[Interpretation of the National Regulation for the Rabies Exposure Prophylaxis (2023 Edition)].

Rabies is one of the important zoonotic infectious diseases, with a mortality rate of almost 100%. Rabies is a vaccine preventable disease, and proper rabies exposure prophylaxis can effectively prevent the occurrence of human rabies. In recent years, there has been significant progress in clinical research on the rabies exposure prophylaxis both domestically and internationally. World Health Organization (WHO) released the Rabies Vaccine: WHO Position Paper-April 2018. In order to guide medical institutions of all levels in rabies exposure prophylaxis, the National Administration of Disease Prevention and Control, in conjunction with the National Health Commission of the People's Republic of China, organized the Rabies Vaccine Working Group of the National Immunization Program Technical Working Group and invited experts to revise and issue the National Regulation for the Rabies Exposure Prophylaxis (2023 Edition). This article compares the National Regulation for the Rabies Exposure Prophylaxis (2009 Edition) and interprets the updated key points and supporting basis of the new version of the guidelines to guide clinical application and implementation.

[Progress and prospect of clinical application of anti-rabies virus monoclonal antibody preparation].

Rabies is a severe infectious disease caused by the rabies virus, which seriously damages the central nervous system. Once it occurs, the fatality rate is close to 100%. The World Health Organization's position paper on rabies vaccines recognizes that rabies immunoglobulin (RIG) should be used for post-exposure prophylaxis (PEP) in all category Ⅲ exposure for the first time, as well as in category Ⅱ exposure that suffer from severe immune deficiency, long-term massive use of immunosuppressants, and head and face exposure. The anti-rabies virus monoclonal antibody has high purity and specific activity, can be produced on a sustainable scale, and has no risk of blood source virus contamination. Preclinical pharmacodynamic studies and clinical trial results of the anti-rabies virus monoclonal antibody preparation have confirmed that the preparation has a broad-spectrum neutralization effect on the rabies virus. Additionally, its combined application with the vaccine has little impact on the active immunity of the vaccine. Therefore, the anti-rabies virus monoclonal antibody preparation shows great potential for clinical application in PEP.

[Treatment and prognosis analysis of 488 patients with FIGO 2018 stage â ¢c squamous cervical cancer].

Objective: To analyze the treatment and prognosis of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage Ⅲc cervical squamous cell carcinoma. Methods: A total of 488 patients at Zhejiang Cancer Hospital between May, 2013 to May, 2015 were enrolled. The clinical characteristics and prognosis were compared according to the treatment mode (surgery combined with postoperative chemoradiotherapy vs radical concurrent chemoradiotherapy). The median follow-up time was (96±12) months ( range time from 84 to 108 months). Results: (1) The data were divided into surgery combined with chemoradiotherapy group (surgery group) and concurrent chemoradiotherapy group (radiotherapy group), including 324 cases in the surgery group and 164 cases in the radiotherapy group. There were significant differences in Eastern Cooperation Oncology Group (ECOG) score, FIGO 2018 stage, large tumors (≥4 cm), total treatment time and total treatment cost between the two groups (all P<0.01). (2) Prognosis: ① for stage Ⅲc1 patients, there were 299 patients in the surgery group with 250 patients survived (83.6%). In the radiotherapy group, 74 patients survived (52.9%). The difference of survival rates between the two groups was statistically significant (P<0.001). For stage Ⅲc2 patients, there were 25 patients in surgery group with 12 patients survived (48.0%). In the radiotherapy group, there were 24 cases, 8 cases survived, the survival rate was 33.3%. There was no significant difference between the two groups (P=0.296). ② For patients with large tumors (≥4 cm) in the surgery group, there were 138 patients in the Ⅲc1 group with 112 patients survived (81.2%); in the radiotherapy group, there were 108 cases with 56 cases survived (51.9%). The difference between the two groups was statistically significant (P<0.001). Large tumors accounted for 46.2% (138/299) vs 77.1% (108/140) in the surgery group and radiotherapy group. The difference between the two groups was statistically significant (P<0.001). Further stratified analysis, a total of 46 patients with large tumors of FIGO 2009 stage Ⅱb in the radiotherapy group were extracted, and the survival rate was 67.4%, there was no significant difference compared with the surgery group (81.2%; P=0.052). ③ Of 126 patients with common iliac lymph node, 83 patients survived, with a survival rate of 65.9% (83/126). In the surgery group, 48 patients survived and 17 died, with a survival rate of 73.8%. In the radiotherapy group, 35 patients survived and 26 died, with a survival rate of 57.4%. There were no significant difference between the two groups (P=0.051). (3) Side effects: the incidence of lymphocysts and intestinal obstruction in the surgery group were higher than those in the radiotherapy group, and the incidence of ureteral obstruction and acute and chronic radiation enteritis were lower than those in the radiotherapy group, and there were statistically significant differences (all P<0.01). Conclusions: For stage Ⅲc1 patients who meet the conditions for surgery, surgery combined with postoperative adjuvant chemoradiotherapy and radical chemoradiotherapy are acceptable treatment methods regardless of pelvic lymph node metastasis (excluding common iliac lymph node metastasis), even if the maximum diameter of the tumor is ≥4 cm. For patients with common iliac lymph node metastasis and stage Ⅲc2, there is no significant difference in the survival rate between the two treatment methods. Based on the duration of treatment and economic considerations, concurrent chemoradiotherapy is recommended for the patients.

[Four-steps surgery for infected pancreatic necrosis based on "Step-up" strategy: a retrospective study].

Objective: To examine the effect of the "four-steps" treatment on infectious pancreatic necrosis(IPN). Methods: The data of 207 patients who were diagnosed with IPN from January 2013 to December 2017 at Department of Pancreaticobiliary Surgery, the First Affiliated Hospital of Harbin Medical University were analyzed retrospectively. Among 207 patients, 132(63.8%) were males and 75(36.2%) were females. The median age was 45 years old (range: 19 to 80 years old). One hundred and fifty-eight patients(76.3%) suffered severe acute pancreatitis and 49 patients(23.7%) suffered moderately severe acute pancreatitis. Percutaneous catheter drainage(PCD) was performed on all the patients(Step 1). Patients received "four-steps" minimally invasive treatment strategy in step-up group(173 patients). The following steps after PCD were mini-incision access pancreatic necrosectomy(MIAPN) (Step 2), sinus tract endoscopic debridement and(or) PCD for residual infections(Step 3) and finally conventional open pancreatic necrosectomy(OPN) (Step 4). Patients(34 cases) received conventional open pancreatic necrosectomy after invalided PCD in OPN group. The perioperative parameters and prognosis were compared between Step-up group and OPN group. Normally distributed quantitative variables were analyzed by t-test, non-normally distributed quantitative variables were analyzed by Wilcoxon chi-square test and categorical variables were analyzed by χ(2) test or Fisher exact test, respectively. Results: The basic characteristics of the two groups of patients were similar, but the referral rate of patients and the rate of preoperative 3 days organ failure in the OPN group were significantly higher than those of step-up group patients(47.1% vs. 28.9%, χ(2)=4.313, P=0.038; 26.5% vs. 9.2%, χ(2)=2.819, P=0.011). The frequency of PCD and the number of PCD tube (root) were less than those in the step-up group(1(1) vs. 2(1), Z=-3.373, P=0.018; 2(1) vs. 3(2), Z=-2.208, P=0.027). Compared with the OPN group, the interval time from onset to surgery and the MIAPN operation time were significantly shorter in the step-up group(29(15) days vs. 36(17)days, Z=-0.567, P=0.008; 58(27)minutes vs. 90(56)minutes, Z=-3.908, P<0.01); postoperative mortality was lower(5.8% vs.17.6%, χ(2)=4.070, P=0.044); the overall incidence of postoperative complications was reduced(23.1% vs. 55.9%, χ(2)=14.960, P<0.01) and the incidence of new-onset organ failure was decreased after operation in the step-up group(37.5% vs.47.4%, χ(2)=7.133, P=0.007). The incidence of local abdominal complications (pancreatic fistula, intra-abdominal hemorrhage, gastrointestinal fistula) showed no significant difference between the two groups (P>0.05). Fewer patients required ICU treatment after operation in the step-up group compared with OPN group(22.0% vs. 44.1%, χ(2)=6.204, P=0.013). Patients in the Step-up group has shorter hospital stay than patients in OPN group (46(13) days vs. 52(13)days, Z=-1.993, P=0.046). Conclusions: The clinical effects of "four-steps" exhibited the superiority of minimally invasive treatment of IPN.And MIAPN is a simple, safe and effective procedure to remove pancreatic necrotic tissue and decrease complications.

[Classification and production process of human vaccine].

Human vaccine is the most effective tool to prevent infectious diseases. At present, there are dozens of vaccines that can prevent dozens of infectious diseases. Vaccines for human use include vaccines that do not contain living micro-organisms (inactivated vaccines, toxoid vaccines, component vaccines), and vaccines that contain living micro-organisms (live attenuated vaccines and vector vaccines). The research and development of human vaccine includes clinical trial, process development and test method research, and the production process of human vaccine is very important for the preparation of high-quality and reliable vaccine. In this paper, the development of human vaccines, the production process and the characteristics of various human vaccines are reviewed.

[Research progress of tetanus antibody detection technology in China].

The situation of prevention of non-neonatal tetanus in China is severe. Strengthening the active immunization with tetanus toxoid vaccine (TTCV) is the key to prevent the non-neonatal tetanus. Through the detection of tetanus antibody (TAB), the immune status of individual can be determined, so as to implement the active immunization of TTCV correctly. The research on TAB detection technology is stagnant in aboard, but still in a development process in China since there is a realistic demand for TAB detection. This review collects relatively limited data of TAB detection technology in China, and summarizes the techniques such as mice toxin neutralization test (MTNT), indirect hemagglutination assay (IHA), double agar gel immune diffusion test (Rubin method), enzyme-linked immunosorbent assay (ELISA) and colloidal gold (CG), in order to provide a comprehensive basis for domestic TAB detection. The TAB detection technology in China has not yet achieved international recognition due to the lack of comparative study of domestic and international institutions and reference reagents. The special domestic situation of tetanus prevention makes the research of TAB detection technology have a certain practical significance, and rapid detection reagents such as ELISA and CG method have a certain application value in China.

[Expert consensus on rabies exposure prophylaxis].

Rabies is a zoonotic infectious disease caused by lyssavirus and characterized by central nervous system symptoms. The fatality rate of rabies is almost 100%. About 59 000 cases die of rabies worldwide every year, mainly in Asia and Africa. China is an epidemic country of rabies. Grade II and III exposures are the main types of rabies exposures in China. Standardized post-exposure prophylaxis (PEP) can prevent rabies almost 100%. Human Rabies Vaccine Technical Working Group, National Immunization Advisory Committee and invited experts reached an expert consensus on PEP by referring to the World Health Organization's position paper on rabies vaccine in 2018 and related research progress in recent.

[Clinical analysis of small incision minimally invasive approach in treatment of infected pancreatic necrosis].

Objective: To investigate the safety and efficiency of small incision minimally invasive approach pancreatic necrosectomy in the treatment of infected pancreatic necrosis. Methods: The data of 164 patients who underwent small incision minimally invasive approach pancreatic necrosectomy for infected pancreatic necrosis at Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University from January 2012 to December 2016 were analyzed retrospectively.Among 164 patients, there were 102 male and 62 female patients.The median age was 46 years(ranging from 19 to 79 years). One hundred and one patients(61.6%) suffered from severe acute pancreatitis and 63 patients(38.4%) suffered from moderately severe acute pancreatitis.Following step-up approach principle, the surgical procedures were performed for 131 patients(79.9%) who suffered from sepsis which could not be alleviated via percutaneous catheter drainage(PCD). The other 33 patients(20.1%) who did not undergo PCD directly took small incision minimally invasive approach pancreatic necrosectomy.Preoperative CT images were used to determine the location of the lesion.The PCD puncture points or the points where the abscess was closest to the skin were chosen as the incision.Gradually, the small incision minimally invasive approach pancreatic necrosectomy were performed via cutting all layers into the abscess. Results: The median time from the onset of symptom to first operation was 32 days(ranging from 23 to 45 days). The average hospital stay was 46 days(ranging from 29 to 103 days). The average number of drainage tubes placed was 4 pieces(ranging from 2 to 8 pieces). Ninety-two patients(56.0%) underwent minimal access retroperitoneal pancreatic necrosectomy. Thirty-six patients(22.0%) underwent minimal invasive approach lesser omentum sac pancreatic necrosectomy.Thirty-six patients(22.0%) underwent minimal invasive approach lesser omentum sac pancreatic necrosectomy combined with minimal access retroperitoneal pancreatic necrosectomy.A total of 148 cases(90.2%) were cured via minimally invasive approach pancreatic necrosectomy, 8 cases(4.9%) were cured after transfering to open pancreatic necrosectomy.The cure rate was 95.1%(156/164). The mainly postoperative complications included pancreatic fistula(25 cases), intra-abdominal hemorrhage(10 cases), gastric fistula (2 cases), duodenal fistula(4 cases) and colonic fistula(3 cases). The overall incidence rate of complications was 26.8%(44/164). Eight cases were dead after surgery and the in-hospital mortality was 4.9%(8/164). Conclusion: In summary, small incision minimally invasive approach pancreatic necrosectomy is an effective way to clean up necrotic tissue, improve the drainage, reduce complications in dealing with infected pancreatic necrosis.

[Curative effect analysis of postoperative concurrent chemoradiotherapy on early-stage cervical cancer patients with intermediate-risk factors].

Objective: To compare the curative effect of postoperative concurrent chemoradiotherapy (CCRT) and radiation therapy (RT) alone on early-stage cervical cancer patients with intermediate-risk factors. Methods: Clinical data of patients with early stage (ⅠB-ⅡA) cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy in Zhejiang Cancer Hospital between January 2008 and December 2011 were retrospectively analyzed. Cervical squamous cell carcinoma patients with more than two intermediate-risk factors, including lymphatic vascular infiltration, depth of cervical stromal infiltration >1/2 cm or tumor size >4 cm, were screened. Among them, 80 patients were divided into the RT group, 137 patients were divided into the CCRT group. The survivals of these patients were analyzed. Results: At the end of the follow-up period, a total of 22 patients were dead, one patient was alive with neoplasm. There were 23 patients who occurred recurrence/ metastasis, 14 of them were in the RT group and 9 were in the CCRT group. The 5-year progression free survival (PFS) and 5-year overall survival (OS) rate of the entire cohort were 89.9% and 89.8%, respectively. The 5-year PFS rate of RT group was 82.4%, the 5-year PFS rate of CCRT group was 94.1%, and the difference between the two groups was statistically significant (P=0.013). The 5-year OS rate of RT group was 85.1%, the 5-year OS rate of CCRT group was 92.7%, and the difference between the two groups was statistically significant (P=0.049). Univariate analysis showed that therapeutic modality was associated with the 5-year DFS and OS of early-stage cervical cancer patients with intermediate-risk factors (P<0.05). The results of multivariate analysis showed that therapeutic modality was an independent prognostic factor of favorable PFS (RR=3.741, 95% CI: 1.506-9.289, P=0.004) and OS (RR=2.754, 95%CI=1.143-6.637, P=0.024). Neither of the two groups occurred severe anemia. However, the incidence of mild and moderate anemia in the CCRT group was higher than that of RT group (P<0.001). The incidence of leukocytopenia severer than grade Ⅲ in the CCRT group was significantly higher than that of RT group (P<0.001). However, the patients could recover quickly with the treatment of granulocyte colony-stimulating factor. Conclusion: Postoperative CCRT improves the survival of early stage cervical cancer patients with two or more intermediate-risk factors.

[Expert consensus on the diagnosis and treatment of cryptococcal meningitis].

Cryptococcal meningitis is a common and refractory central nervous system infection, with high rates of mortality and disability. The experts of the Society of Infectious Diseases of Chinese Medical Association have reached this consensus after a thorough discussion. Based on the current situation of cryptococcal meningitis in China, the management of cryptococcal meningitis includes 6 aspects: introduction, microorganism identification, clinical manifestations and diagnosis, principles of antifungal therapy, treatment of refractory and recurrent meningitis, treatment of intracranial hypertension. There is not a separate consensus on human immunodeficiency virus (HIV) infection in patients with cryptococcal meningitis. This article focuses on different antifungal regimens and reducing intracranial pressure by reference to Infectious Disease Society of America (IDSA) guidelines. The importance of early diagnosis, combined long-term antifungal therapy, control of intracranial hypertension are emphasized.

[Research advances in anatomical study on the diffusion routs of acute pancreatitis].

The retroperitoneum space comprises anterior pararenal space, perirenal space and posterior pararenal space. Pancreas is a retroperitoneal organ and located in the anterior pararenal space of the retroperitoneum. Left and right sides anterior pararenal space are potentially communicated, which contains many adipose tissues and a little connective tissues. The exacerbation of acute pancreatitis results in the lesion spreading into adjacent area of pancreas in the retroperitoneal space. In addition, the lesion could spread into bare area of stomach, posterior colonic region, subperitoneal space and pelvic retroperitoneal space through the same anatomical space or communicating space. Due to the fascia destruction by pancreatic enzymes or the lesion directly diffuse through the weak fascia, the lesion could also diffuse across fascia to perirenal space, posterior pararenal space, the peritoneal cavity and abdominal wall. Finally, a series of complications are developed. The diffusion paths of acute pancreatitis are complex and diverse. Familiarity with these diffusion paths is useful for determining the severity and guiding therapy.

[Commuting mode specific exposure to PM(2.5) in urban area of Guangzhou].

Objective: To find the differences in PM(2.5) exposure level in the context of four commuting modes (by walk, bicycle, bus and subway) in Guangzhou. Methods: The PM(2.5) exposure assessment was carried out from January to December 2015 in Guangzhou. PM(2.5) was measured by using SidePak individual dust meter (AM510, TSI Inc. USA) with time interval of 1 minute. Our measurement was taken on Monday, Wednesday, Friday and Sunday in the second week of each month and the samples were collected in the morning (07:00-09:00), afternoon (11:00-13:00) and evening (17:00-19:00). Results: A total of 284 air samples during walking, 281 air samples during bicycle riding, 278 air samples in bus, and 280 air samples in subway were collected. The median PM(2.5) concentrations exposed during walking, during bicycle riding, in bus and in subway were 38.4, 38.6, 23.3 and 24.1 µg/m(3), respectively, which were positive correlated with exposure concentration in fixed surveillance sites. The exposure level was lowest in summer, and highest in winter. The median of one-way exposure level to PM(2.5) from high to low were as follows: 21.0 µg for bicycle riding, 20.1 µg for walking, 5.1 µg for taking bus and 2.6 µg for taking subway. The season and time specific one-way exposure levels to PM(2.5) of four commuting modes were consistent. Conclusions: The exposure level to PM(2.5) was obviously higher during walking and bicycle riding than that in bus and subway. The exposure level to PM(2.5) during walking was higher than that during bicycle riding, in bus and in subway.