Acquired methemoglobinemia in a third trimester puerpera and her premature infant with sodium nitrite poisoning:A case report

BACKGROUND The common cause of sodium nitrite poisoning has shifted from previous accidental intoxication by exposure or ingestion of contaminated water and food to recent alarming intentional intoxication as an employed method of suicide/exit.The subsequent formation of methemoglobin(MetHb)restricts oxygen transport and utilization in the body,resulting in functional hypoxia at the tissue level.In clinical practice,a mismatch of cyanotic appearance and oxygen partial pressure usually contributes to the identification of methemoglobinemia.Prompt recognition of characteristic mismatch and accurate diagnosis of sodium nitrite poisoning are prerequisites for the implementation of standardized systemic interventions.CASE SUMMARY A pregnant woman was admitted to the Department of Critical Care Medicine at the First Affiliated Hospital of Harbin Medical University due to consciousness disorders and drowsiness 2 h before admission.Subsequently,she developed vomiting and cyanotic skin.The woman underwent orotracheal intubation,invasive mechanical ventilation(IMV),and correction of internal environment disturbance in the ICU.Her premature infant was born with a higher-than-normal MetHb level of 3.3%,and received detoxification with methylene blue and vitamin C,supplemental vitamin K1,an infusion of fresh frozen plasma,as well as respiratory support via orotracheal intubation and IMV.On day 3 after admission,the puerpera regained consciousness,evacuated the IMV,and resumed enteral nutrition.She was then transferred to the maternity ward 24 h later.On day 7 after admission,the woman recovered and was discharged without any sequelae.CONCLUSION MetHb can cross through the placental barrier.Level of MetHb both reflects severity of the sodium nitrite poisoning and serves as feedback on therapeutic effectiveness.

Three-dimensional visualization technology for guiding one-step percutaneous transhepatic cholangioscopic lithotripsy for the treatment of complex hepatolithiasis

BACKGROUND Biliary stone disease is a highly prevalent condition and a leading cause of hospitalization worldwide.Hepatolithiasis with associated strictures has high residual and recurrence rates after traditional multisession percutaneous transhepatic cholangioscopic lithotripsy(PTCSL).AIM To study one-step PTCSL using the percutaneous transhepatic one-step biliary fistulation(PTOBF)technique guided by three-dimensional(3D)visualization.METHODS This was a retrospective,single-center study analyzing,140 patients who,between October 2016 and October 2023,underwent one-step PTCSL for hepatolithiasis.The patients were divided into two groups:The 3D-PTOBF group and the PTOBF group.Stone clearance on choledochoscopy,complications,and long-term clearance and recurrence rates were assessed.RESULTS Age,total bilirubin,direct bilirubin,Child-Pugh class,and stone location were similar between the 2 groups,but there was a significant difference in bile duct strictures,with biliary strictures more common in the 3D-PTOBF group(P=0.001).The median follow-up time was 55.0(55.0,512.0)days.The immediate stone clearance ratio(88.6%vs 27.1%,P=0.000)and stricture resolution ratio(97.1%vs 78.6%,P=0.001)in the 3D-PTOBF group were significantly greater than those in the PTOBF group.Postoperative complication(8.6%vs 41.4%,P=0.000)and stone recurrence rates(7.1%vs 38.6%,P=0.000)were significantly lower in the 3D-PTOBF group.CONCLUSION Three-dimensional visualization helps make one-step PTCSL a safe,effective,and promising treatment for patients with complicated primary hepatolithiasis.The perioperative and long-term outcomes are satisfactory for patients with complicated primary hepatolithiasis.This minimally invasive method has the potential to be used as a substitute for hepatobiliary surgery.

Exploration of transmission chain and prevention of the recurrence of coronavirus disease 2019 in Heilongjiang Province due to inhospital transmission

The coronavirus disease 2019(COVID-19)epidemic is a major public health emergency characterized by fast spread,a wide range of infections,and enormous control difficulty.Since the end of December 2019,Wuhan has become the first core infection area of China's COVID-19 outbreak.Since March 2020,the domestic worst-hit areas have moved to the Heilongjiang Province due to the increased number of imported COVID-19 cases.Herein,we reported the major COVID-19 outbreak,which caused a rebound of the epidemic in Harbin,China.After the rebound,different levels of causes for the recurrence of COVID-19,including citylevel,hospital-level,and medical staff-level cause,were investigated.Meanwhile,corresponding countermeasures to prevent the recurrence of the epidemic were also carried out on the city level,hospital level,and medical staff level,which eventually showed the effect of infection control function in a pandemic.In this study,we described the complete transmission chain,analyzed the causes of the outbreak,and proposed corresponding countermeasures from our practical clinical experience,which can be used as a valuable reference for COVID-19 control.

Tra2βEnhances Cell Proliferation by Inducing the Expression of Transcription Factor SP1 in Cervical Cancer

Objective In this study,the role and potential mechanism of transformer 2β(Tra2β)in cervical cancer were explored.Methods The transcriptional data of Tra2βin patients with cervical cancer from Gene Expression Profiling Interactive Analysis(GEPIA)and cBioPortal databases were investigated.The functions of Tra2βwere evaluated by using Western blot,MTT,colony formation,Transwell assays,and nude mouse tumor formation experiments.Target genes regulated by Tra2βwere studied by RNA-seq.Subsequently,representative genes were selected for RT-qPCR,confocal immunofluorescence,Western blot,and rescue experiments to verify their regulatory relationship.Results The dysregulation of Tra2βin cervical cancer samples was observed.Tra2βoverexpression in Siha and Hela cells enhanced cell viability and proliferation,whereas Tra2βknockdown showed the opposite effect.Alteration of Tra2βexpression did not affect cell migration and invasion.Furthermore,tumor xenograft models verified that Tra2βpromoted cervical cancer growth.Mechanically,Tra2βpositively regulated the mRNA and protein level of SP1,which was critical for the proliferative capability of Tra2β.Conclusion This study demonstrated the important role of the Tra2β/SP1 axis in the progression of cervical cancer in vitro and in vivo,which provides a comprehensive understanding of the pathogenesis of cervical cancer.

Progress and expectation of stem cell therapy for diabetic wound healing

Impaired wound healing presents great health risks to diabetics.Encouragingly,the current clinical successfully found out meaningful method to repair wound tissue,and stem cell therapy could be an effective method for diabetic wound healing with its ability to accelerate wound closure and avoid amputation.This minireview aims at introducing stem cell therapy for facilitating tissue repair in diabetic wounds,discussing the possible therapeutic mechanism and clinical application status and problems.

Multiple sparganosis spinal infections mainly in the thoracic region: A case report

BACKGROUND Spinal infection with sparganosis is rarely seen,and multiple spinal infections with sparganosis in the thoracic spine have not been reported.CASE SUMMARY In this case report,a 56-year old male patient suffered from back pain for 3 mo.Computed tomography examination of the thoracic spine showed bone destruction of the T4-5 vertebral body,as well as the right pedicle and lamina of T5.Magnetic resonance imaging showed high signals on T2W1 images and fat-suppressed images in the right vertebral body of T4-5 and the right pedicle and lamina of T5,a high signal in the vertebral canal,and similar high signals in the paravertebral and subcutaneous regions of the whole spine.Puncture biopsy showed sparganosis.Following definite diagnosis,the patient was treated with debridement of T4-5 infected lesions under a microscope,bone grafting and internal fixation.Postoperatively,the patient's back pain symptoms were significantly relieved;the incision healed after one-stage treatment,and alben-dazole antiparasitic treatment was administered.CONCLUSION Puncture biopsy is the most reliable method to diagnose infection by sparganum.Removal of infected lesions under the microscope and albendazole for anti-parasitic treatment are safe and effective.

Inhibition of VEGF-A expression in hypoxia-exposed fetal retinal microvascular endothelial cells by exosomes derived from human umbilical cord mesenchymal stem cells

Objective:This study aimed to investigate the potential of human umbilical cord mesenchymal stem cell(hucMSC)-derived exosomes(hucMSC-Exos)in inhibiting hypoxia-induced cell hyper proliferation and overexpression of vascular endothelial growth factor A(VEGF-A)in immature human fetal retinal microvascular endothelial cells(hfRMECs).Methods:Exosomes were isolated from hucMSCs using cryogenic ultracentrifugation and characterized through various techniques,including transmission electron microscopy,nanoparticle tracking analysis,bicinchoninic acid assays,and western blotting.The hfRMECs were identified using von Willebrand factor(vWF)co-staining and divided into four groups:a control group cultured under normoxic condition,a hypoxic model group,a hypoxic group treated with low-concentration hucMSC-Exos(75μg/mL)and a hypoxic group treated with high-concentration hucMSC-Exos(100μg/mL).Cell viability and proliferation were assessed using Cell Counting Kit-8(CCK-8)assay and EdU(5-ethynyl-2′-deoxyuridine)assay respectively.Expression levels of VEGF-A were evaluated using RT-PCR,western blotting and immunofluorescence.Results:Hypoxia significantly increased hfRMECs’viability and proliferation by upregulating VEGF-A levels.The administration of hucMSC-Exos effectively reversed this response,with the high-concentration group exhibiting greater efficacy compared to the lowconcentration group.Conclusion:In conclusion,hucMSC-Exos can dose-dependently inhibit hypoxia-induced hyperproliferation and VEGF-A overexpression in immature fetal retinal microvascular endothelial cells.

Prognostic value of the long noncoding RNA AFAP1-AS1 in cancers

Objective This meta-analysis explored whether the expression of actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1)is related to the prognosis and clinicopathological features of patients with cancer.Methods PubMed,EMBASE,and Cochrane Library were systematically searched.Hazard ratios(HRs)with 95%confidence intervals(CIs)were used to assess the prognostic value based on overall survival(OS),disease-free survival(DFS),and progression-free survival(PFS).Odds ratios(ORs)with 95%CIs were used to determine the relationships between AFAP1-AS1 and clinicopathological features,such as large tumor size(LTS),high tumor stage(HTS),poor histological grade(PHG),lymph node metastasis(LNM),and distant metastasis(DM).Results Thirty-five eligible articles and 3433 cases were analyzed.High AFAP1-AS1 expression,compared to low AFAP1-AS1 expression,correlated with significantly shorter OS(HR=2.15,95%CI=1.97-2.34,P<0.001),DFS(HR=1.37,95%CI=1.19-1.57,P<0.001),and PFS(HR=1.97,95%CI=1.56-2.50,P<0.001)in patients with cancer.In various cancers,elevated AFAP1-AS1 expression was significantly associated with LTS(OR=2.76,95%CI=2.16-3.53,P<0.001),HTS(OR=2.23,95%CI=1.83-2.71,P<0.001),and PHG(OR=1.39,95%CI=1.08-1.79,P=0.01)but not LNM(OR=1.59,95%CI=0.88-2.85,P=0.12)or DM(OR=1.81,95%CI=0.90-3.66,P=0.10).Conclusion High AFAP1-AS1 expression was associated with prognostic and clinicopathological features,suggesting that AFAP1-AS1 is a prognostic biomarker for human cancers.

The Clinical Outcomes of Mosaic Embryo Transfer in Preimplantation Genetic Testing Cycles

Purpose: We aimed to analyze the pregnancy outcomes and perinatal follow-up of mosaic embryo transfer in the preimplantation genetic testing (PGT) cycles. Method: We retrospectively selected 27 mosaic embryo transfer cycles as the study group and 97 euploid embryo transfer cycles as the control group after propensity score matching, which were performed in the reproductive medicine center of the Sixth Affiliated Hospital, Sun Yat-sen University, from March 2019 to September 2023. The biopsy cells from blastocyst were undertaken next generation sequencing (NGS). Results: No significant difference in pregnancy outcomes compared between the two groups. According to the size of aneuploid, fragment the level of mosaicism or blastocyst morphological gradings, there were no significant difference in mosaic embryo transfers. Conclusion: Mosaic embryo detected in the PGT cycle can lead to clinical pregnancy and live birth of healthy offspring, which can be considerate suitable for transfer.

Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

Effectivity and safety of trifocal intraocular lenses and capsular tension rings implantation for cataract patients with axial high myopia

●AIM:To assess effectivity and safety of trifocal intraocular lenses(IOLs)and capsular tension rings in treating cataract patients with axial high myopia.●METHODS:A prospective nonrandomized controlled clinical trial was conducted.Totally 98 eyes(74 patients)who underwent femtosecond laser-assisted cataract surgery(FLACS)with trifocal IOLs were enrolled in the study and followed up for 2y after surgery:46 eyes(33 patients)with capsular tension ring implantation in the long axial lengths(AL)group(26<AL<29 mm)and 52 eyes(41 patients)in the normal AL group(22<AL<24.5 mm).Postoperative outcomes about effectivity and safety,including the subjective and objective visual quality,and postoperative complications were assessed.●RESULTS:Uncorrected distance visual acuity at 5 m and uncorrected intermediate visual acuity at 60 and 80 cm in the long AL group were significantly worse than those in the normal AL group at 3mo postoperatively(P<0.05).The differences in reading speed,spectacle independence and potential visual complaints between the two groups were not statistically significant(P>0.05).The dysfunctional lens index and total modulation transfer function(MTF)average height were similar between the two groups.The postoperative internal coma aberrations in the axial high myopia eyes were significantly higher than that in the normal AL group(P<0.05).The total satisfaction score in the long AL group(91.32±2.76)was slightly higher than that in the normal AL group(90.36±3.47),but there was no difference(P=0.136).A statistically negative correlation was found between corrected distance visual acuity(CDVA)and dysfunctional lens index(r=-0.382,P=0.009),and between CDVA and the total MTF average height(r=-0.374,P=0.01).But there was no significant correlation between CDVA and total satisfaction score(r=0.059,P=0.696).Postoperative complications mainly presented as posterior capsular opacity(PCO),retinal detachment and cystoid macular edema.There was no difference in the incidence of fundus disease(6.5%vs 3.8%,P=0.663)or PCO(17.4%vs 7.7%,P=0.217)between the two groups at two years.●CONCLUSION:The utilization of trifocal IOL and capsular tension ring implantation is beneficial for cataract patients with axial high myopia undergoing FLACS.This approach not only ensures excellent subjective feelings and objective visual quality,but also does not increase the incidence of postoperative complications.

Early proactive monitoring of DNA-thioguanine in patients with Crohn’s disease predicts thiopurine-induced late leucopenia in NUDT15/TPMT normal metabolizers

BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there are no definitive biomarkers for late risk leucopenia prediction.AIM To determine the predictive value of early monitoring of DNA-thioguanine(DNATG)or 6-thioguanine nucleotides(6TGN)for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn’s disease(CD).METHODS Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations.Late leucopenia was defined as a leukocyte count<3.5×10^(9)/L over two months.RESULTS Of 148 patients studied,late leucopenia was observed in 15.6%(17/109)of NUDT15/thiopurine methyltransferase(TPMT)normal and 64.1%(25/39)of intermediate metabolizers.In patients suffering late leucopenia,early DNATG levels were significantly higher than in those who did not develop late leucopenia(P=4.9×10^(-13)).The DNATG threshold of 319.43 fmol/μg DNA could predict late leucopenia in the entire sample with an area under the curve(AUC)of 0.855(sensitivity 83%,specificity 81%),and in NUDT15/TPMT normal metabolizers,the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902(sensitivity 88%,specificity 85%).6TGN had a relatively poor correlation with late leucopenia whether in the entire sample(P=0.021)or NUDT15/TPMT normal or intermediate metabolizers(P=0.018,P=0.55,respectively).CONCLUSION Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD,especially the former.

Predictive factors for the local recurrence and distant metastasis of phyllodes tumors of the breast: a retrospective analysis of 192 cases at a single center

The local recurrence rate of phyllodes tumors of the breast varies widely among different subtypes, and distant metastasis is associated with poor survival. This study aimed to identify factors that are predictive of local recurrence-free survival(LRFS), distant metastasis-free survival(DMFS), and overall survival(OS) in patients with phyllodes tumors of the breast. Clinical data of all patients with a phyllodes tumor of the breast(n = 192) treated at Sun Yat-sen University Cancer Center between March 1997 and December 2012 were reviewed. The Pearson χ2 test was used to investigate the relationship between clinical features of patients and histotypes of tumors. Univariate and multivariate Cox regression analyses were performed to identify factors that are predictive of LRFS, DMFS, and OS. In total, 31(16.1%) patients developed local recurrence, and 12(6.3%) developed distant metastasis. For the patients who developed local recurrence, the median age at the diagnosis of primary tumor was 33 years(range, 17-56 years), and the median size of primary tumor was 6.0 cm(range, 0.8-18 cm). For patients who developed distant metastasis, the median age at the diagnosis of primary tumor was 46 years(range, 24-68 years), and the median size of primary tumor was 5.0 cm(range, 0.8-18 cm). In univariate analysis, age, size, hemorrhage, and margin status were found to be predictive factors for LRFS(P = 0.009, 0.024, 0.004, and 0.001, respectively), whereas histotype, epithelial hyperplasia, margin status, and local recurrence were predictors of DMFS(P = 0.001, 0.007, 0.007, and < 0.001, respectively). In multivariate analysis, independent prognostic factors for LRFS included age [hazard ratio(HR) = 3.045, P = 0.005], tumor size(HR = 2.668, P = 0.013), histotype(HR = 1.715, P = 0.017), and margin status(HR = 4.530, P< 0.001). Histotype(DMFS: HR = 4.409, P = 0.002; OS: HR = 4.194, P = 0.003) and margin status(DMFS: HR = 2.581, P = 0.013; OS: HR = 2.507, P = 0.020) were independent predictors of both DMFS and OS. In this cohort, younger age, a larger tumor size, a higher tumor grade, and positive margins were associated with lower rates of LRFS. Histotype and margin status were found to be independent predictors of DMFS and OS.

Long-term outcomes of a phase Ⅱ randomized controlled trial comparing intensity-modulated radiotherapy with or without weekly cisplatin for the treatment of locally recurrent nasopharyngeal carcinoma

Background:Salvage treatment for locally recurrent nasopharyngeal carcinoma(NPC) is complicated and relatively limited.Radiotherapy,combined with effective concomitant chemotherapy,may improve clinical treatment outcomes.We conducted a phase Ⅱ randomized controlled trial to evaluate the efficacy of intensity-modulated radiotherapy with concomitant weekly cisplatin on locally recurrent NPC.Methods:Between April 2002 and January 2008,69 patients diagnosed with non-metastatic locally recurrent NPC were randomly assigned to either concomitant chemoradiotherapy group(n = 34) or radiotherapy alone group(n = 35).All patients received intensity-modulated radiotherapy.The radiotherapy dose for both groups was 60 Gy in 27 fractions for 37 days(range 23-53 days).The concomitant chemotherapy schedule was cisplatin 30 mg/m^2 by intravenous infusion weekly during radiotherapy.Results:The median follow-up period of all patients was 35 months(range 2-112 months).Between concomitant chemoradiotherapy and radiotherapy groups,there was only significant difference in the 3-year and 5-year overall survival(OS) rates(68.7%vs.42.2%,P = 0.016 and 41.8%vs.27.5%,P = 0.049,respectively).Subgroup analysis showed that concomitant chemoradiotherapy significantly improved the 5-year OS rate especially for patients in stage rT3-4(33.0%vs.13.2%,P = 0.009),stages Ⅲ-Ⅳ(34.3%vs.13.2%,P = 0.006),recurrence interval >30 months(49.0%vs.20.6%,P = 0.017),and tumor volume >26 cm^3(37.6%vs.0%,P = 0.006).Conclusion:Compared with radiotherapy alone,concomitant chemoradiotherapy can improve OS of the patients with locally recurrent NPC,especially those with advanced T category(rT3-4) and stage(lll-IV) diseases,recurrence intervals >30 months,and tumor volume >26 cm^3.

Risk factors for sporadic colorectal cancer in southern Chinese

AIM:To investigate the role of smoking, alcohol drinking, family history of cancer, and body mass index(BMI) in sporadic colorectal cancer in southern Chinese.METHODS:A hospital-based case-control study was conducted from July 2002 to December 2008.There were 706 cases and 723 controls with their sex and age(within 5 years) matched.An unconditional logistic regression model was used to analyze the association between smoking, alcohol drinking, family history of cancer, BMI and sporadic colorectal cancer.RESULTS:No positive association was observed between smoking status and sporadic colorectal cancer risk.Compared with the non alcohol drinkers, the current and former alcohol drinkers had an increased risk of developing sporadic colorectal cancer(CRC)(adjusted OR = 8.61 and 95% CI = 6.15-12.05;adjusted OR = 2.30, 95% CI = 1.27-4.17).Moreover, the increased risk of developing sporadic CRC was significant in those with a positive family history of cancer(adjusted OR = 1.62, 95% CI = 1.12-3.34) and in those with their BMI ≥ 24.0 kg/m2(adjusted OR = 1.39, 95% CI = 1.10-1.75).Stratification analysis showed that the risk of developing both colon and rectal cancers was increased in current alcohol drinkers(adjusted OR = 7.60 and 95% CI = 5.13-11.25;adjusted OR = 7.52 and 95% CI = 5.13-11.01) and in those with their BMI ≥ 24.0 kg/m2(adjusted OR = 1.38 and 95% CI = 1.04-1.83;adjusted OR = 1.35 and 95% CI = 1.02-1.79).The risk of developing colon cancer, but not rectal cancer, was found in former alcohol drinkers and in those with a positive family history of cancer(adjusted OR = 2.51 and 95% CI = 1.24-5.07;adjusted OR = 1.82 and 95% CI = 1.17-2.82).CONCLUSION:Alcohol drinking, high BMI(≥ 24.0 kg/m2) and positive family history of cancer are the independent risk factors for colorectal cancer in southern Chinese.

5-Fluorouracil upregulates the activity of Wnt signaling pathway in CD133-positive colon cancer stem-like cells

Background and Objective:CD133-positive colon cancer stem like cells (CSLCs) are resistant to the conventional cytotoxic drug 5-fluorouracil (5-FU).Wnt signaling pathway plays important roles in colon cancer carcinogenesis and metastasis, and regulates the self-renewal capacity of CSLCs.In the present study, we explored the impact of 5-FU on Wnt signaling pathway of CD133-positive colon CSLCs, and the relation between Wnt signaling pathway and drug resistance of CD133-positive colon CSLCs.Methods:Magnetic activation cell separation was used to collect CD133-positive cells from colon cancer cell line DLD1, which was transfected with luciferase reporter for Wnt signaling activity.The activity of Wnt signaling pathway was compared between CD133-positive and CD133-negative cells.After the treatment with 1 μg/mL of 5-FU, the cell proliferation rates of DLD1 cells, CD133-positive cells, and CD133-negative cells were compared.After the treatment with 1 μg/mL and 10 μg/mL of 5-FU for 48 h, Wnt activity was compared between CD133-positive and CD133-negative cells.The expression of CD133 and cell apoptosis of CD133-positive cells was detected after exposure to 50 ng/mL of dickkopf (DKK)-1, a Wnt pathway inhibitor.Results:After the treatment with 5-FU, the cell proliferation rate of CD133-positive cells was higher than that of CD133-negative cells and the sensitivity of CD133-positive cells to 5-FU decreased.Wnt activity was higher in CD133-positive cells than in CD133-negative cells [(46.3±0.3)% vs.(33.9±2.7)%, P=0.009].After the treatment with 1 μg/mL and 10 μg/mL of 5-FU, Wnt activity of CD133-positive cells was (90.1±10.0)% (P=0.012) and (52.9±2.5)% (P=0.047), respectively, whereas that of CD133-negative cells was (35.5±3.3)% (P=0.434) and (26.5±0.4)% (P=0.046), respectively.CD133 expression in CD133-positive cells decreased from (87.2±5.3)% to (60.6±3.1)% (P=0.022) after treatment with DKK-1, whereas the cell apoptosis rate increased from (11.8±0.2)% to (28.3±0.6)% (P=0.013).Conclusions:Wnt activity is higher in CD133-positive DLD1 cells than in CD133-negative DLD1 cells.5-FU can upregulate Wnt activity of CD133-positive colon CSLCs.Blocking Wnt activity may reverse drug sensitivity of CD133-positive cells to 5-FU.

New therapeutic options for persistent low-level viremia in patients with chronic hepatitis B virus infection:Increase of entecavir dosage

Chronic hepatitis B virus(HBV)infection(CHB)is a public health concern worldwide.Current therapies utilizing nucleos(t)ide analogs(NA)have not resulted in a complete cure for CHB.Furthermore,patients on long-term NA treatment often develop low-level viremia(LLV).Persistent LLV,in addition to causing the progression of liver disease or hepatocellular carcinoma,may shed light on the current plight of NA therapy.Here,we review the literature on LLV,NA treatment,and various doses of entecavir to find a strategy for improving the efficacy of this antiviral agent.For LLV patients,three therapeutic options are available,switching to another antiviral monotherapy,interferon-αswitching therapy,and continuing monotherapy.In real-world clinical practice,entecavir overdose has been used in antiviral therapy for CHB patients with NA refractory and persistent LLV,which encouraged us to conduct further in-depth literature survey on dosage and duration related entecavir studies.The studies of pharmacodynamics and pharmacokinetics show that entecavir has the maximal selected index for safety,and has great potential in inhibiting HBV replication,in all of the NAs.In the particular section of the drug approval package published by the United States Food and Drug Administration,entecavir doses 2.5-20 mg/d do not increase adverse events,and entecavir doses higher than 1.0 mg/d might improve the antiviral efficacy.The literature survey led us to two suggestions:(1)Increasing entecavir dose to 1.0 mg/d for the treatment of NA naïve patients with HBV DNA>2×106 IU/mL is feasible and would provide better prognosis;and(2)Further research is needed to assess the long-term toxic effects of higher entecavir doses(2.5 and 5.0 mg/d),which may prove beneficial in treating patients with prior NA treatment,partial virological response,or LLV state.

In vitro and In vivo Evaluation of the Developed PLGA/HAp/Zein Scaffolds for Bone-Cartilage Interface Regeneration

Objective To investigate the effect of electronspun PLGA/HAp/Zein scaffolds on the repair of cartilage defects. Methods The PLGA/HAp/Zein composite scaffolds were fabricated by electrospinning method. The physiochemical properties and biocompatibility of the scaffolds were separately characterized by scanning electron microscope （SEM）, transmission electron microscope （TEM）, and fourier transform infrared spectroscopy （FTIR）, human umbilical cord mesenchymal stem cells （hUC-MSCs） culture and animal experiments. Results The prepared PLGA/HAp/Zein scaffolds showed fibrous structure with homogenous distribution, hUC-MSCs could attach to and grow well on PLGA/HAp/Zein scaffolds, and there was no significant difference between cell proliferation on scaffolds and that without scaffolds （P〉0.05）. The PLGA/HAp/Zein scaffolds possessed excellent ability to promote in vivo cartilage formation. Moreover, there was a large amount of immature chondrocytes and matrix with cartilage lacuna on PLGA/HAp/Zein scaffolds. Conclusion The data suggest that the PLGA/HAp/Zein scaffolds possess good biocompatibility, which are anticipated to be potentially applied in cartilage tissue engineering and reconstruction.

Nomogram for predicting pathological complete response to neoadjuvant chemotherapy in patients with advanced gastric cancer

BACKGROUND Survival benefit of neoadjuvant chemotherapy(NAC)for advanced gastric cancer(AGC)is a debatable issue.Studies have shown that the survival benefit of NAC is dependent on the pathological response to chemotherapy drugs.For those who achieve pathological complete response(pCR),NAC significantly prolonged prolapsed-free survival and overall survival.For those with poor response,NAC yielded no survival benefit,only toxicity and increased risk for tumor progression during chemotherapy,which may hinder surgical resection.Thus,predicting pCR to NAC is of great clinical significance and can help achieve individualized treatment in AGC patients.AIM To establish a nomogram for predicting pCR to NAC for AGC patients.METHODS Two-hundred and eight patients diagnosed with AGC who received NAC followed by resection surgery from March 2012 to July 2019 were enrolled in this study.Their clinical data were retrospectively analyzed by logistic regression analysis to determine the possible predictors for pCR.Based on these predictors,a nomogram model was developed and internally validated using the bootstrap method.RESULTS pCR was confirmed in 27 patients(27/208,13.0%).Multivariate logistic regression analysis showed that higher carcinoembryonic antigen level,lymphocyte ratio,lower monocyte count and tumor differentiation grade were associated with higher pCR.Concordance statistic of the established nomogram was 0.767.CONCLUSION A nomogram predicting pCR to NAC was established.Since this nomogram exhibited satisfactory predictive power despite utilizing easily available pretreatment parameters,it can be inferred that this nomogram is practical for the development of personalized treatment strategy for AGC patients.

Chidamide based combination regimen for treatment of monomorphic epitheliotropic intestinal T cell lymphoma following radical operation:Two case reports

BACKGROUND Monomorphic epitheliotropic intestinal T cell lymphoma(MEITL)is a rare extranodal T-cell lymphoma that has uniformly aggressive features with a poor prognosis.No standardized treatment protocols have been established.Previous experience has demonstrated favorable outcomes with combination chemotherapy followed by autologous hematopoietic stem cell transplant.However,many patients are unable to tolerate the toxicities.Chidamide is a new histone deacetylase inhibitor that has shown preferential efficacy in mature T-cell lymphoma.CASE SUMMARY We herein present two cases of MEITL who were both intermediate risk according to enteropathy-associated T cell lymphoma prognostic index.Case one was a 61-year-old man.He complained of upper abdominal pain and intermittent black stool for 2 mo.Imaging examination revealed that the intestinal wall was thickened.He received a partial excision of the small intestine.A chidamidebased combination regimen was given postoperatively.Eleven months later,he presented with recurrence in the bilateral lungs.He passed away 15 mo after his diagnosis.Case two was a 35-year-old woman who complained of abdominal distention for 1 mo.Positron emission tomography/computed tomography demonstrated wall thickening of the small intestine and upper sigmoid colon.Colon perforation and septic shock occurred on the fourth day of her admission.She was treated by sigmoid colostomy.Chidamide-based combination therapy was then provided.She was recurrence-free for 6 mo until lesions were found in the bilateral brain and lived for 17 mo since her diagnosis.Compared to historical data,chidamide seems to improve the prognosis of MEITL slightly.CONCLUSION MEITL is a type of aggressive lymphoma.Chidamide is a new promising approach for the treatment of MEITL.