Objective To understand the antibody levels of diphtheria and tetanus among healthy population in Shanghai Pudong New Area, and to provide a scientific basis for improving the vaccine immunization strategy. Methods Random sampling was used to select healthy people of all ages in 16 communities in Shanghai Pudong New Area from 2018 to 2024, and serum samples were collected and tested for serum anti-diphtheria and tetanus toxin IgG antibodies by enzyme-linked immunosorbent assay (ELISA) method to analyze the antibody positivity rate (≥0.1 IU/ml) and the geometric mean concentration (GMC) of antibodies. Results A total of 3 312 serum samples were included, with a male-to-female ratio of 0.76:1, and 53.77% were local residents. The seropositivity rates and geometric mean concentrations (GMC) of both diphtheria and tetanus antibodies generally declined with increasing age, but exhibited a transient rebound in the 7y-. A total of 1 175 individuals (35.48%) were seropositive for diphtheria, with a GMC of 0.054 IU/mL. For tetanus, 988 individuals (29.83%) were seropositive, with a GMC of 0.033 IU/mL. Significant differences in seropositivity rates (χ²_diphtheria=950.005,χ²_tetanus=1 324.393) and GMC (H_diphtheria=1027.160,H_tetanus=1 142.007) were observed among different age groups (P<0.001). Significant differences in seropositivity rates (χ²_diphtheria=950.005,χ²_tetanus=1324.393) and GMC (H_diphtheria=1027.160,H_tetanus=1142.007) were also found across different years (P<0.001). Conclusion The prevalence of diphtheria and tetanus antibodies in the healthy population of Pudong New Area is relatively low, particularly among adults over 20 years of age with inadequate immunization. This underscores the need to reinforce the National Immunization Program (NIP) vaccine specifications for children under 6 years of age and implement an immunization strategy for adolescents or adults against diphtheria and tetanus.

ObjectiveTo analyze the epidemiological and etiological characteristics of a cluster of human metapneumovirus (HMPV) infection in a kindergarten in Gongshu District of Hangzhou City in May 2024, and to provide reference for the prevention and control of similar outbreaks. MethodsAn on-site investigation was conducted using an epidemiological case investigation form. Throat swab specimens collected from cases were screened for 13 respiratory pathogens using real-time fluorescent polymerase chain reaction (PCR). For HMPV nucleic acid positive specimens, the F gene of HMPV was used as the target gene for amplification and sequencing. The sequencing results were then compared with sequences in GenBank database to determine the virus subtypes and perform phylogenetic analyses. ResultsThe outbreak occurred in a kindergarter junior class with a total of 28 preschoolers and 3 teachers and childcare workers. A total of 11 cases (10 preschoolers and 1 teacher) were identified, including 8 male cases and 3 female cases. Clinical manifestations included fever in all 11 cases (100.00%), cough in 8 cases (72.72%), catarrhal symptoms in 4 cases (36.36%), and headache in 3 cases (27.27%). All symptoms were mild, and no severe cases were observed. A total of 11 throat swab samples were collected. Real-time fluorescent PCR test results showed that 3 samples were positive for HMPV nucleic acid, 2 samples were positive for both HMPV and Streptococcus pneumoniae, and 1 sample was positive for both HMPV and rhinovirus. The sequences of the 6 HMPV nucleic acid positive specimens were amplified and analyzed using specific primers, and all were determined to be HMPV subtype A2b. The F gene fragment sequence showed the highest similarity to PV081665.1/Brazil/2024 (99.65%), and also exhibited high similarity to PP683455.1/Indonesia/2021 (99.48%), PV016275.1/Beijing/2024 (99.31%), and PV052230.1/USA/2024 (99.13%). ConclusionThis cluster of acute respiratory tract infection was caused by HMPV subtype A2b, with co-infection of rhinovirus and Streptococcus pneumoniae. The F gene fragment sequences of the HMPV in this outbreak were highly homologous to those of the A2b strains isolated from Brazil, Beijing, Indonesia, and the the United States.

Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca²⁺, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Objective:To investigate the clinical efficacy of laparoscopic hiatal hernia repair with tunneled esophagogastric fundoplication and diaphragmatic dome suspension-fixation (HHR-TEF-DDSF) in the treatment of gastroesophageal reflux disease.Methods:The retrospective and descriptive study was conducted. The clinical data of 32 patients with gastroesophageal reflux disease who were admitted to Yifu Hospital Affiliated to Nanjing Medical University from October 2024 to June 2025 were collected. There were 20 males and 12 females, aged (68±7)years. All patients underwent laparoscopic HHR-TEF-DDSF. Observation indicators: (1) surgical and intraoperative conditions; (2) postoperative conditions; (3) follow-up. Measurement data with normal distribution were expre-ssed as Mean± SD, while measurement data with skewed distribution were expressed as M( Q1, Q3) or M(range). Count data were expressed as absolute numbers or percentages. Results:(1) Surgical and intraoperative conditions. All 32 patients successfully underwent laparoscopic HHR-TEF-DDSF. The operation time was (75±10)minutes, and volume of intraoperative blood loss was 50(50,100)mL. Among the 32 patients, there was no conversion to open surgery, no blood transfusion, no intra-operative complications such as unexpected massive hemorrhage or adjacent organ injury, no intra-operative adverse event or death. (2) Postoperative conditions. For the 32 patients, the time to post-operative first flatus was 1(1,2)days, the time to postoperative first defecation was 1(1,3)days, the time to postoperative first intake of liquid food was 1(1,3)days, the duration of postoperative drainage tube indwelling was 3(3,6)days, the postoperative hospital stay was 6(5,14)days, and the time to relief of postoperative dysphagia was 5(5,8)days. No obvious hiccup was observed in any patient in the short term after surgery. (3) Follow-up. All 32 patients were followed up for 7.5(range, 3.0-11.0)months. Among the 32 patients, 26 cases achieved subjective relief of overall postoperative digestive tract symptoms, and 32 cases achieved subjective relief of overall postoperative respiratory tract symptoms. The proton pump inhibitor (PPI) withdrawal rate was 84.4%(27/32), and the treatment satisfaction rate was 87.5%(28/32). The incidences of postoperative complications inclu-ding abdominal distension, dysphagia, diarrhea, and increased flatus were 21.9%(7/32), 18.8%(6/32), 6.3%(2/32), and 3.1%(1/32), respectively. Dysphagia was significantly relieved in all affected patients within 2 months after surgery, and no patient had persistent dysphagia by the end of the follow-up period. There was no death, symptom recurrence, or reoperation.Conclusion:HHR-TEF-DDSF is safe and feasible in the treatment of gastroesophageal reflux disease, with favorable short-term efficacy.

The aim of this paper was to investigate the serotypes,virulence factors and drug resist-ance of clinical isolates of Pasteurella rnultocida of porcine origin in recent years.Morphological screening and polymerase chain reaction(PCR)were used to isolate and identify 119 isolates from nasal swabs and lung tissue samples sent from swine farms in Zhejiang Province from 2010 to 2024.The isolates of Pasteurella multocida were subjected to capsular polysaccharide serotyping,lipopolysaccharide serotyping,virulence factor detection and drug resistance analysis by PCR and Kirby-Bauer disc agar diffusion method(K-B).The results showed that there were 64 strains(53.7％)of A-type,54 strains(45.3％)of D-type and 1 strain(0.9％)of F-type among the capsu-lar polysaccharide serotypes,and 10 strains(8.4％)of L1-type,20 strains(16.8％)of L3-type,86 strains(72.2％)of L6-type,and 3 strains(2.6％)of undetermined type among the lipopolysaccha-ride serotypes.The amplification results of 10 virulence genes showed that the detection rate of virulence genes hgbA,higbB and fimA was over 86.0％,the detection rate of toxA was 8.4％,while the virulence gene tbpA was not detected.There were also differences in the distribution vir-ulence genes in different capsular polysaccharide serotypes.Virulence factor pfhA was detected in type A and F but not in type D.The detection rate of adhesin gene tadD in serotype A(92.2％)was significantly higher than that of type D(9.3％),and,on the contrary,the detection rate of ad-hesin gene hsf-l in serotype D(90.7％)was significantly higher than that of type A(20.3％).Drug resistance analysis revealed that Pasteurella multocida showed high susceptibility to antimi-crobial drugs such as amoxicillin,ampicillin,cephalosporins,doxycycline,fosfenicol and ciprofloxa-cin,and showed strong resistance to antimicrobial drugs such as lincomycin,cotrimoxazole,genta-micin and amikacin,and there were 54 multi-drug resistant strains(78.3％).In summary,capsular polysaccharide serotypes were dominated by type A and D,lipopolysaccharide serotypes were dom-inated by L6,the distribution of some virulence genes varied greatly among different serotypes,and the proportion of multi-resistant strains was high,which provide reference for the prevention and control of this disease.

Aim To investigate the protective effect of liraglutide(LIRA)on acetaminophen(APAP)-in-duced hepatotoxicity at the in vivo level and to reveal the underlying mechanism.Methods Forty SPF grade male C57BL/6J mice were randomly divided into the Control,LIRA(200 μg·kg-1),APAP(500 mg·kg-1),LIRA+APAP,LIRA+APAP+3-methylade-nine(3-MA,30 mg·kg-1)groups,with eight mice in each group.The mice were administered for three con-secutive days,and the materials were taken after 24 h.The general condition and body weight of mice in each group were recorded,and liver morphology was ob-served.Serum ALT and AST levels,as well as SOD ac-tivity,MDA,and GSH content in liver homogenates,were measured using biochemical assay kits.The levels of inflammatory cytokines IL-6,TNF-α,and IL-1β in serum were detected by ELISA.Liver pathological changes were assessed by HE staining,while mitochon-drial and autophagosome structures in liver tissues were observed using transmission electron microscopy.The number of PCNA-positive cells in liver tissues was e-valuated using immunohistochemical staining.The pro-tein expression levels of LC3Ⅱ,p62,Bax,Bcl-2,PC-NA,and CyclinD1 in liver tissues were determined by Western blot.Results LIRA pretreatment can im-prove the general condition of mice with acetamino-phen-induced liver injury(AILI),reduce serum ALT and AST levels,and effectively ameliorate the appear-ance and morphology of the liver as well as the patho-logical damage to liver tissue.Simultaneously,the lev-els of inflammatory cytokines IL-6,TNF-α,and IL-1βare significantly decreased;SOD activity and GSH con-tent are significantly increased,while MDA content is significantly reduced.Transmission electron microsco-py observations reveal the presence of numerous auto-phagosomes in the cytoplasm of liver tissue.Immuno-histochemical staining results indicate a significant in-crease in the number of PCNA-positive cells.Further-more,the expression of LC3Ⅱ,Bcl-2,PCNA,and Cy-clinD1 proteins in liver tissue is significantly upregulat-ed,while the expression of p62 and Bax proteins is significantly downregulated.However,after interven-tion with the autophagy inhibitor 3-MA,the aforemen-tioned protective effects of LIRA are significantly.Conclusions LIRA pretreatment can significantly im-prove liver injury in AILI mice.Its protective mecha-nism may be related to enhancing autophagy in hepato-cytes,thereby reducing oxidative stress,inflammatory response and apoptosis in liver of AILI mice.

Objective To observe the value of 68Ga-DOTA-NOC PET/CT for diagnosing pheochromocytoma(PCC)and paraganglioma(PGL).Methods Thirty-eight patients with suspected or confirmed PCC/PGL who underwent 68 Ga-DOTA-NOC PET/CT were retrospectively enrolled,among them 20 cases underwent 131I-metaiodobenzylguanidine(MIBG)SPECT/CT during the same period.The value of 68Ga-DOTA-NOC PET/CT for diagnosing PCC/PGL at individual and lesion levels were analyzed and compared to the results of 131I-MIBG SPECT/CT.Results Among 38 cases,there were 20 cases of PCC,14 cases of PGL,1 case of adrenocortical carcinoma and 3 cases of benign adrenal hyperplasia.The sensitivity,specificity,positive predictive value,negative predictive value and accuracy of 68 Ga-DOTA-NOC PET/CT for diagnosing PCC/PGL in all 38 cases was 87.88％(29/33),60.00％(3/5),93.55％(29/31),42.86％(3/7)and 84.21％(32/38),respectively.Totally 188 lesions were detected in 34 cases,with detection rate of 89.95％(188/209).For 20 patients who underwent both 2 kinds examinations,the detection rate of bone,lymph node,liver,lung metastases and the overall lesions of 68Ga-DOTA-NOC PET/CT were all higher than those of 131I-MIBG SPECT/CT(all P＜0.05).No significant difference of diagnostic accuracy of PCC/PGL was found between 68 Ga-DOTA-NOC PET/CT and 131I-MIBG SPECT/CT(P＞0.05).Conclusion The value of 68 Ga-DOTA-NOC PET/CT for diagnosing PCC/PGL was comparable to that of 131I-MIBG SPECT/CT,but the former showed higher detection rate of metastases,hence being helpful to staging and risk stratification of PCC/PGL.

Objective:To analyze the learning curve of TiRobot-assisted lumbar pedicle screw fixation (LPSF) by cumulative sum (CUSUM) test method.Methods:The clinical data of 50 patients who underwent TiRobot-assisted LPSF from January 2020 to December 2022 in Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. CUSUM analysis and learning curve fitting were performed with robot usage time as the main indicator with the time for each step refined (robot registration time, path planning time and guide wire placement time), to select the best learning curve fitting model with the R2 value closest to 1. Using the turning point of the learning curve as the boundary, the learning curve was divided into two stages as learning stage and maturity stage, and then the observation indexes were compared between the two stages. Results:All 50 patients successfully completed the surgery without perioperative complications, with a total of 244 pedicle screws implanted. The total robot usage time and robot registration time showed a gradually decreasing trend with the increase of case number, and the learning curves were successfully fitted and reached their peaks at the seventeenth and thirteenth cases respectively. The entire learning process was divided into learning stage (17 cases) and maturity stage (33 cases) based on the turning point of the learning curve of total robot usage time. The path planning time and guide wire placement time did not show significant changes with the increase in the case number. The total robot usage time, robot registration time and the intraoperative blood loss in the learning stage were significantly higher than those in the maturity stage: (35.35 ± 1.58) min vs. (30.61 ± 0.43) min, (20.83 ± 1.56) min vs. (14.94 ± 0.29) min and 400 (150, 500) ml vs. 200 (110, 300) ml, the guide wire placement time of per screw was significantly lower than that in the maturity stage: 2.00 (1.83, 2.34) min/screw vs. 2.33 (2.13, 2.69) min/screw, and there were statistical differences ( P<0.05 or <0.01). There were no statistical difference in the path planning time, path planning time of per screw, guide wire placement time and the accuracy of screw placement between two stages ( P>0.05). Conclusions:TiRobot-assisted LPSF is a new technology with safety and effectiveness, and it has a relatively short learning curve. To achieve technological maturity, at least 17 surgeries are required with accumulated experience, and the robot registration is the main step of the learning process. After reaching maturity stage, the robot usage time is significantly shortened and intraoperative trauma is significantly reduced while the relatively high screw placement accuracy is ensured.

Objective:To evaluate the association between erectile dysfunction(ED)and myocardial infarction(MI)using two sample Mendelian randomization.Methods:A Mendelian randomization study was conducted using comprehensive data on ED and MI from extensive genome-wide association data.Using inverse variance weighted analysis for causal relationships,and correct for confounding factors using multivariate Mendelian randomization,the potential mediating effects were evaluated as well.Based on Gene-card data,the genes related to ED and MI were identified.Molecular docking was used to reveal spontaneously bound drug molecules.Results.Our study found that exposure to ED was a risk factor for MI(OR:1.001 0,95％CI:1.000 2-1.001 8,P=0.017 7),which also held true in the validation dataset(OR:1.028 5,95％CI:1.005 0-1.052 6,P=0.017 2).No statistically significant heterogeneity or horizontal pleiotropy was found.The results of reverse Mendelian randomization analysis showed any reverse causal re-lationship between ED and MI.In multivariate Mendelian randomization analysis,after excluding confounding factors(excluding tri-glycerides and high-density lipoprotein),the P-value remained less than 0.05,and the OR ranged from 1.000 1 to 1.000 7,indica-ting that ED was still a risk factor for MI.In the mediation analysis,it was found that the current mediation ratio of smoking to MI was 13.06％.In summary-data-based mendelian randomization analysis,it was found that the gene PTPN11 was a common target gene for MI and ED(OR=0.990,P＜0.001).Subsequent molecular docking with sildenafil,clopidogrel,and dapoxetine could spontaneous-ly bind to the PTPN11 gene receptor.Conclusion:There is a causal relationship between ED and MI,with smoking as a potential mediating factor,and the gene PTPN11 being a co-target gene.