OBJECTIVE To analyze the safety and efficacy of vonoprazan （VPZ） in the treatment of peptic ulcer （PU） and post-endoscopic submucosal dissection （ESD） ulcers， providing evidence-based pharmaceutical evidence for clinical practice and medical decision-making. METHODS Retrieved from CNKI， Wanfang， VIP， CBM， PubMed， Embase， Web of Science， and the Cochrane Library， meta-analyses/systematic reviews related to VPZ in the treatment of PU and post-ESD ulcers were collected. Two researchers independently performed literature screening， data extraction， quality assessment of included studies， and evaluation of literature overlap. By employing the umbrella review analysis， a fresh meta-analysis was conducted on all relevant raw research data when a high degree of overlap was identified among the included studies. RESULTS A total of 17 meta-analyses were included， with quality ranging from high to very low； all outcome measures involved showed a very high level of overlap in the included meta-analyses （corrected covered area： 22.22%-100%）. In the treatment of post-ESD ulcers， compared to proton pump inhibitor （PPI）， VPZ significantly improved the ulcer healing rate at 4 weeks post-ESD [RR＝1.27， 95%CI （1.03， 1.56）， Z＝2.21， P＝ 0.027] and the ulcer contraction rate post-ESD [MD＝0.08， 95%CI （0.00， 0.16）， Z＝2.09， P＝0.037]， while significantly reducing the ulcer recurrence rate in patients with a history of PU [RR＝0.49， 95%CI （0.32， 0.73）， Z＝3.49， P＝0.001]； the delayed bleeding rate in the VPZ group was significantly lower than that in the lansoprazole subgroup [RR＝0.47， 95%CI （0.25， 0.90）， Z＝2.28， P＝0.02]. In the treatment of PU， the incidence of adverse events with VPZ was significantly higher than that with PPI in the duodenal ulcer subgroup [RR＝1.13， 95%CI （1.02， 1.26）， Z＝2.38， P＝0.017]. CONCLUSIONS For post-ESD ulcers， VPZ demonstrates superior therapeutic efficacy compared to PPI and can reduce ulcer recurrence rates in patients with a history of PU. However， it does not offer advantages in terms of safety for duodenal ulcer treatment.

ObjectiveTo investigate how vitamin B₁₂ eye drops regulate MMP-9 and TNF-α expression levels in the corneas of dry eye disease （DED） mouse model induced by a combination of an artificially simulated dry environment （air humidity 30%） and subcutaneous injection of hyoscine hydrobromide. MethodsFifty C57BL/6 female mice were used in the study. 10 mice formed A group （blank control）， while the remaining 40 mice were subjected to dry eye disease induction through subcutaneous injection of scopolamine hydrobromide in a controlled environment with 30% air humidity. All mice underwent schirmer I test （SIT）， tear break-up time （TBUT）， and corneal fluorescence staining score（CFS）evaluations. Mice meeting modeling criteria were randomly assigned to three groups： B group （model group）， C group （PBS control）， and D group （vitamin B₁₂ group）. 0， 7， 14， and 21 days after treatment， each group received TBUT， SIT， CFS， and corneal inflammation assessments. Macroscopic analysis evaluated the efficacy of vitamin B₁₂ eye drops in treating dry eye. After 21 days of treatment， all mice were euthanized via cervical dislocation and their corneas analyzed using HE staining to examine morphological changes. ELISA and immunohistochemical methods were employed to detect MMP-9 and TNF-α expression levels in corneal tissues across groups. ResultsIn dry environments （air humidity 30%）， subcutaneous injection of scopolamine hydrobromide induced changes in dry eye-related indicators in mice： SIT significantly decreased， TBUT significantly shortened， corneal fluorescein staining increased， and CFS all significantly elevated （P 0.05）， indicating successful establishment of the dry eye model. A total of 30 dry eye mice were enrolled. When the dry eye model was successfully established without drug intervention， no statistically significant differences were observed between B group， C group and D group in terms of TBUT， SIT， corneal fluorescein staining， or CFS. Compared with A group， B group， C group and D group showed statistically significant differences in reduced SIT， shortened TBUT， increased corneal fluorescein staining， and elevated CFS （P 0.05）. After drug intervention， D group （vitamin B₁₂ group） exhibited significantly increased SIT， prolonged TBUT， reduced corneal fluorescein staining， clearer corneas， decreased fluorescein staining， and lower CFS compared with B and C groups（P 0.05）. ELISA and immunohistochemical staining results showed that compared with A group， B and C groups exhibited significantly increased expression of MMP-9 and TNF-α in corneal tissues （P 0.05）. D group showed decreased expression of MMP-9 and TNF-α compared with B and C groups but remained higher than A group （P 0.05）. ConclusionThe expression of MMP-9 and TNF-α in the corneal tissues of mice with dry eye is elevated， suggesting that both inflammatory factors， MMP-9 and TNF-α， are involved in the development of dry eye. Vitamin B₁₂ eye drops may improve the symptoms of ocular surface discomfort by promoting the repair of the corneal epithelium. Vitamin B₁₂ eye drops may increase tear secretion， prolong tear film break up time， reduce corneal fluorescein staining， and alleviate the inflammatory reaction of the cornea by decreasing the expression of MMP-9 and TNF-α in the corneal tissues of the mice， thus playing a therapeutic role in the treatment of dry eye disease.

Objectives:This study aims to explore the impact of new-onset heart conduction block post transcatheter aortic valve replacement(TAVR)on the cardiac conduction status during 1-year follow-up.Methods:A total of 130 patients who completed TAVR surgery at Fuwai Central-China Cardiovascular Hospital from July 2019 to October 2022 were screened.Among them,56 cases with postoperative heart conduction block were selected for analysis.According to the degree of heart block,patients were divided into mild block group(n=36),moderate block group(n=9),and severe block group(n=11).The clinical characteristics and cardiac conduction conditions at 1-year follow-up between different groups were compared.Results:During a mean(8.5±4.1)months follow-up period,10(17.9%)patients had long-term atrioventricular conduction block,and 46(82.1%)patients had partial or complete recovery of heart block,with 28(50.0%)patients with completely recovered cardiac conduction.In the mild block group,22(61.1%)cases were completely recovered,9(25.0%)patients partly recovered,and 5(13.9%)cases uncovered.In the moderate block group,2(22.2%)cases were completely recovered,5(55.6%)patients partly recovered,and 2(22.2%)cases uncovered.Difference in long-term atrioventricular conduction block among three groups was statistically significant(P<0.001).The Kaplan-Meier curve shows that patients with moderate to severe heart block have a higher rate of long-term atrioventricular conduction block(86.1%vs.77.8%vs.72.7%,log-rank P=0.03).Cox multivariate analysis exhibited that old age(≥75 years old,HR=1.204,95%CI:1.051-1.525,P=0.041)and severe heart conduction block(HR=1.106,95%CI:1.100-1.616,P=0.031)are the two independent risk factors for long-term atrioventricular conduction block post TAVR.Conclusions:The ratio of complete cardiac conduction recovery post TAVR is 50.0%.Older age(≥75 year)and new-onset severe heart conduction block are independent risk factors for long-term atrioventricular conduction block post TAVR procedure.

Plant virus nanoparticles(PVNPs)have inherent immune stimulation ability,which has been widely studied as an immune adjuvant to stimulate the anti-tumor immune response.PVNPs not only have the potential to be used as vaccine adjuvants for cancer immunotherapy,but also as delivery systems for single immunotherapy or combination therapies.Among them,PVNPs have achieved great success in preclinical research of cancer immunotherapy.The new immunotherapy strategy is to use PVNPs as in situ vaccination(ISV),which can effectively inhibit tumor growth and produce a widening systemic anti-tumor immune response after in-tratumoral administration;in addition,PVNPs in combination with other tumor treatment modalities may also improve the local and systemic anti-tumor immune response.In this review,the application and prospects of plant virus nanoparticles in cancer immunotherapy are reviewed,in order to provide new ideas for cancer immunotherapy.

Objective:To investigate the influence of cytochrome P450 2A6 (CYP2A6) gene polymorphisms on liver function injury in patients with hyperthyroidism treated with methimazole.Methods:The study selected 90 patients with hyperthyroidism who were treated with methimazole in the Department of Thyroid Surgery at the First Affiliated Hospital of Zhengzhou University from Sept. 2023 to Aug. 2024 as the research subjects. Based on the occurrence of liver injury, they were divided into a liver injury group ( n=36) and a non-liver injury group (n=54). Peripheral blood DNA was extracted from the patients, and the CYP2A6 gene genotypes (rs8192725, rs8192720, and rs28399433) were detected using the polymerase chain reaction (PCR) amplification method. The association between CYP2A6 gene polymorphisms and liver injury induced by methimazole treatment in hyperthyroidism was analyzed. Results:The comparison of genotype distribution frequencies at the rs8192725 locus between the liver injury group and the non-liver injury group showed a statistically significant difference ( P<0.05). The AG and GG genotypes at the rs8192725 locus were protective factors against liver injury in patients with hyperthyroidism (AG vs. AA, OR: 0.21; 95% CI: 0.08-0.57; P<0.05; GG vs. AA, OR: 0.24; 95% CI: 0.06-0.89; P<0.05; AG+GG vs. AA, OR: 0.22; 95% CI: 0.09-0.54; P<0.05). The frequency of the G allele of rs8192725 in the liver injury group was significantly lower than that in the non-liver injury group (G vs. A, OR: 0.36; 95% CI: 0.19-0.70; P<0.05), indicating that it is a protective factor for liver injury in hyperthyroid patients receiving methimazole treatment. Conclusions:The CYP2A6 gene polymorphism at the rs8192725 locus is associated with the occurrence of liver injury in patients with hyperthyroidism treated with methimazole. The G allele may be a protective factor against liver injury in patients with hyperthyroidism, suggesting that individualized treatment plans can be developed based on the patient's genotype.

Objective:To explore the evaluation and relationship of hepatitis B virus(HBV)surface antigen(HBsAg)in clinical laboratory in different detection systems,further scientifically and reasonably to explain the test results for serving clinical practices.Methods:During the period from June 2021 to July 2022,100 425 specimens of patients with screened,suspected and confirmed HBV infections were collected from the clinical departments(mainly infectious hepatology)of Nanyang Central Hospital.Detection methodology included quantitative(electrochemiluminescence and chemiluminescence),qualitative(gold standard),semi-quantita-tive(ELISA),and highly sensitive HBV-DNA(RT-PCR)methods,and then analyzed the strengths and weaknesses and closeness be-tween each methodology.The relationship between the two Roche HBsAg detection systems was analyzed by correlation analysis.The HBsAg efficacy analysis was validated using Cut/Off value setting and detection limit,which in turn analyzed the distribution of false-positive and false-negative reporting models.Results:Detection results for low-and medium-concentration HBsAg showed a correla-tion between the electrochemical luminescence semi-quantitative method and ELISA method.ELISA method still had advantages in terms of sensitivity and specificity when detecting HBsAg,and there were no significant differences compared to domestic and interna-tional HBsAg quantitative detection systems.Performance validation conducted in accordance with the CNAS-GL038 document showed that the minimum detection limit for HBsAg calculated using the ELISA method in this laboratory was 0.1 U/ml.When the ROC curve Cut/Off value was set to 0.105,the area under the curve was the largest(AUC=0.986).Based on Roche's semi-quantitative electroche-miluminescence detection and patient medical history,in the common reporting model for hepatitis B five-item detection using ELISA method,HBsAg false positives occurred most frequently when HBsAg was positive alone,and HBsAg occurred most frequently in the false positive range when the OD value was less than 0.5.In ELISA method for detecting HBsAg,as the OD value increased from 0.01 to 0.10,the number of false-negative results also increased.Roche Elecsys HBsAg Ⅱ Quant Ⅱ and Elecsys HBsAg Ⅱ testing systems exhibited good linearity under certain conditions,with a ratio of approximately 1/0.18.In Elecsys HBsAg Ⅱ Quant Ⅱ detection sys-tem,the test results of HBsAg samples diluted 400 times were highly consistent with the original test results with a coefficient of deter-mination R2=0.993 8.Conclusion:There was a certain relationship between various detection systems of HBsAg at a suitable concen-tration.The detection of HBsAg by ELISA can meet the needs of clinical detection.

Objective:To explore the feasibility of joint screening of the two primary immunodeficiency diseases [severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia(XLA)] and spinal muscular atrophy(SMA) in newborns by multiplex real-time quantitative PCR technology, and to provide evidence for early screening, diagnosis and treatment of children.Methods:Cross-sectional study. From July 2021 to January 2023, a total of 103 240 dry blood spots samples of newborns were collected which were delivered to Neonatal Disease Screening Center of Zhejiang by cold chain transportation. The concentrations of the T cell receptor excision ring (TREC), Kappa deletion of the recombinant excision loop (KREC), and exon 7 deletion of Survival Motor Neuron 1 (SMN1) gene in dry blood spots were simultaneously detected by multiplex real-time fluorescence quantitative PCR, taken ribonuclease P/MRP 30 000 subunits (RPP30) as an internal reference gene. The positive newborns were further diagnosed by other laboratory tests and gene sequencing was taken as gold standard. Children samples from 1 case of SCID, 3 cases of XLA and 2 cases of SMA were used for positive verification. The correlation between detected concentration of TREC/KREC and basic information in newborns were analyzed. The differences among groups for each factor were analyzed.Results:One case of SCID, 2 cases of XLA, 9 cases of SMA and 7 cases of other genetic diseases (4 cases of DiGeorge syndrome, 1 case of trisomy 21 syndrome, 1 case of Noonan syndrome and 1 case of super male syndrome) were identified by multiplex real-time fluorescence quantitative PCR. The positive predictive values of screening neonatal SCID, XLA and SMA were 2.44% (1/41), 2.78% (2/72) and 9/9 respectively. Taking the samples from clinically diagnosed 1 case of SCID, 3 cases of XLA and 2 cases of SMA as positive validation samples, which were all identified. The detected results of TREC/KREC correlated with time of blood collection, sex, weight, gestational age and delivery mode of newborns, whose r values were 0.162/0.187, 0.066/0.032, 0.045/0.042, ?0.015/?0.088 and 0.014/0.068 respectively (all P<0.05). Conclusions:Relying on current neonatal screening platform in Zhejiang, it is feasible to screen jointly two kinds of primary immunodeficiency diseases and spinal muscular atrophy in newborns by multiple real-time fluorescence quantitative PCR technology.

Objective:To investigate the methodological differences in the detection, the inflammatory markers and the pathogenic epidemiological characteristics of influenza A virus in clinical laboratories, in order to provide more diagnostic and epidemiological data for diagnosis and prevention for children with influenza A.Methods:A retrospective cross-sectional study was conducted to collect 96 731 patients with suspected influenza A from January 2016 to October 2024 in Nanyang City Center Hospital from the Clinical Laboratory Testing Information System, including 5 731 patients with confirmed influenza A, aged 5.2 (2.8, 43.7) years old. We analyzed the distribution of influenza A patients from age and mixed infections, the relationship between patient age and positive detection rate by restricted cubic spline (RCS), analyzed differences in testing methods used Kappa consistency testing and receiver operating characteristic (ROC) curves, established a model of inflammatory markers by logistic regression, as well as developed a prediction model and also the mutation of the hemagglutinin (HA) sequence of the influenza A subtype H3N2 virus using evolutionary tree analysis.Results:RCS analysis showed an inverted 'S' shaped non-linear relationship between the positive detection rate of influenza A and the age groups of the patients. Among the mixed infections, 1.43%(1 352/94 867) of the cases were combined with Mycoplasma pneumoniae infection. The Kappa values of reverse transcription PCR (RT-PCR) and serological indirect immunofluorescence assay (IFA) for detecting influenza A in nasopharyngeal swabs and alveolar lavage fluid in clinical laboratories were 0.632 and 0.809, respectively, and those of magnetic particle chemiluminescence assay were 0.614 and 0.668, respectively, and the area under curves in ROC curve of IFA and RT-PCR were 0.869 and 0.792, respectively. The inflammatory indexes were usually elevated in severe children compared with mild children. By binary logistic regression model analysis, neutrophil-to-lymphocyte ratio, D-dimer/fibrinogen and prognosis nutrition index were the risk factors and serum amyloid A/C reactive protein ratio was the protective factor for severe children with influenza A, and the OR values of the above factors were 1.760, 7.076, 1.045, and 0.719, respectively, and P<0.01. By the Bayesian Interdiction Criterion, the optimal seasonal autoregressive moving average mixed model for influenza A epidemics was ARIMA (1, 1, 1) (2, 1, 2) 12 with the highest prediction accuracy of 98.63%. The seven strains of H3N2 all belonged to the same isoforms, with nucleotide similarity of the HA gene ranging from 99.5% to 99.9%, and the glycosylation site, receptor-binding site, and the conserved amino acid residue Glycosylation sites, receptor binding sites and conserved amino acid residues remained unchanged. HA sequence analysis showed that the prevalent strains in Nanyang had undergone mutation to different degree compared with the vaccine strains. Conclusion:Scientific and rational testing and characteristic inflammatory markers in the clinical laboratory are of great clinical value in the diagnosis of children with severe influenza A. At the same time, the epidemiological monitoring of influenza A variants should be strengthened.

Objective To evaluate the clinical efficacy and safety of Huoxue Jiedu Prescription in the treatment of polycythemia vera with heat toxicity and blood stasis syndrome.Methods Totally 155 patients of polycythemia vera with heat toxicity and blood stasis syndrome from 5 hospitals including Langfang Traditional Chinese Medicine Hospital from October 2022 to March 2024 were collected.Patients were divided into an observation group(79 cases)and control group(76 cases)using a random number table method.Both groups received conventional Western medicine treatment.The observation group was given Huoxue Jiedu Prescription,one dosage per day,taken orally twice a day;both groups received one treatment course of one month,and three treatment courses were observed.The efficacy of Western medicine and TCM syndromes was observed,and the total symptom assessment scale of myeloproliferative neoplasms(MPN-10)scores,hematological indicators,coagulation function before and after treatment were compared.The safety indicators of the two groups were monitored.Results The control group and observation group lost 2 and 4 cases,respectively.The total effective rate of Western medicine in the observation group was 90.67%(68/75),while the control group was 67.57%(50/74),with statistical significance(P<0.01).The total effective rate of TCM syndromes in the observation group was 94.67%(71/75),while in the control group was 71.62%(53/74),with statistical significance(P<0.01).Compared with before treatment,the total score of MPN-10 in both groups significantly decreased(P<0.05);after treatment,the total score of MPN-10 in the observation group was lower than that in the control group(P<0.05).Compared with before treatment,both groups showed significant reductions in hemoglobin,white blood cell count,hematocrit and platelet count after treatment(P<0.05);after treatment,the above hematological indicators in the observation group were better than those in the control group(P<0.05).Compared with before treatment,the levels of D-dimer and fibrinogen in both groups significantly decreased after treatment,and the activated partial thromboplastin time and prothrombin time were significantly shortened(P<0.05);after treatment,the observation group showed better improvement in the coagulation function indicators compared to the control group(P<0.05).There were no significant adverse reactions in the two groups.Conclusion Huoxue Jiedu Prescription can improve clinical efficacy of polycythemia vera with heat toxicity and blood stasis syndrome,improve hematological indexes,reduce coagulation indexes,and has good safety.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.