OBJECTIVE: To investigate the impact of early antimicrobial therapy on the prognosis of patients with suspected sepsis in emergency and outpatient settings. METHODS: A prospective cohort study was conducted. Patients with suspected sepsis admitted to the emergency department of Taizhou Hospital, Zhejiang Province, from May 1, 2022, to July 31, 2023, were enrolled. Participants were divided into an early group (0-1 hour) and a delayed group (> 1 hour) according to duration from admission to antimicrobial administration. General information, initial vital signs, laboratory parameters within 24 hours after admission, disease severity scores, vasoactive drug usage, and clinical outcomes of the patient were collected. Kaplan-Meier survival curve was used to analyze 28-day survival. Multivariate Cox proportional hazards regression was performed to identify independent risk factors for prognosis of the patients with suspected sepsis in emergency and outpatient settings. Sensitivity analyses were conducted through subgroup analyses. RESULTS: A total of 143 patients with suspected sepsis were enrolled in the analysis, with 66 patients in the early group and 77 in the delayed group. No statistically significant differences were observed in baseline characteristics (age, gender, vital signs, laboratory parameters, disease severity scores) or clinical outcomes [vasoactive drug usage rate, mechanical ventilation duration, length of intensive care unit (ICU) stay, total hospitalization duration] between the two groups. The 28-day mortality, multidrug resistance rate and sepsis confirmation rate did not differ significantly between the early group and delay group [28-day mortality: 18.2% (12/66) vs. 20.8% (16/77), multidrug resistance rate: 3.0% (2/66) vs. 2.6% (2/77), sepsis confirmation rate: 87.9% (58/66) vs. 88.3% (68/77), all P > 0.05]. Kaplan-Meier survival curve analysis showed no difference in 28-day cumulative survival between the two groups (Log-Rank test: χ² = 2.528, P = 0.112). Multivariate Cox proportional hazards regression identified vasoactive drug usage [hazard ration (HR) = 2.465, 95% confidence interval (95%CI) was 1.019-5.961, P = 0.045] and endotracheal intubation (HR = 5.516, 95%CI was 2.195-13.858, P < 0.001) as independent risk factors for 28-day death of the patients with suspected sepsis in emergency and outpatient settings. Further exploration of the impact of early antimicrobial therapy on 28-day death in different subgroups of the patients with suspected sepsis in emergency and outpatient settings was conducted through subgroup analysis. The results showed that in the patients with different ages (< 60 years old: HR = 1.214, 95%CI was 0.535-2.751, P = 0.643; ≥ 60 years old: HR = 2.085, 95%CI was 0.233-18.668, P = 0.511), sequential organ failure assessment (SOFA) scores (< 6: HR = 1.411, 95%CI was 0.482-4.128, P = 0.530; ≥ 6: HR = 0.869, 95%CI was 0.292-2.587, P = 0.801), shock indexes (< 1: HR = 1.095, 95%CI was 0.390-3.077, P = 0.863; ≥ 1: HR = 1.364, 95%CI was 0.458-4.059, P = 0.577) and whether diagnosed with sepsis or not (yes: HR = 0.943, 95%CI was 0.059-15.091, P = 0.967; no: HR = 1.207, 95%CI was 0.554-2.628, P = 0.636) subgroups, early usage of antibiotics had not shown any advantage in improving prognosis compared with delayed usage. CONCLUSION Early antimicrobial therapy does not improve the prognosis of patients with suspected sepsis in emergency and outpatient settings.
Humans ; Sepsis/drug therapy* ; Prospective Studies ; Prognosis ; Emergency Service, Hospital ; Outpatients ; Female ; Male ; Anti-Infective Agents/therapeutic use* ; Middle Aged ; Aged ; Proportional Hazards Models ; Treatment Outcome

OBJECTIVE To establish the quality standard of Triadica cochinchinensis and to perform the acute toxicity study. METHODS Appearance properties, powder microscopic identification, and thin-layer chromatography(TLC) identification were researched. The specific chromatogram was established by HPLC. The content of cadmium(Cd), lead(Pb), arsenic(As), copper(Cu), and mercury(Hg) was determined by inductively coupled plasma-mass spectrometry(ICP-MS). Acute toxicity was studied by maximum dose. RESULTS The outer skin of herbs was dark brown, and the inner surface was light yellow brown and fibrous. Besides, crystal sheath fiber was common, and calcium oxalate clusters arranges in rows. In the TLC diagram of the test product, the fluorescent spots of the same color were displayed at the corresponding position of the control product(scopoletin, isofraxidin). Five common peaks were calibrated in the characteristic map and the three characteristic peaks(scopoletin, isofraxidin, dimethylfraxetin) were recognized. The content of the measured heavy metal elements was lower than the national limit standard. The linear correlation coefficient was R2 > 0.999. The precision, stability, repetitive RSD were < 10%. The average recovery rate of the added sample was 80%−120%, and the RSD was < 10%. The maximum dose of the acute toxicity test was 184.09 g·kg−1. The 14 d internal body mass, food intake, organ-body ratios, the serum glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, blood urea nitrogen, and creatinine were not significantly different by comparing with the normal controls. Therefore, no significant toxicity was observed. CONCLUSION The established standard can provide a reference for evaluating the quality of Triadica cochinchinensis. The heavy metal content of ten batches of medicinal materials is within the safe range. Acute toxicity test show that there is no obvious significant adverse teactions after oral administration, and the safe dose range is large, which can provide a reference for the subsequent development and utilization.

Objective To establish the reference interval of serum non-high-density lipoprotein cholesterol(n-HDL-C)in adults in Yan'an city of Shaanxi Province and analyze the influencing factors.Methods A total of 16 921 adults from 10 towns in Yan'an City of Shaanxi Province from January to September 2023 were selected by random sampling.Age,sex,smoking,drinking,exercise,hypertension,diabetes,dyslipidemia,chronic disease,residence,eating habits,marital status,education and monthly income were investigated.Height,weight,waist circumference and blood pressure were measured.Serum triglyceride(TG),total cholesterol(TCHO),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),Apolipoprotein A1(ApoA1),Apolipoprotein B(ApoB)and lipoprotein a[Lp(a)]levels were detected,and n-HDL-C levels were calculated:n-HDL-C(mmol/L)=TCHO(mmol/L)-HDL-C(mmol/L).The 95％reference interval(P25～P97 5)was calculated according to the percentile method recommended in WS/T402-2012 Health Industry Standard of the People's Republic of China.Multivariate logistic regression was used to analyze the influencing factors of serum n-HDL-C level.Results The serum n-HDL-C levels in both males and females were not normally distributed(S=2.119,2.091,all P＜0.001).There were significant differences in serum levels of n-HDL-C among males aged＞60 years old[2.98(2.50,3.37)mmol/L],18～30 years old[2.84(2.49,3.26)mmol/L],31～40 years old[2.98(2.62,3.42)mmol/L],41～50 years old[3.10(2.62,3.47)mmol/L]and 51～60 years old[3.05(2.64,3.46)mmol/L]contrast,and the differences were significant(H=3.618～5.680,all P＜0.05).There were significant differences in serum levels of n-HDL-C among women aged 51～60 years[3.08(2.71,3.44)mmol/L],18～30 years[2.64(2.29,3.07)mmol/L],31～40 years[2.67(2.31,3.08)mmol/L]and 41～50 years old[2.94(2.58,3.29)mmol/L]contrast(H=8.161～13.445,all P＜0.001).There were significant differences in serum n-HDL-C levels among patients aged＞60 years old[2.98(2.57,3.34)mmol/L],18～30 years old,31～40 years old and 41～50 years old contrast,and the differences were significant(H=7.985～14.018,all P＜0.001).The reference interval of serum n-HDL-C level in adult population was obtained by combining the age groups with no statistical significance:males aged 18～60 years old(1.97～3.97mmol/L),＞60 years old(1.86～3.91mmol/L);females aged 18～50 years(1.82～3.74 mmol/L),＞50 years old(1.94～3.88 mmol/L).A total of 16 921 adults were divided into normal n-HDL-C group and abnormal group,and the differences of serum TG(1.02±0.31 mmol/L vs 1.24±0.37mmol/L),TCHO(3.97±1.02 mmol/L vs 4.66±1.25 mmol/L),LDL-C(2.37±0.58mmol/L vs 2.59±0.67 mmol/L)levels and age(43.55±11.52 years vs 46.27±8.13 years)between the two groups were significant(t=2.041～3.151,all P＜0.05),in which the abnormal rate of serum n-HDL-C level was 42.50％.Multivariate Logistic regression analysis showed that males,lack of exercise,overweight or obesity,dyslipidemia,urban residents,and high school education or above were the influential factors for serum n-HDL-C levels in adults in this region(all P＜0.05).Conclusion The reference interval of serum n-HDL-C level in adults in this area was preliminarily established.Males,lack of exercise,overweight or obesity,dyslipidemia,urban residents,and high school education or above were the influential factors of abnormal serum n-HDL-C levels in adults in this area.

Gestational diabetes mellitus (GDM) is a serious threat to maternal and infant health. However, the unclear etiology and pathogenesis of GDM is the harrier of clinical intervention. In recent years, the relationship between inflammation and GDM has been widely concerned, but the conclusions are inconsistent. This paper summarizes the research progress on the association between inflammation-related indicators and GDM, in order to provide a basis for the diagnosis, treatment, or prophylaxis of GDM.

Acute pancreatitis (AP) is a devastating disease characterized by an inflammatory disorder of the pancreas. P-selectin glycoprotein ligand-1 (PSGL-1) plays a crucial role in the initial steps of the adhesive at process to inflammatory sites, blockade of PSGL-1 might confer potent anti-inflammatory effects. In this study, we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1, RH001-6 and RH001-22, which were screened from immunized rhesus macaques. We found that RH001-6, can effectively block the binding of P-selectin to PSGL-1, and abolish the adhesion of leukocytes to endothelial cells in vitro. In vivo, we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and l-arginine induced AP models. We also evaluated the safety profile after RH001-6 treatment in mice, and verified that RH001-6 did not cause any significant pathological damages in vivo. Taken together, we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity, named RH001-6, which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP. Therefore, RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases, such as AP.

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

Objective To investigate the current situation of animal injury among children in Chongqing, and to provide a scientific basis for relevant departments to formulate and implement strategies and measures to prevent and control animal injury to children. Methods According to the method of multi-stage stratified cluster sampling, 14,056 children in grades 4-12 in four districts of Chongqing were selected as the investigation subjects, and the occurrence of animal injuries in the past 6 months was investigated. Results The incidence of animal injury among school children in Chongqing was 0.35% and the incidence of person-time was 0.36%. The incidence rate in males (0.48%) was higher than that in females (0.31%). The incidence rate in urban children (0.43%) was higher than that in rural children (0.30%). The incidence of animal injury was the lowest in nuclear families (0.25%), and the highest in single-parent families (0.82%). There were statistically significant differences in the incidence of animal injuries in children among different fathers' occupational types, family types and parents' parenting styles (P<0.05).  The main place of child animal injury was home (57.14%). Recreational activities were the main cause of animal injury (51.02%). The main injuries were lower limbs (42.86%), upper limbs (24.49%) and head (10.20%). Conclusion The prevention and control of children's animal injury in Chongqing should focus on boys and families. It is suggested to take targeted and comprehensive interventions to prevent animal injuries in children.

Objective:To analyze the clinical characteristics and pathogen distributions of the patients with bone and joint infection.Methods:The clinical data and etiological results of 225 patients with bone and joint infection from January 2008 to October 2020 in Huashan Hospital, Fudan University were retrospectively analyzed.Statistical analysis was conducted by chi-square test.Results:Of the 225 cases with bone and joint infection, 75.6%(170/225) were extremities and other osteomyelitis, 16.0%(36/225) were suppurative arthritis, 8.4%(19/225) were spinal osteomyelitis. Non-implants related infection accounted for 80.4%(181/225) of the cases, while 19.6%(44/225) of the cases were implants related infection. The main clinical manifestations were localized pain (48.4%(109/225)), dyskinesia (47.6%(107/225)), localized swelling (28.9%(65/225)), fever (28.0%(63/225)), and increased purulent exudation (24.9%(56/225)). The proportions of localized pain (55.8%(101/181)) and fever (31.5%(57/181)) of non-implants infection were higher than those of implants infection (18.2%(8/44) and 13.6%(6/44), respectively), while the proportion of increased purulent exudation in implants infection (50.0%(22/44)) was higher than that in non-implants infection (18.8%(34/181)). There were all significant differences between the two groups ( χ2=15.49, 5.60 and 18.45, respectively, all P<0.050). Of the 225 cases, 63 cases(28.0%) had complications with other site infection, especially soft tissue infection and bloodstream infection. A total of 106 strains of pathogens were isolated from 225 specimens, 58.5%(62/106) of them were Gram positive bacterium.Among them, 34.0%(36/106) were Staphylococcus aureus, with the rate of methicillin resistant Staphylococcus aureus (MRSA) isolation accounting for 11.3%(12/106). Laboratory tests showed that 40.4%(91/225) of the patients had elevated erythrocyte sedimentation rate (ESR), 32.9%(74/225) patients had elevated C-reactive protein (CRP). Proportions of patients with elevated ESR (43.6%(79/181)) and CRP (37.6%(68/181)) in non-implants infection were significantly higher than those in implants infection (27.3%(12/44) and 13.6%(6/44), respectively). There were significant differences between the two groups ( χ2=3.94 and 9.19, respectively, P=0.047 and 0.002, respectively). Conclusions:The main clinical manifestations of bone and joint infection are localized pain, dyskinesia, localized swelling, fever and increased purulent exudation. Patients with bone and joint infection are easy to be complicated with soft tissue infection and bloodstream infection, and often accompanied by increased ESR and CRP levels. Gram positive bacterium are the main pathogens.

Objective:To optimize the stimulation and activation system of mouse CD3 + T cells in vitro and explore the optimal infection time of CD3 + T cells to establish mouse CD19 chimeric antigen receptor T cells (mCD19 CAR-T) , and to also verify its killing effect in vivo and in vitro. Method:Splenic CD3 +T cells were isolated and purified using magnetic beads, and the cells were cultured in Soluble anti-CD3/CD28, PMA+Ionomycin, and Plated anti-CD3/CD28. Cell activation and apoptosis were assessed by flow cytometry after 8, 24, 48, and 72 hours. ScFv plasmid of mouse CD19 antibody was transfected to plat-E cells to package retrovirus. Activated CD3 + T cells were infected to construct mouse-specific CD19 chimeric antigen receptor T cells (mCD19 CAR-T) , and mCD19 CAR-T cells were co-cultured with B-cell lymphoma cell line A20 in vitro. The specific toxicity of A20 was detected by flow cytometry, and mCD19 CAR-T cells were infused into the lymphoma mouse model to detect its killing effect and distribution. Results:The activation effect of Plated anti-CD3/CD28 on CD3 + T cells was superior, with the cells exhibiting good viability 24–48 hours after stimulation. Established mCD19 CAR-T cells with stable efficiency[ (32.27±7.56) % ] were specifically able to kill A20 tumor cells (The apoptosis rate was 24.3% at 48 h) . In vivo detection showed a non-significant decrease in the percentage[ (1.83±0.58) % ] of splenic CD19 + cells 6 days after mCD19 CAR-T cell infusion. A marked clearance in bone marrow and spleen appeared on day 12 compared with the A20 group, and this difference was statistically significant[spleen: (0.36±0.04) % vs (47.00±13.46) % , P<0.001; bone marrow: (1.82±0.29) % vs (37.30±1.44) % , P<0.0001]. Moreover, mCD19 CAR-T cells were distributed in high proportions in the peripheral blood, spleen, and bone marrow[ (2.90±1.12) % , (4.96±0.80) % , (13.55±1.56) % ]. Conclusion:This study demonstrated an optimized activation system and the optimal infection time of CD3 + T cells. Furthermore, stable constructed mCD19 CAR-T cells showed a remarkable killing ability in vitro and in vivo.