Tetanus is a potentially life-threatening neurological condition, and the prevention and treatment of post-traumatic tetanus remain the primary focus. which remains a significant public health challenge at present. In China, because tetanus booster vaccination is not yet widespread among adults, post-traumatic treatment and prophylaxis predominantly rely on passive immunotherapies for tetanus. Conventional passive immunizing agents include equine-derived tetanus antitoxin (TAT) and human tetanus immunoglobulin (HTIG). Although TAT remains widely used domestically, it is not recommended by the World Health Organization (WHO) due to safety concerns, while HTIG faces supply constraints and potential risks of pathogen transmission. The recent approval of the world′s first recombinant anti-tetanus toxin monoclonal antibody, developed through genetic recombination technology, offers a promising alternative to HTIG and TAT in clinical practice. This innovative agent has the potential to provide safer, more effective, and accessible tetanus prevention globally. To deepen the understanding of research progress in clinical applications of existing passive immunizing agents for tetanus, the authors reviewed the current application status of conventional agents and explored the key technical characteristics, neutralizing antigenic epitopes, and clinical application of the novel recombinant anti-tetanus toxin monoclonal antibody for passive immunotherapy for tetanus, providing scientific reference to improve the rational use of these agents and standardize post-traumatic tetanus prevention and treatment practices.

Objective:To analyze the characteristics of non-seroconverted cases after rabies vaccination and observe the effect of booster vaccination.Methods:A retrospective collection of data was conducted from March 2022 to March 2023 across 409 rabies vaccination clinics in 27 provinces in China, focusing on cases with rabies virus neutralizing antibody (RVNA) levels less than 0.5 IU/ml after vaccination.Results:A total of 77 cases were identified in whom seroconversion was not observed within 30 days post-vaccination with the rabies vaccine. The gender distribution was 51.9% male and 48.1% female, with ages ranging from 2 to 83 years old. Delayed vaccination was observed in 11 cases (14.3%), and 63 cases (81.8%) received human rabies immunoglobulin (HRIG) injections. None of the cases had a confirmed immunosuppressive disease or taking immunosuppressive drugs, and the body mass index (BMI) distribution ranged from 14.37 to 34.74 kg/m 2. Seventy-six cases seroconverted after 1 to 3 doses of rabies vaccines as a booster vaccination. One case that did not seroconvert after the initial booster vaccination seroconverted after receiving additional 2 doses of vaccine. All patients were followed up for one year, with no cases of rabies reported. Conclusions:The characteristics of cases that failed to seroconvert after the full course of rabies vaccination lacked specificity, and booster vaccination could lead to seroconversion.

Objective:The aim of this study was to explore the risk factors that affect implementation of the innovative technique of single-incision laparoscopic appendectomy (solo-SLA) without assistance in patients with complicated appendicitis, the goal being improving surgical success rates and reducing the incidence of complications.Methods:This was an observational study. Indications for solo-SLA surgery were as follows: (1) computed tomography or ultrasound findings suggestive of acute appendicitis, accompanied by a high white blood cell count and C-reactive protein concentration; (2) disease course exceeding 72 hours, standard anti-infection treatment ineffective, inflammatory reaction not localized, surgery mainly aimed at abscess drainage, and the appendix removed if indicated intraoperatively; (3) acute onset stabilized for more than 3 months after conservative treatment; and (4) recurrent chronic appendicitis. Relative contraindications comprised: (1) cardiopulmonary insufficiency, extremely high risk for general anesthesia for laparoscopic surgery; (2) severe coagulation dysfunction; and (3) imaging findings suggestive of formation of a peri-appendiceal abscess, stable after anti-infection treatment, and a tendency for the inflammatory reaction to localize. We retrospectively collected clinical data of 106 patients with complicated appendicitis who had undergone solo-SLA in the Department of Emergency Surgery, Peking University People's Hospital from February to October 2023. Preoperative computed tomography showed appendiceal fecaliths, blurring of the tissue surrounding fat, intra- and extra-luminal gas and exudate, peri-appendiceal abscess, ascites, and intestinal obstruction by appendicitis. The study cohort comprised 53 male and 53 female patients aged (41.4±17.4) years. The median body mass index was (24.2±3.6) kg/m 2 and median preoperative body temperature (37.3±0.9)℃ Appendicitis had been present for >3 days in 21 of the patients (19.8%) and the maximum diameter of the appendix was (12.4±3.8) mm. The efficacy of the surgery was assessed and logistic regression analysis used to explore the factors affecting the duration of the procedure. The relationship between the maximum diameter of the appendix and duration of surgery was non-linear and was explored using a logistic regression model with restricted cubic spline (RCS). Results:Only one patient required conversion to open surgery; all the other patients successfully completed solo-SLA with a median intraoperative blood loss of 10 (1-100) ml and a surgical time of (65.4±31.7) minutes. Pain scores on postoperative Day 1 and 7 were (3.4±3.2) points and (1.5±1.7) points, respectively. There were no significant postoperative complications .The postoperative hospital stay was (3.5±1.5) days and the interval to resuming normal activities 14 (2-40) days. According to univariate and multivariate analyses, disease course >3 days (OR=5.19, 95%CI: 1.59-16.98, P=0.006) and C-reactive protein >10 mg/L (OR=1.01,95%CI: 1.00-1.02, P=0.003) were independent risk factors for surgical duration >60 minutes, whereas the maximum diameter of the appendix was not independently associated with duration of surgery (OR=1.10, 95%CI: 0.97-1.25, P=0.119). RCS analysis results showed a "U-shaped" association between the maximum diameter of the appendix and duration of surgery, the inflection point of the RCS curve being at a diameter of 10 mm. When the maximum diameter of the appendix was <10 mm, increases in diameter were not associated with longer duration of surgery (OR=1.15,95%CI: 0.55-2.58, P=0.710); whereas when the diameter was ≥10 mm, the maximum diameter of the appendix was associated with increased duration of surgery (OR=1.20, 95% CI: 1.04-1.42, P=0.022). Conclusion:The solo-SLA procedure can be performed to treat complicated appendicitis. A disease course >3 days, C-reactive protein concentration >10 mg/L, and maximum diameter of the appendix ≥10 mm are all associated with greater difficulty of solo-SLA surgery.

Objective To develop a team collaborative protocol,based on the theory of the development of interprofessional collaborative team development(DICT),for early mobilisation of the patients with mechanical ventilation in the intensive care unit(ICU),hence to provide a standardised guidance on a multidisciplinary team with nurses as coordinators to implement the early mobilisation for ICU patients with mechanical ventilation and to improve the efficiency in patient mobilisation.Methods In September 2023,a preliminary draft of the collaborative team protocol based on ICTD was developed for early mobilisation of ICU patients with mechanical ventilation,based on literature review and current situation analysis.The status and influencing factors of multidisciplinary collaboration in early mobilisation for the patients with mechanical ventilation were identified.DICT framework was employed to develop the initial draft of protocol.From September to November 2023,Delphi expert consultation was employed and two rounds of expert consultation had been conducted before the final version of the protocol was drafted.Results A total of 21 experts participated in both rounds of consultation,with a 100.00%effective response rate of the questionnaires.Fifteen suggestions for modification were advised by the experts.The expert authority coefficient was 0.898,and the average coefficients of variation for the items from the two rounds of consultation were(0.14±0.05)and(0.12±0.06),respectively.The Kendall coordination coefficients for the two rounds were 0.198(P<0.001)and 0.256(P<0.001),respectively.The final protocol included 3 primary items(assessment and exploration,collaboration and integration,feedback and adjustment),13 secondary items and 57 tertiary items.Conclusion The team collaborative protocol for early mobilisation of ICU patients with mechanical ventilation,based on the DICT theory,is scientifically reliable.It provides a guidance and a reference for multidisciplinary teams in implementation of early mobilisation for ICU patients with mechanical ventilation..

Objective:The aim of this study was to explore the risk factors that affect implementation of the innovative technique of single-incision laparoscopic appendectomy (solo-SLA) without assistance in patients with complicated appendicitis, the goal being improving surgical success rates and reducing the incidence of complications.Methods:This was an observational study. Indications for solo-SLA surgery were as follows: (1) computed tomography or ultrasound findings suggestive of acute appendicitis, accompanied by a high white blood cell count and C-reactive protein concentration; (2) disease course exceeding 72 hours, standard anti-infection treatment ineffective, inflammatory reaction not localized, surgery mainly aimed at abscess drainage, and the appendix removed if indicated intraoperatively; (3) acute onset stabilized for more than 3 months after conservative treatment; and (4) recurrent chronic appendicitis. Relative contraindications comprised: (1) cardiopulmonary insufficiency, extremely high risk for general anesthesia for laparoscopic surgery; (2) severe coagulation dysfunction; and (3) imaging findings suggestive of formation of a peri-appendiceal abscess, stable after anti-infection treatment, and a tendency for the inflammatory reaction to localize. We retrospectively collected clinical data of 106 patients with complicated appendicitis who had undergone solo-SLA in the Department of Emergency Surgery, Peking University People's Hospital from February to October 2023. Preoperative computed tomography showed appendiceal fecaliths, blurring of the tissue surrounding fat, intra- and extra-luminal gas and exudate, peri-appendiceal abscess, ascites, and intestinal obstruction by appendicitis. The study cohort comprised 53 male and 53 female patients aged (41.4±17.4) years. The median body mass index was (24.2±3.6) kg/m 2 and median preoperative body temperature (37.3±0.9)℃ Appendicitis had been present for >3 days in 21 of the patients (19.8%) and the maximum diameter of the appendix was (12.4±3.8) mm. The efficacy of the surgery was assessed and logistic regression analysis used to explore the factors affecting the duration of the procedure. The relationship between the maximum diameter of the appendix and duration of surgery was non-linear and was explored using a logistic regression model with restricted cubic spline (RCS). Results:Only one patient required conversion to open surgery; all the other patients successfully completed solo-SLA with a median intraoperative blood loss of 10 (1-100) ml and a surgical time of (65.4±31.7) minutes. Pain scores on postoperative Day 1 and 7 were (3.4±3.2) points and (1.5±1.7) points, respectively. There were no significant postoperative complications .The postoperative hospital stay was (3.5±1.5) days and the interval to resuming normal activities 14 (2-40) days. According to univariate and multivariate analyses, disease course >3 days (OR=5.19, 95%CI: 1.59-16.98, P=0.006) and C-reactive protein >10 mg/L (OR=1.01,95%CI: 1.00-1.02, P=0.003) were independent risk factors for surgical duration >60 minutes, whereas the maximum diameter of the appendix was not independently associated with duration of surgery (OR=1.10, 95%CI: 0.97-1.25, P=0.119). RCS analysis results showed a "U-shaped" association between the maximum diameter of the appendix and duration of surgery, the inflection point of the RCS curve being at a diameter of 10 mm. When the maximum diameter of the appendix was <10 mm, increases in diameter were not associated with longer duration of surgery (OR=1.15,95%CI: 0.55-2.58, P=0.710); whereas when the diameter was ≥10 mm, the maximum diameter of the appendix was associated with increased duration of surgery (OR=1.20, 95% CI: 1.04-1.42, P=0.022). Conclusion:The solo-SLA procedure can be performed to treat complicated appendicitis. A disease course >3 days, C-reactive protein concentration >10 mg/L, and maximum diameter of the appendix ≥10 mm are all associated with greater difficulty of solo-SLA surgery.

Objective To develop a team collaborative protocol,based on the theory of the development of interprofessional collaborative team development(DICT),for early mobilisation of the patients with mechanical ventilation in the intensive care unit(ICU),hence to provide a standardised guidance on a multidisciplinary team with nurses as coordinators to implement the early mobilisation for ICU patients with mechanical ventilation and to improve the efficiency in patient mobilisation.Methods In September 2023,a preliminary draft of the collaborative team protocol based on ICTD was developed for early mobilisation of ICU patients with mechanical ventilation,based on literature review and current situation analysis.The status and influencing factors of multidisciplinary collaboration in early mobilisation for the patients with mechanical ventilation were identified.DICT framework was employed to develop the initial draft of protocol.From September to November 2023,Delphi expert consultation was employed and two rounds of expert consultation had been conducted before the final version of the protocol was drafted.Results A total of 21 experts participated in both rounds of consultation,with a 100.00%effective response rate of the questionnaires.Fifteen suggestions for modification were advised by the experts.The expert authority coefficient was 0.898,and the average coefficients of variation for the items from the two rounds of consultation were(0.14±0.05)and(0.12±0.06),respectively.The Kendall coordination coefficients for the two rounds were 0.198(P<0.001)and 0.256(P<0.001),respectively.The final protocol included 3 primary items(assessment and exploration,collaboration and integration,feedback and adjustment),13 secondary items and 57 tertiary items.Conclusion The team collaborative protocol for early mobilisation of ICU patients with mechanical ventilation,based on the DICT theory,is scientifically reliable.It provides a guidance and a reference for multidisciplinary teams in implementation of early mobilisation for ICU patients with mechanical ventilation..

Tetanus is a potentially life-threatening neurological condition, and the prevention and treatment of post-traumatic tetanus remain the primary focus. which remains a significant public health challenge at present. In China, because tetanus booster vaccination is not yet widespread among adults, post-traumatic treatment and prophylaxis predominantly rely on passive immunotherapies for tetanus. Conventional passive immunizing agents include equine-derived tetanus antitoxin (TAT) and human tetanus immunoglobulin (HTIG). Although TAT remains widely used domestically, it is not recommended by the World Health Organization (WHO) due to safety concerns, while HTIG faces supply constraints and potential risks of pathogen transmission. The recent approval of the world′s first recombinant anti-tetanus toxin monoclonal antibody, developed through genetic recombination technology, offers a promising alternative to HTIG and TAT in clinical practice. This innovative agent has the potential to provide safer, more effective, and accessible tetanus prevention globally. To deepen the understanding of research progress in clinical applications of existing passive immunizing agents for tetanus, the authors reviewed the current application status of conventional agents and explored the key technical characteristics, neutralizing antigenic epitopes, and clinical application of the novel recombinant anti-tetanus toxin monoclonal antibody for passive immunotherapy for tetanus, providing scientific reference to improve the rational use of these agents and standardize post-traumatic tetanus prevention and treatment practices.

Objective:To analyze the characteristics of non-seroconverted cases after rabies vaccination and observe the effect of booster vaccination.Methods:A retrospective collection of data was conducted from March 2022 to March 2023 across 409 rabies vaccination clinics in 27 provinces in China, focusing on cases with rabies virus neutralizing antibody (RVNA) levels less than 0.5 IU/ml after vaccination.Results:A total of 77 cases were identified in whom seroconversion was not observed within 30 days post-vaccination with the rabies vaccine. The gender distribution was 51.9% male and 48.1% female, with ages ranging from 2 to 83 years old. Delayed vaccination was observed in 11 cases (14.3%), and 63 cases (81.8%) received human rabies immunoglobulin (HRIG) injections. None of the cases had a confirmed immunosuppressive disease or taking immunosuppressive drugs, and the body mass index (BMI) distribution ranged from 14.37 to 34.74 kg/m 2. Seventy-six cases seroconverted after 1 to 3 doses of rabies vaccines as a booster vaccination. One case that did not seroconvert after the initial booster vaccination seroconverted after receiving additional 2 doses of vaccine. All patients were followed up for one year, with no cases of rabies reported. Conclusions:The characteristics of cases that failed to seroconvert after the full course of rabies vaccination lacked specificity, and booster vaccination could lead to seroconversion.

Objective To investigate the effect of4-amino-2-trifluoromethyl-phenyl retinate(ATPR)on acute liver injury induced by lipopolysaccharide(LPS)in C57BL/6 mice and its related mechanism.Methods Fifteen 6-week-old male C57BL/6 strain mice were randomly divided into normal group,model group and ATPR group,with 5 mice in each group.Mice in the ATPR group were intraperitoneally injected with ATPR(15 mg/kg·d),and normal group and model group were given solvent.After continuous administration for one week,model group and ATPR group were intraperitoneally injected with LPS(6 mg/kg),and all mice were sacrificed 6 hours later.The contents of Alanine aminotransferase(ALT)and Aspartate aminotransferase(AST)in serum of mice were detec-ted.The mRNA levels of Interleukin-6(IL-6)and Tumor necrosis factor-alpha(TNF-α)were detected by qPCR.Hematoxylin-eosin(H&E)staining was used to observe the histopathological changes of liver in mice.The ultra-structural changes of mouse hepatocytes were observed by Transmission electron microscope(TEM).The expres-sion levels of mitochondrial damage-related proteins FUNDC1 and OPA1 and autophagy related proteins LC3B,P62,Beclin1 and ATG5 were detected by Western blot.Results Compared with the normal group,the content of ALT and AST in serum and the mRNA levels of IL-6 and TNF-α in liver tissue increased in the model group,and the changes were reversed in the ATPR group.H&E staining showed that the hepatic lobule structure was normal in the normal group,the hepatic cords were arranged radially,there was no hyperemia and inflammatory cell infiltra-tion,and the hepatocyte boundary was clear.In the model group,the intercellular space of liver was enlarged,the arrangement of hepatic cords was disordered,and inflammatory cells infiltrated.In the ATPR group,the intercellu-lar space of liver and the structure of hepatic cords were restored,and the inflammatory cell infiltration was less.TEM showed that the damaged mitochondria and lipid droplet accumulation in the hepatocytes of mice in the model group were compared with that in the normal group,and the morphology and quantity of mitochondria and lipid droplet in the hepatocytes of mice in the ATPR group tended to be normal.Western blot showed that compared with the normal group,the expression of FUNDC1 protein in the liver tissues of mice in the model group increased,the expression of OPA1 protein decreased,the ratio of LC3B Ⅱ to LC3B Ⅰ decreased,the expression of P62 protein in-creased,the expression of Beclin1 and ATG5 protein decreased,and the above changes were reversed in the ATPR group.Conclusion ATPR alleviates acute liver injury induced by lipopolysaccharide in mice by promoting autoph-agy.

ObjectiveTo quantitatively investigate the changes in the total volume and contour density of hepatic oval cells （HOC） in hepatic lobules of rats with carbon tetrachloride （CCl₄）-induced hepatic fibrosis. MethodsA total of 11 healthy male Sprague-Dawley rats were randomly divided into control group with 5 rats and hepatic fibrosis group with 6 rats， and CCl₄ and olive oil suspension were injected subcutaneously twice a week， 3 mL/kg each time. After five weeks of hepatic fibrosis modeling， five liver tissue blocks with a size of about 1 mm³ were randomly selected from the liver of each rat to prepare one Epon812 epoxy resin-embedded ultrathin section， and the stereological method and transmission electron microscopy were used for the quantitative analysis of the total volume and contour density of HOC in the hepatic lobules of rats. In addition， four liver tissue blocks with a thickness of 2 mm were randomly selected from the remaining liver of each rat to prepare two paraffin-embedded Masson staining sections， and the degree of liver fibrosis in each rat was qualitatively evaluated according to the Metavir staging criteria for liver fibrosis. The independent-samples t test was used for comparison of continuous data between groups. ResultsThe quantitative stereological analysis showed that the total volume of HOC in hepatic lobules was 15.40±7.63 mm³ in the control group and 146.80±114.00 mm³ in the liver fibrosis group， and compared with the control group， the total volume of HOC in hepatic lobules of rats in the liver fibrosis group was significantly increased by 8.53 times （t=-2.551， P=0.031）； the contour density of HOC in hepatic lobules was 56.20±40.40 in the control group and 566.50±317.00 in the liver fibrosis group， and compared with the control group， the contour density of HOC in hepatic lobules of rats in the liver fibrosis group was significantly increased by 9.08 times （t=-3.539， P=0.006）. Qualitative observation showed that liver fibrosis stage of rats reached stage Ⅱ-Ⅲ according to the Metavir scoring criteria， and massive proliferation of HOC was observed around the proliferation site of hepatic stellate cells in the perisinusoidal space of rats. ConclusionCCl₄ induces significant proliferation of HOC in hepatic lobules of rats with liver fibrosis.