Liver histopathological lesions is severe in patients with normal alanine transaminase and low to moderate hepatitis B virus DNA replication

BACKGROUND Chronic hepatitis B virus(HBV)infection remains a major global public health problem.Chronic hepatitis B(CHB)patients can be divided into treatment indication and non-treatment indication individuals according to alanine transaminase(ALT),HBV DNA,serum hepatitis B e antigen status,disease status[liver cirrhosis,hepatocellular carcinoma(HCC),or liver failure],liver necroinflammation or fibrosis,patients’age,and family history of HCC or cirrhosis.For example,normal ALT patients in‘immune-tolerant’phase with HBV DNA higher than 10^(7)or 2×10^(7)IU/mL,and those in‘inactive-carrier’phase with HBV DNA lower than 2×10^(3)IU/mL do not require antiviral therapy.However,is it reasonable to set the defined values of HBV DNA as the fundamental basis to estimate the disease state and to determine whether to start treatment?In fact,we should pay more attention to those who do not match the treatment indications(grayzone patients both in the indeterminate phase and in the‘inactive-carrier’phase).AIM To analyze the correlation of HBV DNA level and liver histopathological severity,and to explore the significance of HBV DNA for CHB with normal ALT.METHODS From January 2017 to December 2021,a retrospective cross-sectional set of 1299 patients with chronic HBV infection(HBV DNA>30 IU/mL)who underwent liver biopsy from four hospitals,including 634 with ALT less than 40 U/L.None of the patients had received anti-HBV treatment.The degrees of liver necroinflammatory activity and liver fibrosis were evaluated according to the Metavir system.On the basis of the HBV DNA level,patients were divided into two groups:Low/moderate replication group,HBV DNA≤10^(7)IU/mL[7.00 Log IU/mL,the European Association for the Study of the Liver(EASL)guidelines]or≤2×10^(7)IU/mL[7.30 Log IU/mL,the Chinese Medical Association(CMA)guidelines];high replication group,HBV DNA>10^(7)IU/mL or>2×10^(7)IU/mL.Relevant factors(demographic characteristics,laboratory parameters and noninvasive models)for liver histopathological severity were analyzed by univariate analysis,logistics analysis and propensity score-matched analysis.RESULTS At entry,there were 21.45%,24.29%,and 30.28%of the patients had liver histopathological severities with≥A2,≥F2,and≥A2 or/and≥F2,respectively.HBV DNA level(negative correlation)and noninvasive model liver fibrosis 5 value(positive correlation)were independent risk factors for liver histopathological severities(liver necroinflammation,liver fibrosis,and treatment indication).The AUROCs of the prediction probabilities(PRE_)of the models mentioned above(<A2 vs≥A2,<F2 vs≥F2,<A2 and<F2 vs≥A2 or/and≥F2)were 0.814(95%CI:0.770-0.859),0.824(95%CI:0.785-0.863),and 0.799(95%CI:0.760-0.838),respectively.HBV DNA level(negative correlation)was still an independent risk factor when diagnostic models were excluded,the P values(<A2 vs≥A2,<F2 vs≥F2,<A2 and<F2 vs≥A2 or/and≥F2)were 0.011,0.000,and 0.000,respectively.For the propensity score-matched pairs,whether based on EASL guidelines or CMA guidelines,the group with significant liver histology damage(≥A2 or/and≥F2)showed much lower HBV DNA level than the group with non-significant liver histology damage(<A2 and<F2).Patients in the moderate replication group(with indeterminate phase)had the most serious liver disease pathologically and hematologically,followed by patients in the low replication group(with‘inactive-carrier’phase)and then the high replication group(with‘immune-tolerant’phase).CONCLUSION HBV DNA level is a negative risk factor for liver disease progression.The phase definition of CHB may be revised by whether the level of HBV DNA exceeds the detection low limit value.Patients who are in the indeterminate phase or‘inactive carriers’should receive antiviral therapy.

CLINICAL THERAPEUTIC EFFECT OF DRUG-SEPARATED MOXIBUSTION ON CHRONIC DIARRHEA AND ITS IMMUNOLOGIC MECHANISMS

In the present paper it was reported that 24 cases of ulcerative colitis and 23 cases of chronic colitis were treated by drug-separated moxibustion and the total effective rates were 95.83% and 95.65% respectively, which were markedly superior to that of western medicine group. Observation in 15 cases of ulcerative colitis showed that drug-separated moxibustion could inhibit humoral immunity and elevate cellular immune function. The therapy possibly regulated the abnormal ratio of T-lymphocyte subgroups and corrected the abnormal state of autoimmunity of patients, so that pathological changes of intestinal mucosa were corrected effectively.

311 CASES OF CHRONIC OSTEOMYELITIS TREATED BY SOAKING WITH GANLINGSAN LIQUID

From 1992 to 1995, 311 cases of chronic osteomyelitis (including 145 cases of hematogenic osteomyelitis, 147 cases of traumatic osteomyelitis, 8 cases of secondary osteomyelitis after local infection, 4 cases due to other causes, and 7 cases with cause unknown) were treated by soaking with Ganlingsan liquid. The average treatment course was 69.5 days. The results showed that 260 cases were cured, 26 cases markedly effective, 20 cases improved, and 5 cases ineffective. The evaluation of the function revealed that 150 cases were excellent, 129 cases good, 10 cases improved, and 22 cases poor. 111 patients recovered from abnormal erythrocyte sedimentation rate. External fixation was applied at the same time for the patients accompanied by nonunion of fracture, and the therapeutic effect was also satisfactory.

Clinical study on Chuanxiong Hualiu Mixture in the treatment of blood stasis and phlegm stagnation type of ovarian cyst

Objective:To observe the clinical efficacy of Chuanxiong Hualiu Mixture in the treatment of blood stasis and phlegm stagnation type of ovarian cyst and the effects on physical and chemical indicators.Methods: A total of 80 patients with blood stasis and phlegm stagnation type of ovarian cyst were randomly divided into two groups, research group (n=40) took Chuanxiong Hualiu Mixture, control group (n=40) took Guizhi Fuling Capsule, 3 months was a course of treatment, and the curative effect was compared between two groups.Results:(1) The overall response rate of Chuanxiong Hualiu mixture group after 3 months of treatment was 82.5%, that of Guizhi Fuling Capsule group was 62.5%, the overall response rate of Chuanxiong Hualiu mixture group was higher than that of control group, and the difference was statistically significant;(2) before and after treatment, sex hormone and hemorheology index E2 of both groups decreased significantly, whole blood viscosity, whole blood reduced viscosity and plasma viscosity decreased significantly, the results were statistically significant, but there was no difference between two groups;(3) rank sum test of TCM symptom efficacy between two groups before and after treatment showed that the overall response rate of Chuanxiong Hualiu mixture group was 95%, the overall response rate of Guizhi Fuling Capsule group was 85%, the overall response rate of research group was better than that of control group, and the difference was statistically significant.Conclusion:Chuanxiong Hualiu mixture has good curative effect for the treatment of ovarian cyst, it can effectively improve the patients' blood stasis and phlegm stagnation constitution, and its mechanism of action is associated with lowering estrogen levels and improving hemorrheology.

Adhesive hydrogel interface for enhanced epidermal signal

This paper presents a discussion on the method,mechanism,and application of adhesive hydrogel in enhancing epidermal signal,focusing on the interface between hydrogel and skin.Due to its excellent conductivity and high adaptability to the skin,the hydrogel is exceptionally suitable for detecting human-machine interfaces,particularly epidermal electromyographic signals.However,the detection of the high epidermal signal is hindered by the gap and low adhesion between hydrogel and skin.This paper addresses these challenges by introducing approaches to reduce the interface gap and increase interface adhesion,thereby enabling the development of hydrogel-based epidermal signal detection arrays with enhanced resolution and detection performance.

Primary Amebic Meningoencephalitis Caused by Naegleria fowleri in China: A Case Report

Naegleria fowleri is a thermophilic,free-living ameba that is commonly known as the“brain-eating ameba.”This parasite invades the central nervous system and causes an acute fulminant infection,which results in a fatal form of primary amebic meningoencephalitis(PAM).Here,we report a case of PAM by an unexpected transmission route.Regrettably,the patient deteriorated swiftly and passed away subsequent to diagnosis,despite our exhaustive efforts.Here,we compiled a summary of 11 cases of PAM survivors who have all been treated with amphotericin,rifampicin and triazoles.Beside this regimen,miltefosine was also used successfully to treat PAM in an adolescent.More precise understanding of the survival rate and contributing factors can be established with further validation on ad-ditional cases.

Clovibactin:一种对病原体展现致死效应且低耐药性的革命性抗生素

The decades spanning from the 1940s to the 1960s are renowned as the heyday of antibiotic discovery.It was during this era that game-changing antibiotics such as streptomycin,vancomycin,and tetracycline were unearthed,fundamentally reshaping the landscape of modern medicine.However,antibiotic discovery faces alarming challenges and traditional screening has not yielded new drugs in many decades.The crisis of antimicrobial resistance(AMR)emerges as a consequence of the unintended disruption of the antibiotic discovery pipeline and the subsequent uncontrolled proliferation of resistant pathogens[1].According to the World Health Organization(WHO),in 2019,approximately1.2 million people worldwide died of bacterial infections exacerbated by AMR,surpassing the number of deaths caused by HIV/AIDS.If this trend continues,by 2050,AMR could potentially result in over 10 million deaths,surpassing the mortality rate attributed to cancer.Thus,we are in dire need of new antibiotics to counter the rising resistance of bacteria to most currently employed clinical antibiotics.

Discovering deaminases using AlphaFold2:a strategy to search for tool proteins for gene editing

A recent study by Huang et al.published in Cell reported the application of AlphaFold2 to forecast the structures of deaminase proteins and cluster them based on structural similarity,creating a truncated Sdd that can be used as a cytosine base editor(CBE)to be integrated into a single adeno-associated virus(AAV)1 This ground-breaking study aided by the artificial intelligence system would largely broaden the utility of tool proteins for gene editing.

3D-printed porous functional composite scaffolds with polydopamine decoration for bone regeneration

Large size bone defects affect human health and remain a worldwide health problem that needs to be solved immediately.3D printing technology has attracted substantial attention for preparing penetrable multifunctional scaffolds to promote bone reconditioning and regeneration.Inspired by the spongy structure of natural bone,novel porous degradable scaffolds have been printed using polymerization of lactide and caprolactone(PLCL)and bioactive glass 45S5(BG),and polydopamine(PDA)was used to decorate the PLCL/BG scaffolds.The physicochemical properties of the PLCL/BG and PLCL/BG/PDA scaffolds were measured,and their osteogenic and angiogenic effects were characterized through a series of experiments both in vitro and in vivo.The results show that the PLCL/BG2/PDA scaffold possessed a good compression modulus and brilliant hydrophilicity.The proliferation,adhesion and osteogenesis of hBMSCs were improved in the PDA coating groups,which exhibited the best performance.The results of the SD rat cranium defect model indicate that PLCL/BG2/PDA obviously promoted osteointegration,which was further confirmed through immunohistochemical staining.Therefore,PDA decoration and the sustained release of bioactive ions(Ca,Si,P)from BG in the 3D-printed PLCL/BG2/PDA scaffold could improve surface bioactivity and promote better osteogenesis and angiogenesis,which may provide a valuable basis for customized implants in extensive bone defect repair applications.

Targeting TRMT5 suppresses hepatocellular carcinoma progression via inhibiting the HIF-1αpathways

Accumulating evidence has confirmed the links between transfer RNA(tRNA)modifications and tumor progression.The present study is the first to explore the role of tRNA methyltransferase 5(TRMT5),which catalyzes the m1G37 modification of mitochondrial tRNAs in hepatocellular carcinoma(HCC)progression.Here,based on bioinformatics and clinical analyses,we identified that TRMT5 expression was upregulated in HCC,which correlated with poor prognosis.Silencing TRMT5 attenuated HCC proliferation and metastasis both in vivo and in vitro,which may be partially explained by declined extracellular acidification rate(ECAR)and oxygen consumption rate(OCR).Mechanistically,we discovered that knockdown of TRMT5 inactivated the hypoxia-inducible factor-1(HIF-1)signaling pathway by preventing HIF-1αstability through the enhancement of cellular oxygen content.Moreover,our data indicated that inhibition of TRMT5 sensitized HCC to doxorubicin by adjusting HIF-1α.In conclusion,our study revealed that targeting TRMT5 could inhibit HCC progression and increase the susceptibility of tumor cells to chemotherapy drugs.Thus,TRMT5 might be a carcinogenesis candidate gene that could serve as a potential target for HCC therapy.

基于P2X7R-NLRP3炎性小体通路探讨针灸减轻UC大鼠结肠黏膜炎症的作用机制

目的:从P2X7R-NLRP3炎性小体通路角度探讨针灸干预溃疡性结肠炎(UC)的作用机制。方法:将Sprague-Dawley大鼠随机分为正常组、模型组、隔药灸组和电针组。造模方法为4%右旋糖酐硫酸钠连续饮用7d。隔药灸组和电针组分别接受连续7 d隔药灸或电针双侧天枢穴干预。苏木素-伊红(HE)染色法观察结肠组织病理学变化;免疫荧光法检测结肠组织相关分子的蛋白表达;酶联免疫吸附法检测血清和结肠组织相关分子的浓度或含量。采用野生型(WT)和P2X7R基因敲除(KO)小鼠构建UC模型,HE染色观察结肠组织病理学变化;免疫组化法检测结肠组织NLRP3蛋白表达。结果:与正常组比较,模型组结肠组织病理学评分,结肠组织P2X7R、NLRP3、ASC、Caspase-1、IL-1β及IL-18蛋白表达,血清IL-1β及IL-18的蛋白水平均显著升高(P<0.05)。与模型组比较,隔药灸组及电针组结肠组织病理学评分,结肠组织P2X7R、NLRP3、ASC、Caspase-1、IL-1β及IL-18蛋白表达,以及血清IL-18蛋白水平均显著降低(P<0.05)。经UC造模后,P2X7R KO小鼠结肠黏膜上皮损伤及炎性细胞浸润程度较WT小鼠减轻,结肠NLRP3蛋白表达也较WT小鼠降低(P<0.05)。结论:隔药灸、电针天枢穴可能通过抑制UC大鼠结肠组织P2X7R、NLRP3、ASC及Caspase-1的蛋白活性,降低P2X7R-NLRP3炎性小体通路中下游分子IL-1β及IL-18的表达达到缓解UC炎症的目的。

Clinical study on acupuncture plus auricular point sticking for tension-type headache

Objective:To observe the clinical efficacy of acupuncture plus auricular point sticking for tension-type headache(TTH).Methods:A total of 90 TTH patients were divided into an acupuncture group,an auricular point sticking group and an observation group by random number table method,with 30 cases in each group.Patients in the observation group received acupuncture plus auricular point sticking for treatment,while those in the acupuncture group only received acupuncture and those in the auricular point sticking group only received auricular point sticking for treatment.The headache attack frequency and the scores of visual analog scale(VAS),self-rating anxiety scale(SAS)and self-rating depression scale(SDS)were observed before treatment,after treatment and 3 months after treatment.The clinical efficacy was evaluated at the follow-up of 3 months after treatment.Results:At follow-up,there were significant differences in clinical efficacy among the three groups(P<0.01 or P<0.05),and the clinical efficacy ranking from high to low was the observation group,the acupuncture group and the auricular point sticking group.After treatment and at follow-up,the VAS score,headache attack frequency,SAS and SDS scores in the three groups were significantly lower than those before treatment(all P<0.01).The above four results in the observation group were lower than those in the acupuncture group and the auricular point sticking group at the same time point(all P<0.01);VAS score in the acupuncture group was lower than that in the auricular point sticking group(both P<0.05).At follow-up,the headache frequency in the acupuncture group was lower than that in the auricular point sticking group(P<0.05).Conclusion:Either using acupuncture and auricular point sticking together or separately can reduce the headache degree of TTH patients,reduce the number of headache attacks,and relieve anxiety and depression.The efficacy of acupuncture plus auricular point sticking is most significant.

Clinical Study on Tuina Therapy for Degenerative Spondylolisthesis of the Lumbar Spine

Objective： There is definite therapeutic effect in tuina treating low back pain. The comparative observation was performed on the two types of tuina manipulation for degenerative lumbar spondylolisthesis, in order to explore the best tuina manipulation for lumbar spondylolisthesis. Methods： All of 121 cases with degenerative lumbar spondylolisthesis were divided into the experimental group and control group randomly by the visit orders and pathological gradations, 61 cases in the experimental group, including 34 cases of grade Ⅰ and 27 cases of grade Ⅱ, and 60 in the control group, including 34 cases of grade Ⅰ and 26 cases of grade Ⅱ. There was no significant difference in the general materials of the two groups. Based upon the similar tuina therapy applied on the soft tissues in the two groups, micro-regulating manual technique of the spine was applied in the experimental group, and the hip and knee-flexed and pillow method was applied in the control group. The treatment was given 3 sessions a week, with 10 sessions as one course of the treatments. The therapeutic effects were assessed after one course of the treatments. Results： There was significant difference （P〈0.01） in the total effective rate and in the remarkable effective rate and curative rate of the patients with grade Ⅰ between the experimental group and control group, also there was significant difference （P〈0.05） in the total effective rate of the patients with grade Ⅱ. Conclusions： The therapeutic effects by the micro-regulatory manual technique are comparatively better for degenerative lumbar spondylolisthesis, and the milder the pathological condition is, the better the therapeutic effects would be.