BACKGROUND:Early identification of patients requiring ventilator support will be beneficial for the outcomes of botulism.The present study aimed to establish a new scoring system to predict mechanical ventilation(MV)for botulism patients. METHODS:A single-center retrospective study was conducted to identify risk factors associated with MV in botulism patients from 2007 to 2022.Univariate analysis and multivariate logistic regression analysis were used to screen out risk factors for constructing a prognostic scoring system.The area under the receiver operating characteristic(ROC)curve was calculated. RESULTS:A total of 153 patients with botulism(66 males and 87 females,with an average age of 43 years)were included.Of these,49 patients(32.0%)required MV,including 21(13.7%)with invasive ventilation and 28(18.3%)with non-invasive ventilation.Multivariate analysis revealed that botulinum toxin type,pneumonia,incubation period,degree of hypoxia,and severity of muscle involvement were independent risk factors for MV.These risk factors were incorporated into a multivariate logistic regression analysis to establish a prognostic scoring system.Each risk factor was scored by allocating a weight based on its regression coefficient and rounded to whole numbers for practical utilization([botulinum toxin type A:1],[pneumonia:2],[incubation period≤1 day:2],[hypoxia<90%:2],[severity of muscle involvement:grade II,3;grade III,7;grade IV,11]).The scoring system achieved an area under the ROC curve of 0.82(95%CI 0.75-0.89,P<0.001).At the optimal threshold of 9,the scoring system achieved a sensitivity of 83.7%and a specificity of 70.2%. CONCLUSION:Our study identified botulinum toxin type,pneumonia,incubation period,degree of hypoxia,and severity of muscle involvement as independent risk factors for MV in botulism patients.A score≥9 in our scoring system is associated with a higher likelihood of requiring MV in botulism patients.This scoring system needs to be validated externally before it can be applied in clinical settings.

Objective:To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years.Methods:An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster.Results:The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A′s 44.79 (36.94-54.30) ( P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A′s 15.71 (13.24-18.63) ( P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion:Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

Objective:To explore the role and mechanism of nuclear receptor subfamily 4 group A member 1 ( NR4A1) in suppressing cisplatin nephrotoxicity. Methods:The expression of NR4A1 gene in renal cell subpopulations was analyzed using the "Tabula-muris" single cell transcriptome sequencing database. NR4A1 gene was over-expressed by lentivirus infection in HK-2 cell line and primary renal proximal tubular epithelial cells. Cell counting kit-8 was used to detect the cytotoxicity of cisplatin. The cell death ratio was analyzed using propidium iodide (PI) staining by flow cytometry. The expression of NR4A1 and nuclear factor erythroid 2-related factor 2 ( NRF2) was detected by real-time fluorescent quantitative PCR and Western blotting. Ferroptosis was analyzed by detecting the contents of malondialdehyde (MDA), oxidized glutathione (GSSG) and lipid reactive oxygen species (ROS). Results:The single cell transcriptome sequencing database showed that NR4A1 gene was the lowest expression in renal proximal tubular epithelial cell subsets. Cisplatin (50 μmol/L or 100 μmol/L) could significantly induce MDA, GSSG and lipid ROS production in renal proximal tubular epithelial cells (all P<0.01), and higher cisplatin concentration accompanied with a more increase of MDA, GSSG and lipid ROS. Compared with the control HK-2 cells, the lipid ROS content and iron ion content of HK-2 cells over-expressing NR4A1 were significantly lower (all P<0.01), and the over-expression of NR4A1 inhibited cisplatin-induced cytotoxicity and ferroptosis in renal proximal tubular epithelial cells. Mechanistically, NR4A1 up-regulated the expression of anti-ferroptosis gene NRF2 in proximal renal tubular epithelial cells ( P<0.01). Furthermore, single cell data analysis showed that, similar to the expression of NR4A1 in renal tissue subsets, NRF2 was also the lowest in renal proximal tubular epithelial cells. Conclusions:Cisplatin can induce ferroptosis of renal proximal tubular epithelial cells in a dose-dependent manner. NR4A1 can inhibit cisplatin-induced ferroptosis by up-regulating NRF2 in renal proximal tubular epithelial cells, thereby alleviating the cytotoxicity of cisplatin.

Objective:To explore the effects of non-suicidal self-injury on suicidal ideation in adolescents with depressive disorder, and the mediating role of rumination and depression between them.Methods:A sample of 397 depressive disorder adolescents were recruited to complete the adolescent non-suicidal self-injury behaviour questionnaire, ruminative responses scale (RRS), self-rating depression scale (SDS), and Beck scale for suicide ideation-Chinese version(BSI-CV). All data processing and analysis were performed using SPSS 23.0.The mediating effect was tested by correlation analysis and Bootstrap analysis.Results:The non-suicidal self-injury score was (29.192±11.281), the rumination score was (65.036±12.284), the depression score was (75.770±11.278), and the suicidal ideation score was (40.681±11.626). Non-suicidal self-injury was significantly and positively correlated with suicidal ideation( r=0.403, P<0.01), rumination and depression( r=0.332, 0.470, both P<0.01). Rumination was significantly and positively correlated with depression and suicidal ideation( r=0.549, 0.181, both P<0.05). Depression was significantly and positively correlated with suicidal ideation( r=0.313, P<0.01). The direct effect value of non-suicidal self-injury on suicidal ideation was 0.341(95% CI=0.238-0.444), the indirect effect of non-suicidal self-injury on suicidal ideation through two pathways, the separate mediating effect value of depression was 0.057(95% CI=0.077-0.114), and the chain mediating effect value of rumination and depression was 0.026(95% CI=0.004-0.057). Conclusion:Non-suicidal self-injury can directly affect suicidal ideation of depressive disorder adolescents and indirectly through rumination and depression.

The School of Basic Medical Sciences of North Sichuan Medical University explores the reform of the basic medicine teacher's ability cultivation from the following aspects, including the classroom teaching quality, practical teaching skills, the innovation ability of scientific research, the basic and clinical integration and so on. Practice has proved that these reforms have greatly improved the quality of teachers' abilities and also the quality of education and teaching.

Objective:To understand the basic situation of noise hazards in wood furniture manufacturing, stone processing and special equipment manufacturing industries in Shenzhen City, and to provide basis for preventing and controlling noise hazards.Methods:In August 2019, stratified random sampling ws used to select 21 wood funiture manafacturing, 15 stone processing and 24 special equipment manufactruing as survey object. Through the methods of occupational health field investigation, noise intensity measurement and occupational health examination data collection, the noise hazards of 60 enterprises in three industries were statistically analyzed.Results:There were 154, 44 and 113 noise detection points in wood furniture manufacturing, stone processing and special equipment manufacturing enterprises, and 101, 27 and 78 out of standard points respectively, and the exceeding standard rates were 65.6% (101/154) , 61.4% (27/44) and 69.0% (78/113) , respectively. There were 1670, 172 and 856 workers exposed to noise in the three industries. Among them, 1198, 134 and 703 people had taken occupational health examination. The physical examination rates were 71.7% (1198/1670) , 77.9% (134/172) and 82.1% (703/856) , respectively. The abnormal rates were 19.1% (229/1198) , 51.5% (69/134) and 37.8% (266/703) , respectively.Conclusion:High intensity noise working environment, too long noise exposure time, incorrect wearing of personal protective equipment and neglect of occupational health examination are important reasons for hearing loss of noise exposed personnel.

Objective:To understand the basic situation of noise hazards in wood furniture manufacturing, stone processing and special equipment manufacturing industries in Shenzhen City, and to provide basis for preventing and controlling noise hazards.Methods:In August 2019, stratified random sampling ws used to select 21 wood funiture manafacturing, 15 stone processing and 24 special equipment manufactruing as survey object. Through the methods of occupational health field investigation, noise intensity measurement and occupational health examination data collection, the noise hazards of 60 enterprises in three industries were statistically analyzed.Results:There were 154, 44 and 113 noise detection points in wood furniture manufacturing, stone processing and special equipment manufacturing enterprises, and 101, 27 and 78 out of standard points respectively, and the exceeding standard rates were 65.6% (101/154) , 61.4% (27/44) and 69.0% (78/113) , respectively. There were 1670, 172 and 856 workers exposed to noise in the three industries. Among them, 1198, 134 and 703 people had taken occupational health examination. The physical examination rates were 71.7% (1198/1670) , 77.9% (134/172) and 82.1% (703/856) , respectively. The abnormal rates were 19.1% (229/1198) , 51.5% (69/134) and 37.8% (266/703) , respectively.Conclusion:High intensity noise working environment, too long noise exposure time, incorrect wearing of personal protective equipment and neglect of occupational health examination are important reasons for hearing loss of noise exposed personnel.

Objective: To study the changes of monocyte cytokines in peripheral blood of n-hexane neuropathy patients induced by P₀ protein, and to explore the role of autoimmunity in n-hexane neuropathy patients. Methods: In May 2018, 5 patients with peripheral neuropathy diagnosed as n-hexane poisoning were selected as case group in Shenzhen Prevention and Treatment Center for Occupational Disease in 2017. 6 workers exposure to n-hexane and 6 workers without n-hexane exposure were selected as contact group and control group. Peripheral blood mononuclear cells(PBMC) were isolated from venous blood. Results: The number of spots produced by INF-γ and IL-10 increased after stimulation with P₀ protein in case group, and the positive rate was significantly higher than control group and the contact group. Conclusion Autoimmunity induced by P₀ protein may be involved in the occurrence of myelin sheath damage in n-hexane neuropathy patients.

BACKGROUNDVulvodynia, or vulvar pain, is a common condition in women; however, there are few evidence-based clinical trials evaluating nonpharmacological therapies for this condition. Acupuncture is one complementary and integrative medicine therapy used by some patients with vulvodynia. This study evaluates two different acupuncture strategies for the treatment of vulvodynia and aims to evaluate whether either of the acupuncture protocols reduces vulvar pain, pain duration or pain with intercourse. The study also examines how long the effect of acupuncture lasts in women with vulvodynia.

METHODS/DESIGNThe study is designed as a randomized controlled trial, focused on two acupuncture protocols. Fifty-one patients who have had vulvodynia for more than 3 months will be recruited. Among them, 34 patients will be randomized into Groups 1a and 1b; those who are unwilling to receive acupuncture will be recruited into the standard care group (Group 2). Patients in Group 1a will have acupuncture focused on the points in the pudendal nerve distribution area, while patients in Group 1b will receive acupuncture focused on traditional (distal) meridian points. Patients in Group 2 will receive routine conventional treatments, such as using pain medications, local injections and physical therapies or other nonsurgical procedures. Acupuncture will last 45 min per session, once or twice a week for 6 weeks. The primary outcome measurement will be objective pain intensity, using the cotton swab test. The secondary outcome measurement will be subjective patient self-reported pain intensity, which will be conducted before cotton swab test. Pain intensities will be measured by an 11-point Numeric Pain Rating Scale. Pain duration and pain score during intercourse are recorded. Local muscle tension, tenderness and trigger points (Ashi points) are also recorded. All measurements will be recorded at baseline (before the treatment), at the end of each week during treatment and at the end of the 6 weeks. Follow-up will be done 6 weeks following the last treatment.

DISCUSSIONResults of this trial will provide preliminary data on whether acupuncture provides better outcomes than nonacupuncture treatments, i.e., standard care, and whether acupuncture focused on the points in pudendal nerve distribution, near the pain area, has better results than traditional acupuncture focused on distal meridian points for vulvodynia.

TRIAL REGISTRATIONClinicaltrials.gov: NCT03481621. Register: March 29, 2018.

Objective The aim of this experiment was to explore the effect and mechanism of intestinal microbiota on shaping the growth performance by fecal microbiota transplantation from pigs to pseudo-germ-free mice. Methods Thirty-six barrows with a similar initial body weight of 30 kg were raised for 42 days(ad libitum)within individual metabolic cages. Feed intake and body weight of each pig were recorded every week to calculate the feed conversion rate and average daily gain. At the end of the experiment,feed conversion ratio and average daily gain were integrated to divide the pigs into 3 groups, namely, high growth performance(HP), moderate growth performance(MP)and low growth performance(LP)groups. Feces were collected to calculate the total intestinal nutrient digestibility and prepare for fecal microbiota transplantation to pseudo-germ-free mice, which were induced with several antibiotics for four weeks. Fecal microbiome structure was assayed by profiling V3-V4 region of the 16S rRNA gene. Results Fecal microbiota transplantation from pigs to pseudo-germ-free mice resulted in reappearance of the original phenotype. Compared with the LP pigs, the microbial species richness and microbial diversity in feces were higher in the HP pigs. The HP pigs had improved digestibility of gross energy(P =0.01)and higher abundance of Methanobrevibacter. Enterococcus and Akkermansia were also more abundant in the recipient pseudo-germ-free mice from the HP pigs which may be correlated with a high energy utilization. Conclusions Fecal microbiota transplantation from pigs to mice results in reappearance of the original phenotype and microbial species richness,microbial diversity,and their growth ability. Different nutritional metabolism is shown among pigs with different feed efficiency and the HP pigs have improved energy utilization(P=0.01). At the same time, the bacteria correlated with high energy utilization are more abundant in feces of HP pigs than in LP pigs.