ObjectiveTo analyze the epidemiological characteristics and trends of hand-foot-mouth disease (HFMD) in Hangzhou, so as to provide an evidence for developing effective prevention and control measures and evaluating the control effects. MethodsThe incidence data of HFMD in Hangzhou were collected from the Infectious Disease Reporting Information Management System of China Information System for Disease Control and Prevention. Descriptive epidemiology was applied to analyze the temporal, spatial and demographic distribution characteristics and etiology monitoring results of HFMD cases in Hangzhou from 2010 to 2023. Joinpoint regression model was used to analyze the trends of incidence rate of HFMD. Furthermore, circular distribution method was utilized to calculate the incidence peak of HFMD. ResultsFrom 2010 to 2023, the average annual reported incidence rate of HFMD in Hangzhou was 138.85/100 000, the proportion of severe cases was 0.04%, the mortality rate was 0.01/100 000, and the case fatality rate was 5.30/100 000. Both the total incidence rate and the incidence rate by sex showed an increasing trend. The annual reported incidence rate in males (158.72/100 000) was higher than that in females (117.61/100 000). The reported incidence rate showed a significant seasonal characteristic, with summer being the peak of epidemic. The results of surveillance samples suggested that the prevalence of HFMD in Hangzhou is characterized by the co-existence of multiple pathogens, with EV-A71 and CV-A16 being the dominant pathogens in the previous years and CV-A6 being the dominant pathogen since 2018. The proportion of EV-A71 in severe cases (77.19%) was higher than that in ordinary cases (15.37%), in addition, its proportion in ordinary cases, severe cases, and fatal cases all showed a decreasing trend. ConclusionThe incidence rate of HFMD in Hangzhou is still high, so it’s still necessary to continue to strengthen the prevention and control measures for key populations. In recent years, CV-A6 has been the main prevalent pathogen in Hangzhou. Further efforts in pathogen detection and analysis should be enhanced in the future.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Taxifolin (TAX) is a natural compound known for its liver protection effect, but the mechanism remains unknown. Phosphorylated proteomics analyses discovered that the phosphorylation level of NDRG1 at T328 was a key event of TAX-improved liver fibrosis. We established models with NDRG1 knockout (KO) in vivo and in vitro, demonstrating that NDRG1 KO attenuated the development of hepatocyte injury, and combining NDRG1 KO and TAX administration did not result in a reduction in protection against liver injury. Cellular thermal shift assay and surface plasma resonance analysis showed that TAX directly binds to NDRG1 rather than its upstream kinase, subsequently demonstrating that TAX regulated phosphorylation of NDRG1 at T328 through binding to its C289 site. NDRG1 T328A (phosphorylated mutation) and T328E (mimic phosphorylation) in vivo and in vitro confirmed that pNDRG1_T328 exacerbates hepatocyte injury along with DNA damage, inflammatory response, and apoptosis, thereby contributing to hepatic stellate cells (HSCs) activation. In contrast, TAX can inhibit the above pathological abnormalities and block hepatocyte injury-triggered HSCs activation and fibrosis. Overall, TAX is a potent liver protection drug primarily targeting NDRG1 and inhibiting pNDRG1_T328 in hepatocytes.

The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Descriptive epidemiological methods were used to analyze the epidemiological characteristics of the local cluster of COVID-19 in the logistic park of Yuhang District in Hangzhou in March 2022. The cluster epidemic was detected by a case who actively visited the fever clinic. The epidemic lasted for 8 days, and a total of 58 cases (53 workers, 2 students, 1 farmer, 1 teacher and 1 unemployed) were found, including 40 males and 18 females. The age was (33.29±12.22) years. There cases were mainly in Yuhang District (48 cases, 82.77%) and Shangcheng District (7 cases, 12.07%) of Hangzhou. The real-time regeneration number peaked at 2.31 on March 10 th and decreased to 0.37 on March 15 th. The sequencing result of the indicated case was 100% homologous with the sequence uploaded from South Korea on March 4 th, 2022.

Objective To investigate the clinical effect of anterior cervical discectomy and fusion(ACDF)in the treatment of cervical spondylosis of vertebral artery type(CSA).Methods The clinical data of 42 patients with CSA from January 2020 to January 2022 were retrospectively analyzed.There were 25 males and 17 females,aged from 30 to 74 years old with an average of(53.9±11.0)years old.There were 18 cases with single-segment lesions,17 cases with two-segment lesions,and 7 cases with three-segment lesions.The American Academy of Otolaryngology-Head and Neck Surgery's Hearing and Balance Committee score(CHE),the Neck Disability Index(NDI)and the cervical curvature Cobb angle were recorded before surgery and after surgery at 6 months.Results All 42 ACDF patients were followed up for 6 to 30 months with an average of(14.0±5.2)months.The operative time ranged from 95 to 220 min with an average of(160.38±36.77)min,the intraoperative blood loss ranged from 30 to 85 ml with an average of(53.60±18.98)ml.Tow patients had mild postoperative dysphagia,which improved with symptomatic treatment such as nebulized inhalation.CHE score decreased from(4.05±0.96)preoperatively to(2.40±0.70)at 6 months postoperatively(t=12.97,P＜0.05).The number of improved vertigo at 6 months postoperatively was 38,with an im-provement rate of 90.5％.NDI score was reduced from(34.43±8.04)preoperatively to(20.76±3.91)at 6 months postopera-tively(t=1 1.83,P＜0.05).The cervical curvature Cobb angle improved from(8.04±6.70)° preoperatively to(12.42±5.23)° at 6 months postoperatively(t=-15.96,P＜0.05).Conclusion The ACDF procedure has outstanding clinical efficacy in treating CSA.The operation can rapidly relieve patients'episodic vertigo symptoms by relieving bony compression and reconstructing cervical curvature.However,it is necessary to strictly grasp the indications for surgery and clarify the causes of vertigo in pa-tients,and ACDF surgery is recommended for CSA patients for whom conservative treatment is ineffective.

Objective We aimed to compare the efficacy and prognosis of percutaneous coronary intervention(PCI)in complex and high-risk patients with coronary heart disease(CHD)treated with extracorporeal membrane oxygenation(ECMO)combined with intra-aortic balloon pump(IABP)assistance,and explore the application value of combined use of mechanical circulatory support(MCS)devices in complex PCI.Methods A total of patients who met the inclusion criteria and underwent selective PCI supported by MCS at the Department of Cardiology,the First Affiliated Hospital of the Air Force Medical University from January 2018 to December 2022 were continuously enrolled.According to the mechanical circulatory support method,the patients were divided into ECMO+IABP group and IABP group.Clinical characteristics,angiographic features,in-hospital outcomes,and complications were collected.The intra-hospital outcomes and major adverse cardiovascular events(MACE)at one month and one year after the procedure were observed.The differences and independent risk factors between the two groups in the above indicators were analyzed.Results A total of 218 patients undergoing elective PCI were included,of which 66 patients were in the ECMO+IABP group and 152 patients were in the IABP group.The baseline characteristics of the two groups of patients were generally comparable,but the ECMO+IABP group had more complex lesion characteristics.The proportion of patients with atrial fibrillation(6.1％vs.0.7％,P=0.030),left main disease(43.9％vs.27.0％,P=0.018),triple vessel disease(90.9％vs.75.5％,P=0.009),and RCA chronic total occlusion disease(60.6％vs.35.5％,P＜0.001)was higher in the ECMO+IABP group compared to the IABP group.The proportion of patients with previous PCI history was higher in the IABP group(32.9％vs.16.7％,P=0.014).There was no statistically significant difference in the incidence of in-hospital complications between the two groups(P=0.176),but the incidence of hypotension after PCI was higher in the ECMO+IABP group(19.7％vs.9.2％,P=0.031).The rates of 1-month MACE(4.5％vs.2.6％,P=0.435)and 1-year MACE(7.6％vs.7.9％,P=0.936)were comparable between the two groups.Multivariate analysis showed that in-hospital cardiac arrest(OR 7.17,95％CI 1.27-40.38,P=0.025)and after procedure hypotension(OR 3.60,95％CI 1.10-11.83,P=0.035)were independent risk factors for the occurrence of 1-year MACE.Conclusions Combination use of ECMO+IABP support can provide complex and high-risk coronary heart disease patients with an opportunity to achieve coronary artery revascularization through PCI,and achieve satisfactory long-term prognosis.

Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying mechanisms.In vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-β(TGF-β).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated his-topathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw form.Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)pathway.Of note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and caspase9.small interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3.In conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mecha-nism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.