Objective To investigate and compare the epidemiological characteristics of common respiratory viruses among influenza-like illness(ILI)and severe acute respiratory infection(SARI)cases in Huzhou,Zhejiang Province before and after the COVID-19 pandemic,so as to provide a basis for formulating and adjusting the prevention and control strategies for viral respiratory infectious diseases.Methods ILI and SARI cases at two influenza surveillance sentinel hospitals in Huzhou and had throat swab samples collected during Nov 2017 to Feb 2020(pre-COVID-19 pandemic period)and Dec 2022 to Apr 2024(post-COVID-19 mitigation phase)were selected as the participants.Seven common viral respiratory pathogens were tested,including influenza A virus(H1N1 and H3N2 subtypes),influenza B virus(Victoria lineage,FluB),respiratory syncytial virus(RSV),rhinovirus(HRV),adenovirus(ADV),and severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).The positive rates of respiratory pathogens before and after the COVID-19 pandemic were compared across different age groups and different time.Results A total of 7 948 ILI samples and 2 294 SARI samples were included.The overall positive rate of ILI samples increased from 33.6%to 47.1%,primarily due to the increase in influenza and COVID-19 infections;the overall positive rate of SARI samples decreased from 31.4%to 24.8%,mainly due to the reduction in HRV and ADV infections.During the post-COVID-19 mitigation phase,SARS-CoV-2(22.1%),H3N2(12.7%),and FluB(6.0%)were the primary pathogens in ILI samples,while RSV(7.1%),H3N2(5.3%),and HRV(4.5%)dominated in SARI samples.During the post-COVID-19 mitigation phase,the influenza virus circulation period was shortened.Before the COVID-19 pandemic,RSV was mainly detected in autumn and winter,while during the post-COVID-19 mitigation phase,out-of-season RSV epidemics were observed in spring and summer.Co-infection rate in ILI cases increased significantly in the post-COVID-19 mitigation phase,predominantly consisting of co-infections of COVID-19 and influenza A virus,while co-infection rate in SARI cases showed a decline.Conclusion We found important epidemiological changes in respiratory viruses in Huzhou during the post-COVID-19 mitigation phase compared to pre-COVID-19 period,including increased positive rates of influenza and COVID-19,and disruptions to the seasonal patterns of influenza and RSV.The prevention and control strategies should be adjusted in a timely manner based on the monitoring data.

AIM:To determine the concentration of ARV-471(a representative PROTAC drug)in mice plasma by establishing an HPLC-MS/MS method and to apply this method in pharmacokinetic studies in mice.METHODS:Verapamil was taken as the inter-nal standard,the mice plasma samples were extract-ed by methanol.After centrifugation,the superna-tant was analyzed by liquid chromatography-mass spectroscopy(LC-MS/MS).Chromatographic col-umn:ACQUITY UPLC HSS T3(1.8 μm,2.1 mm × 50 mm);The mobile phase consists of acetonitrile(containing 0.1％formic acid)and 2 mmol/L ammoni-um formate aqueous solution(containing 0.1％for-mic acid)for gradient elution;flow-rate of 0.6 mL/min;injection volume:2 μL.The electrospray ioniza-tion(ESI)is employed,operating in positive ion scan-ning mode with multiple reaction monitoring(MRM)detection.The specificity,standard curve and quanti-fication limit,precision and accuracy,recovery rate and matrix effect,stability and dilution reliability of this method were examined.Furthermore,the plas-ma concentration and pharmacokinetic parameters of ARV-471 in mice after intravenous injection of 5 mg/kg and oral gavage of 30 mg/kg were deter-mined and calculated.RESULTS:The results dem-onstrate that ARV-471 exhibits a good linear rela-tionship within the concentration range of 2.0 to 2 000.0 ng/mL.The intra-and inter-accuracy were between 80.0％and 120.0％,with the intra-and in-ter-precision less than 15％.The results of method-ological study of specificity,matrix effect,stability conformed to the requirements of the guideline.Pharmacokinetic parameters reveal that after oral administration of 30 mg/kg ARV-471 to male and fe-male mice,Cmax were(2 947.19±454.77)and(2 682.02±342.23)ng·mL-1;AUC0-twere(23 357.37±3 488.00)and(20 161.23±1 871.32)ng·h·mL-1;T1/2were(3.11±0.18)and(2.93±0.62)h.Tmax were(1.83±0.41)and(2.00±0.00)h for male and fe-male mice,respectively.After intravenous adminis-tration of 5 mg/kg ARV-471 to male and female mice,the AUC0-t values were found to be(18 219.07±2 059.41)and(17 238.01±2 380.55)ng·h·mL-1;T1/2 values were(2.76±0.23)and(2.73±0.20)h;The absolute bio-availability of ARV-471 were deter-mined to be(19.49±1.81)％and(21.37±3.19)％for male and female mice,respectively.CONCLU-SION:This study establishes a rapid and effective method for the pharmacokinetic research of ARV-471,laying the foundation for the pharmacokinetic studies of PROTAC drugs.

Based on the results of the National Drug Sampling and Inspection Programme,we summarized the history,the standard collection,the production enterprises and the dosage form specifications,the quality standard study,the pharmacological and pharmacodynamic study,and the clinical application study of Wuwei Qingzhuo preparation of Mongolian medicine and Shiliu Jianwei preparation of Zang medicine,to provide the basis for improved quality standards for both preparations.The development of these two preparations was searched and analyzed through literature.The available information shows that there is very little research on the two preparations and insufficient pharmacological experimental and clinical experimental data.The two preparations are basically the same in prescription and efficacy.However,the quality standards are very different,which are not conducive to the quality control of the two and their related dosage forms.And it is suggested that the Chinese Pharmacopoeia should take the situation of this category into comprehensive consideration,and unify the quality standards of the two preparations.

Objective To investigate and compare the epidemiological characteristics of common respiratory viruses among influenza-like illness(ILI)and severe acute respiratory infection(SARI)cases in Huzhou,Zhejiang Province before and after the COVID-19 pandemic,so as to provide a basis for formulating and adjusting the prevention and control strategies for viral respiratory infectious diseases.Methods ILI and SARI cases at two influenza surveillance sentinel hospitals in Huzhou and had throat swab samples collected during Nov 2017 to Feb 2020(pre-COVID-19 pandemic period)and Dec 2022 to Apr 2024(post-COVID-19 mitigation phase)were selected as the participants.Seven common viral respiratory pathogens were tested,including influenza A virus(H1N1 and H3N2 subtypes),influenza B virus(Victoria lineage,FluB),respiratory syncytial virus(RSV),rhinovirus(HRV),adenovirus(ADV),and severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).The positive rates of respiratory pathogens before and after the COVID-19 pandemic were compared across different age groups and different time.Results A total of 7 948 ILI samples and 2 294 SARI samples were included.The overall positive rate of ILI samples increased from 33.6%to 47.1%,primarily due to the increase in influenza and COVID-19 infections;the overall positive rate of SARI samples decreased from 31.4%to 24.8%,mainly due to the reduction in HRV and ADV infections.During the post-COVID-19 mitigation phase,SARS-CoV-2(22.1%),H3N2(12.7%),and FluB(6.0%)were the primary pathogens in ILI samples,while RSV(7.1%),H3N2(5.3%),and HRV(4.5%)dominated in SARI samples.During the post-COVID-19 mitigation phase,the influenza virus circulation period was shortened.Before the COVID-19 pandemic,RSV was mainly detected in autumn and winter,while during the post-COVID-19 mitigation phase,out-of-season RSV epidemics were observed in spring and summer.Co-infection rate in ILI cases increased significantly in the post-COVID-19 mitigation phase,predominantly consisting of co-infections of COVID-19 and influenza A virus,while co-infection rate in SARI cases showed a decline.Conclusion We found important epidemiological changes in respiratory viruses in Huzhou during the post-COVID-19 mitigation phase compared to pre-COVID-19 period,including increased positive rates of influenza and COVID-19,and disruptions to the seasonal patterns of influenza and RSV.The prevention and control strategies should be adjusted in a timely manner based on the monitoring data.

AIM:To observe the effect of continuous light on the structure and differential metabolites of gut microbiota in mice.METHODS:The mice were randomly divided into normal light(light/dark,LD)group and 24-hour continuous light(light/light,LL)group.The body weight,fasting blood glucose,serum free fatty acids,serum triacylglycerol and serum total cholesterol levels of each group of mice were measured after 10 weeks.Fresh feces were collected,and 16S rRNA sequencing technology was used to study the effect of continuous light on the diversity,structure,and species composition of gut microbiota in mice.Additionally,liquid chromatography-mass spectrometry(LC-MS)analysis was per-formed to observe the effect of continuous light on the metabolites in mice.RESULTS:Compared with the LD group,the body weight,fasting blood glucose and lipid levels of the LL group were increased(P＜0.05).At the phylum level,the proportion of Firmicutes in the LL group increased,while the proportion of Bacteroidetes decreased.At the class level,the abundance of norank_f_Muribaculaceae and Prevotellaceae_UCG-001 in the LL group decreased significantly,while the abundance of Lactobacillus,Turicibacter and Odoribacter increased significantly.Non-targeted metabolomics analysis iden-tified 65 and 73 differential metabolites under positive and negative modes,involving six major metabolic pathways,in-cluding ABC transporters,purine metabolism,pyrimidine metabolism,secondary bile acid biosynthesis,protein digestion and absorption,and choline metabolism in cancer.CONCLUSION:The structure and metabolites of gut microbiota in mice exposed to continuous light are relatively specific,and inosine may be a key biomarker and potential therapeutic tar-get for biological clock disorders.

Objective To examine the quality of Zukamu preparations through the national drug sampling and testing,and further understand their current quality status and existing problems.This work is benefit for improving the quality standard of Zukamu preparations and providing technical support for the drug regulatory authorities.Methods Samples of Zukamu preparations were collected from a total of 29 provinces in China,and were tested for description,identification,other requirements(weight variation,particle size,determination of water,disprsion,and microbial limit items),and assay in accordance with the national pharmaceutical standards.The test data were analyzed to evaluate the quality status of the Zukamu preparations,and exploratory research was carried out to address the problems found in the test.Results A total of 97 batches of Zukamu preparations were sampled,and the passing rate was 100.0%according to the current quality standard.Exploratory study,revealed that Zukamu preparation were subject to 4 testing standards,with uneven test items,missing items,poor operability,and lack of exclusivity in some items.The test based on the existing standards can't comprehensively evaluate the quality of the preparation.Conclusions Based on the national drug sampling and testing,combined with exploratory research on drug safety,authenticity and effectiveness,it is recommended to unify the quality standards of Zukamu preparations by combining with the work of standard improving,revising the identification method of thin-layer chromatography,increasing the content determination,and establishing the quick test method,thereby effectively evaluating and controling the quality of the samples of Zukamu preparations.

Aim To investigate the anti-Zika virus(ZIKV)mechanism of diterpenoid compound 9 from Euphorbia helioscopia in vitro.Methods The cytotox-icity of compound 9 was evaluated using the CCK-8 as-say.A ZIKV-infected Vero cell model was established,and the antiviral activity was assessed through RT-qPCR,plaque assay,Western blot,and immunofluores-cence.Furthermore,the mechanism of action was elu-cidated using multi-cell line validation,nanoparticle tracking analysis,cellular thermal shift assay,and mo-lecular docking.Results In Vero cells,compound 9 exhibited an EC50 of(3.95±0.15)μmol·L-1 and a CC50 of(272.12±8.56)μmol·L-1,demonstrating significantly higher antiviral efficacy than the positive control drug ribavirin(RBV).Its virus inactivation effect was time-dependent and could significantly re-duce viral load and plaque formation.Studies revealed that compound 9 altered the physicochemical properties of ZIKV particles,including reducing surface charge and increasing particle size distribution.Additionally,it significantly enhanced the thermal stability of the prM protein.Molecular docking analysis indicated that compound 9 formed a high-affinity interaction with the prM protein(binding energy:-38.52 kJ·mol-1)and stabilized its structure through hydrophobic interac-tions.Conclusion Compound 9 exerts in vitro anti-ZIKV activity by directly inactivating the virus,disrup-ting viral particle integrity,and targeting the prM pro-tein.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Objective:To evaluate the clinical efficacy of the operation treated of unilateral unstable sacral fracture with S 1 dysplasia by bi-perforative screws of the middle and posterior pelvic columns. Methods:A retrospective analysis was conducted on 18 patients with proximal S 1 dysplasia and unilateral unstable sacral fractures treated at Tianjin Hospital, from January 2018 to January 2023. The cohort included 10 males and 8 females, with an average age of 46.3±1.2 years (range, 18-56 years). The causes of injury were traffic accidents in 12 cases and falls in 6 cases. All patients had combined anterior pelvic ring injuries, including 14 cases of simple fractures and 4 cases of fractures combined with pubic symphysis injuries. Preoperative neuro-magnetic resonance imaging (MRI) confirmed that the lumbosacral nerves were not compressed by fracture fragments or displaced bone ends. According to the Dennis classification, there were 8 cases of type I and 10 cases of type II sacral fractures. Abnormalities in S 1 development included 9 cases of steep slopes, 6 cases of anterior rim depression, and 3 cases of both deformities simultaneously. There were 2 cases of nerve injury, both of which were Gibbons grade II. The average time from injury to surgery was 5.4±1.7 days (range, 4-14 days). All patients underwent combined anterior and posterior pelvic fixation in a single stage, with sacral fractures fixed using bi-perforative screws of posterior pelvic ring. The following parameters were recorded: screw placement time, intraoperative blood loss, fluoroscopy time, fracture healing time, accuracy of internal fixation placement, postoperative infection rate, and iatrogenic injury incidence. The Mears scoring system was used to evaluate the satisfaction rate of sacral fracture reduction, the Gibbons classification was used to assess neurological recovery, and the Majeed score was used to evaluate pelvic function. Results:The average screw placement time was 38.7±3.5 min for S 1 and 16.5±1.3 min for the posterior column. The average blood loss during screw placement was 30.53±1.61 ml, and the average fluoroscopy time was 11.3±3.2 s. No vascular or nerve injuries occurred in any case after the operation. All sacral fractures healed, with an average healing time of 7.6±2.2 months (range, 3-12 months). No cases of fracture re-displacement or internal fixation failure were observed. The Mears evaluation results showed anatomical reduction in 12 cases, satisfactory reduction in 4 cases, and unsatisfactory reduction in 2 cases. All internal fixations were accurately placed. All 18 patients were followed up with an average of 18.2±2.5 months (range, 12-36 months). At the last follow-up, the average Majeed score was 87.4±2.9, with 11 cases rated as excellent, 4 as good, and 3 as fair. The two patients with Gibbons grade II nerve injuries improved to grade I postoperatively. Conclusion:Bi-perforative screws fixation for the middle and posterior pelvic columns offers several advantages, including straightforward operation, precise minimally invasive placement, safety and efficacy, robust fixation, and low complication rates, resulting in satisfactory clinical outcomes.

AIM:To observe the effect of continuous light on the structure and differential metabolites of gut microbiota in mice.METHODS:The mice were randomly divided into normal light(light/dark,LD)group and 24-hour continuous light(light/light,LL)group.The body weight,fasting blood glucose,serum free fatty acids,serum triacylglycerol and serum total cholesterol levels of each group of mice were measured after 10 weeks.Fresh feces were collected,and 16S rRNA sequencing technology was used to study the effect of continuous light on the diversity,structure,and species composition of gut microbiota in mice.Additionally,liquid chromatography-mass spectrometry(LC-MS)analysis was per-formed to observe the effect of continuous light on the metabolites in mice.RESULTS:Compared with the LD group,the body weight,fasting blood glucose and lipid levels of the LL group were increased(P＜0.05).At the phylum level,the proportion of Firmicutes in the LL group increased,while the proportion of Bacteroidetes decreased.At the class level,the abundance of norank_f_Muribaculaceae and Prevotellaceae_UCG-001 in the LL group decreased significantly,while the abundance of Lactobacillus,Turicibacter and Odoribacter increased significantly.Non-targeted metabolomics analysis iden-tified 65 and 73 differential metabolites under positive and negative modes,involving six major metabolic pathways,in-cluding ABC transporters,purine metabolism,pyrimidine metabolism,secondary bile acid biosynthesis,protein digestion and absorption,and choline metabolism in cancer.CONCLUSION:The structure and metabolites of gut microbiota in mice exposed to continuous light are relatively specific,and inosine may be a key biomarker and potential therapeutic tar-get for biological clock disorders.