligible studies from EMBASE,Pub Med and Cochrane library. Related data were extracted from eligible studies and then subjected to Reviewer Manage 5.3 for analysis. Standardized mean differences(SMD) and its 95% confidence interval(CI) were calculated. Results In all,10 RCTs involving 841 prostate cancer patients(448 of whom exercised and 393 did not) were included in this study. With respect to CRF,there was good consistency among different studies,and it was remarkably reduced in the exercise group(SMD=-0.32,95% CI:-0.45 to-0.18,P<0.00001,n=784). In regards to QoL,there was also good consistency among different studies,and it was also improved significantly in the exercise group(SMD=0.21,95% CI:0.08 to 0.34,P=0.002,n=841). Conclusion Exercise both reduced CRF and improved QoL in prostate cancer patients receiving androgen deprivation therapy.
基金Supported by the National Natural Science Foundation of China,No.81873317the Natural Science Foundation of Zhejiang,No.LSY19H030002the Science and Technology Projects of Hangzhou City,No.20181228Y22。
文摘BACKGROUND Camrelizumab(SHR-1210),an immune checkpoint inhibitor,is clinically used as a therapeutic option for various types of tumors.However,reports of adverse reactions associated with camrelizumab are gradually increasing.Anaphylactic shock due to camrelizumab has not been reported previously,until now.We report here,for the first time,a case of anaphylactic shock associated with camrelizumab in a patient with esophageal squamous cell carcinoma.CASE SUMMARY An 84-year-old male esophageal cancer patient received radiotherapy and chemotherapy 11 years ago.He was diagnosed with advanced esophageal squamous cell carcinoma with liver metastasis(Tx N1 M1)and received the first immunotherapy(camrelizumab 200 mg/each time,once every 3 wk)dose in December 2020,with no adverse reactions.Three weeks later,a generalized rash was noted on the chest and upper limbs;palpitations and breathing difficulties with a sense of dying occurred 10 min after the patient had been administered with the second camrelizumab therapy.Electrocardiograph monitoring revealed a 70 beats/min pulse rate,69/24 mm Hg(1 mm Hg=0.133 k Pa)blood pressure,28 breaths/min respiratory rate,and 86%pulse oximetry in room air.The patient was diagnosed with anaphylactic shock and was managed with intravenous fluid,adrenaline,dexamethasone sodium phosphate,calcium glucosate,and noradrenaline.Approximately 2 h after treatment,the patient’s anaphylactic shock symptoms had been completely relieved.CONCLUSION Due to the widespread use of camrelizumab,attention should be paid to anti-programmed cell death 1 antibody therapy-associated hypersensitivity or anaphylactic shock.
基金This study was supported by the National Natural Science Foundation of China(31672430)the National Key Research and Development Program of China(2017YFD0500502)the Natural Science Foundation of Zhejiang Province(Z19C170001).
文摘Background:This study investigated the protective effects of L.reuteri ZJ617 on intestinal and liver injury and the underlying mechanisms in modulating inflammatory,autophagy,and apoptosis signaling pathways in a piglet challenged with lipopolysaccharide(LPS).Methods:Duroc×Landrace×Large White piglets were assigned to 3 groups(n=6/group):control(CON)and LPS groups received oral phosphate-buffered saline for 2 weeks before intraperitoneal injection(i.p.)of physiological saline or LPS(25μg/kg body weight),respectively,while the ZJ617+LPS group was orally inoculated with ZJ617 for 2 weeks before i.p.of LPS.Piglets were sacrificed 4 h after LPS injection to determine intestinal integrity,serum biochemical parameters,inflammatory signaling involved in molecular and liver injury pathways.Results:Compared with controls,LPS stimulation significantly increased intestinal phosphorylated-p38 MAPK,phosphorylated-ERK and JNK protein levels and decreased IκBαprotein expression,while serum LPS,TNF-α,and IL-6 concentrations(P<0.05)increased.ZJ617 pretreatment significantly countered the effects induced by LPS alone,with the exception of p-JNK protein levels.Compared with controls,LPS stimulation significantly increased LC3,Atg5,and Beclin-1 protein expression(P<0.05)but decreased ZO-1,claudin-3,and occludin protein expression(P<0.05)and increased serum DAO and D-xylose levels,effects that were all countered by ZJ617 pretreatment.LPS induced significantly higher hepatic LC3,Atg5,Beclin-1,SOD-2,and Bax protein expression(P<0.05)and lower hepatic total bile acid(TBA)levels(P<0.05)compared with controls.ZJ617 pretreatment significantly decreased hepatic Beclin-1,SOD2,and Bax protein expression(P<0.05)and showed a tendency to decrease hepatic TBA(P=0.0743)induced by LPS treatment.Pretreatment of ZJ617 before LPS injection induced the production of 5 significant metabolites in the intestinal contents:capric acid,isoleucine 1TMS,glycerol-1-phosphate byproduct,linoleic acid,alanine-alanine(P<0.05).Conclusions:These results demonstrated that ZJ617 pretreatment alleviated LPS-induced intestinal tight junction protein destruction,and intestinal and hepatic inflammatory and autophagy signal activation in the piglets.
文摘Objective: To study the therapeutic effect of Endoscopic ultrasound-guided biliary drainage (EUS-BD) with a nitinol fully covered self-expandable metal stent in patients with malignant obstructive jaundice when endoscopic retrograde cholangiopancreatography (ERCP) fails. Methods: From January 2016 January 2018, all patients with malignant obstructive jaundice during hospitalization underwent EUS-guided biliary drainage with a nitinol fully covered self-expandable metal stent, and the operation success rate, the clinical success rate, complications, length of hospital stay and survival time were observed. Results: Of 36 patients, 34 cases had successful operation;the operation success rate was 94.44% (34/36). The clinical success rate was 88.89% (32/36). Hemobilia occurred in 1, acute cholangitis in 1, and bile peritonitis in 1;improved after conservative treatment, the complication rate is 8.33% (3/36). Hospital stay and survival time was 21.54 ± 4.73 days and 220.54 ± 54.76 days, respectively. Conclusion: EUS-BD with a nitinol fully covered self-expandable metal stent may be a feasible and effective treatment option in patients with malignant biliary obstruction when ERCP fails.
文摘Background: In qualitative diagnosis of bile duct stenosis, single diagnostic measure is difficult to make a correct diagnosis, to combine several diagnostic techniques may be helpful to make an accurate diagnosis. The aim of this study was to evaluate the value of intraductal ultrasonography (IDUS), endoscopic brush cytology and K-ras, P53 gene mutation in the early diagnosis of malignant biliary stricture. Methods: From February 2012 to February 2013, 84 patients with suspected malignant biliary stricture were performed I DUS firstly, then endoscopic brush cytology and finally K-ras, P53 gene mutation detection, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of all above ways were evaluated and compared. Results: Of 84 patients, 52 cases were ultimately diagnosed malignant biliary stenosis; of which, 9 cases had no recurrence or metastasis to other organs after radical operation during the follow-up period. IDUS combined with brush cytology and K-ras + P53 gene mutation detection had obvious advantage in the sensitivity, accuracy and negative predictive value than any other joint detection and single detection (the advantage was more significant compared with IDUS + brush cytology or any single detection P 〈 0.01). There were obvious statistical significance in the sensitivity and accuracy between IDUS + brush cytology + P53 or IDUS + brush cytology + K-ras and IDUS + brush cytology or IDUS (P 〈 0.05). There was no statistical significance in the sensitivity, specificity, positive predictive value, negative predictive value and accuracy between IDUS + brush cytology + P53 and IDUS + brush cytology + K-ras (P 〉 0.05). Conclusions: IDUS combined with brush cytology and K-ras, P53 gene mutation detection is better than the separate detection and contribute to the early diagnosis of malignant biliary stricture. Its more widespread use is recommended.
基金Frontier Biotechnologies Inc.,Ministry of Science and Technology of China(Nos.2013ZX09101001 and 2017ZX09201007)the Beijing Municipal of Science and Technology Major Project(Nos.D141100000314005,D141100000314002,and D161100000416003)+1 种基金the National Natural Science Foundation of China(Nos.81772165,81974303,and 81571973)Beijing Key Laboratory for HIV/AIDS Research(No.BZ0089)。
文摘Background:Albuvirtide is a once-weekly injectable human immunodeficiency virus(HIV)-1 fusion inhibitor.We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.Methods:We carried out a 48-week,randomized,controlled,open-label non-inferiority trial at 12 sites in China.Adults on the World Health Organization(WHO)-recommended first-line treatment for>6 months with a plasma viral load>1000 copies/mL were enrolled and randomly assigned(1:1)to receive albuvirtide(once weekly)plus ritonavir-boosted lopinavir(ABT group)or the WHO-recommended second-line treatment(NRTI group).The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks.Non-inferiority was prespecified with a margin of 12%.Results:At the time of analysis,week 24 data were available for 83 and 92 patients,and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups,respectively.At 48 weeks,80.4%of patients in the ABT group and 66.0%of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL,meeting the criteria for non-inferiority.For the per-protocol population,the superiority of albuvirtide over NRTI was demonstrated.The frequency of grade 3 to 4 adverse events was similar in the two groups;the most common adverse events were diarrhea,upper respiratory tract infections,and grade 3 to 4 increases in triglyceride concentration.Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.Conclusions:The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug.This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.Trial registration:ClinicalTrials.gov Identifier:NCT02369965;https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No.ChiCTR-TRC-14004276;http://www.chictr.org.cn/enindex.aspx.
基金This work was supported by the National Natural Science Foundation of China(No.81930111)Zhejiang Province High-level Talents Project(No.2019R51002).
文摘Cardio-cerebrovascular disease(CCVD)is a major comorbidity of coronavirus disease 2019(COVID-19).However,the clinical characteristics and outcomes remain unclear.In this study,102 cases of COVID-19 from January 22,2020 to March 26,2020 in Xixi Hospital of Hangzhou were included.Twenty cases had pre-existing CCVD.Results showed that compared with non-CCVD patients,those with CCVD are more likely to develop severe disease(15%versus 1%),and the proportion of pneumonia severity index grade IV was significantly higher(25%versus 3.6%).Computed tomography images demonstrated that the proportion of multiple lobe lesion involvement was significantly higher in the CCVD group than in the non-CCVD group(90%versus 63.4%).Compared with non-CCVD group,the levels of C-reactive protein,fibrinogen,D-dimer,and serum amyloid-A were higher,whereas the total protein and arterial partial Pa02 were lower in the CCVD group.Although no statistical difference was observed in the outcomes between groups,CCVD patients received more intensive comprehensive treatment to improve COVID-19 symptoms compared with non-CCVD patients.Integrated Chinese and Western medicine treatments have certain advantages in controlling the severe conversion rate and mortality of COVID-19.In addition,given that COVID-19 patients are usually related to coagulation disorders and thrombosis risk,the application of Chinese medicine in promoting blood circulation and removing stasis should be strengthened.
基金supported by the Medical and Health Science and Technology Project of Zhejiang Province,China(No.2018KY116)。
文摘With the number of cases of coronavirus disease-2019(COVID-19)increasing rapidly,the World Health Organization(WHO)has recommended that patients with mild or moderate symptoms could be released from quarantine without nucleic acid retesting,and self-isolate in the community.This may pose a potential virus transmission risk.We aimed to develop a nomogram to predict the duration of viral shedding for individual COVID-19 patients.This retrospective multicentric study enrolled 135 patients as a training cohort and 102 patients as a validation cohort.Significant factors associated with the duration of viral shedding were identified by multivariate Cox modeling in the training cohort and combined to develop a nomogram to predict the probability of viral shedding at 9,13,17,and 21 d after admission.The nomogram was validated in the validation cohort and evaluated by concordance index(C-index),area under the curve(AUC),and calibration curve.A higher absolute lymphocyte count(P=0.001)and lymphocyte-to-monocyte ratio(P=0.013)were correlated with a shorter duration of viral shedding,while a longer activated partial thromboplastin time(P=0.007)prolonged the viral shedding duration.The C-indices of the nomogram were 0.732(95%confidence interval(CI):0.685-0.777)in the training cohort and 0.703(95%CI:0.642-0.764)in the validation cohort.The AUC showed a good discriminative ability(training cohort:0.879,0.762,0.738,and 0.715 for 9,13,17,and 21 d;validation cohort:0.855,0.758,0.728,and 0.706 for 9,13,17,and 21 d),and calibration curves were consistent between outcomes and predictions in both cohorts.A predictive nomogram for viral shedding duration based on three easily accessible factors was developed to help estimate appropriate self-isolation time for patients with mild or moderate symptoms,and to control virus transmission.
基金This work was supported by a grant from the National Major Science and Technology Projects for Important Infectious Diseases in China(No.2017ZX10202102-002-002)。
文摘The John Cunningham(JC)polyomavirus was first discovered in a patient with progressive multifocal leukoencephalopathy(PML)in 1971.The diagnosis for PML includes definite(etiological)diagnosis and presumptive(clinical)diagnosis.The etiological diagnosis consists of cerebrospinal fluid(CSF)-confirmed PML(evidence of JC polyomavirus in the CSF)and tissue-confirmed PML(evidence of JC polyomavirus in brain tissues).The clinical diagnosis of PML is defined as evidence of typical clinical and magnetic resonance imaging(MRI)findings.[1]JC polyomavirus has a non-enveloped,closed circular double-stranded DNA genome with a full length of 5120 kb.The virus genome is composed of an early coding region,a late coding region,and a non-coding control region(NCCR).The early coding region encodes five proteins:the large tumor(T)antigen,the small T antigen,and three other T antigen-splicing variants(T’135,T’136,and T’165).
文摘Background and Aims: Chronic hepatitis B virus(HBV)in-fection remains a major public health problem globally.Here,we describe the baseline characteristics and treatment pro-files of HBV-infected patients recruited to the China Registry of Hepatitis B.Methods: Inclusion criteria were patients with different stages of chronic HBV infection and complete key data.Exclusion criteria were patients with hepatocellular car-cinoma.The baseline clinical,laboratory and treatment pro-files were analyzed.Results: Finally,40,431 patients were included.The median age was 43 years,with 65.2%being men and 51.3%being positive for hepatitis B e antigen(HBeAg).The most common initial diagnosis was chronic hep-atitis B(81.0%),followed by cirrhosis(9.3%),inactive carrier of hepatitis B surface antigen(HBsAg)(6.7%),and immune tolerant phase of hepatitis B infection(3.0%).Among the 21,228 patients who were on treatment,88.0%,10.0%and 2.0%received nucleos(t)ide analogues(NAs),interferon or combination of NAs and interferon,respectively.The propor-tion of patients who received preferred NAs(entecavir or te-nofovir disoproxil fumarate)had increased from 13.5%in 2003 to 79.7%in 2016.Conclusions: We concluded that middle-aged men accounted for most of the patients with chronic hepatitis B in this cross-sectional study.About half of the patients were HBeAg-positive.NAs were the most com-monly used therapy,and use of the preferred NAs had steadily increased in the past decade.
基金Supported by China National Science and Technology Major Projects 12th 5-year Plan(No.2012ZX10005004)
文摘Background: The domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (调肝益脾颗粒, TGYP) or Tiaogan-Jianpi-Jiedu Granule (调肝健脾解毒颗粒, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate. Methods: The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus E'IV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment. Discussion: The study was designed to compare the curative effect of CM plus E'IV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "joumey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).
基金Supported by National Natural Science Foundation of China(No.81102643)Zhejiang Provincial Natural Science Foundation(No.Y2091151)+1 种基金State Administration of Traditional Chinese Medicine(Acupuncture)of Key Subjects Construction Funding(No.[2009]30)Research Fund of Zhejiang Provincial FirstForemost Key Subject-Acupuncture and Moxibustion(No.[2008]255)
文摘Objective: To investigate whether analgesic effect of electroacupuncture(EA) is affected by p38 mitogen-activated protein kinase(p38 MAPK) on microglia. Methods: There were two experiments. The experiment 1: 40 male Sprague-Dawley(SD) rats were randomly divided into the normal, surgery, EA and sham EA groups, and the L5 spinal nerve ligation(SNL) on the right side was used to establish neuropathic pain model. EA was applied to bilateral Zusanli(ST36) and Kunlun(BL60) at 24, 48 and 72 h after SNL for 30 min, once per day. The paw withdrawal thresholds(PWTs) were measured before surgery(as base) and at 24, 25, 49 and 73 h after surgery. Phospho-p38 MAPK(p-p38 MAPK), oxycocin-42(OX-42, marker of microglia), and glial fibrillary acidic protein(GFAP, marker of astrocyte) in bilateral spinal cord dorsal horn(SCDH) were detected by immunofluorescence, respectively. The experiment 2: 40 male SD rats were cannulated for SNL-induced neuropathic pain, and then were randomly divided into the dimethyl sulfoxide(DMSO), EA plus DMSO, 4-(4-fluorophenyl)-2-(4-methylsulfonylpheny)-5-(4-pyridyl)-1H-imidazole(SB203580) and EA plus SB203580 groups. SB203580(30 nmol/L) was administered 5 min prior to EA treatment. The PWTs and OX-42 in bilateral SCDH were measured as mentioned above. Results: SNL-induced neuropathic pain reduced PWTs and increased the expression of p-p38 MAPK and OX-42 in bilateral lumbar SCDH of rats(P〈0.01). Spinal p-p38 MAPK was only co-localized with OX-42 in our study. EA treatment significantly alleviated SNL-mediated mechanical hyperalgesia, and suppressed the expression of p-p38 MAPK and OX-42 in lumbar SCDH(P〈0.05 or P〈0.01). Intrathecal injection of low dose SB203580 had no influence on PWTs(P〉0.05), but significantly inhibited the expression of OX-42 positive cells in bilateral SCDH(P〈0.01 or P〈0.05). EA plus SB203580 synergistically increased PWTs, and reduced the expression of bilateral spinal OX-42(P〈0.01 or P〈0.05). Conclusions: The central mechanism of EA-induced anti-hyperalgesia may be partially associated with the reduced expression of p-p38 MAPK, and subsequently reducing the activation of OX-42 in neuropathic pain. Therefore, EA may be a new complementary and alternative therapy for neuropathic pain.
基金supported by Medical and Health Research Project of Zhejiang Province(No.2022KY277).
文摘Introduction Herbal and dietary supplements(HDS)-induced liver injury has garnered interest in recent years for the increasing trend worldwide[1].Chinese oral herbal paste,a popular herbal formula to enhance immunity as HDS in a Chinese medicine clinic,has been less reported to induce liver injury.Here we reported a case of drug reaction with eosinophilia and systemic symptoms(DRESS)syndrome with abrupt transaminitis,which was caused by daily consumption of herbal formulas for 4 weeks.
基金This work was supported by the National Science and Technology Major Project of China during the 13th Five-year plan period(2018ZX10302104)Independent Research Foundation of the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,the First Affiliated Hospital,School of Medicine,Zhejiang University(2020ZZ19).
文摘Background:Diabetes is a risk factor for acquisition of cryptococcal meningitis(CM).However,the effects of diabetes on outcomes of CM patient have not been fully studied.Methods:In this retrospective study,49 diabetic CM patients and 98 non-diabetic CM patients from January 2008 to December 2018 in the First Affiliated Hospital of Zhejiang University were included by propensity score-matched method(1:2).Demographic characteristics,symptoms,and clinical assay parameters between the two groups were compared.Kaplan-Meier analysis and Cox proportional hazards model were used to assess factors associated with 10-week mortality.Results:The mean age of diabetic patients was 58.2±13.8 years;71.4%(35/49)were more than 50 years old and 46.9%were male.No difference in symptoms was found between diabetic and non-diabetic CM patients.The Charlson comorbidity score was higher in the diabetic group(1.9 vs.0.7,P<0.001).CM patients with diabetes had higher white blood cells count(106/L,111.0(18.0–242.5)vs.50.0(10.0–140.0),P=0.034)in cerebrospinal fluid(CSF),lower CSF India ink positivity(40.8%vs.60.2%,P=0.039),and Cryptococcus culture positivity(42.9%vs.60.2%,P=0.047).The overall 10-week survival rate was 79.7%in diabetic patients vs.83.2%in non-diabetic patients(log-rank P=0.794).Conclusion:Diabetic CM patients have higher CSF glucose and Charlson comorbidity score,but lower CSF India ink and culture positivity than non-diabetic CM patients.No difference in 10-week mortality was found between patients with and without diabetes.Other comorbidities may have a greater effect on prognosis.