Objective To analyze the influencing factors for the knowledge level,cognition willingness and atti-tude of health care workers(HCWs)towards monkeypox.Methods A cross-sectional survey was conducted,from January to April 2023,700 HCWs were randomly selected from a tertiary hospital in Shanghai.Based on a self-de-signed questionnaire,the survey was conducted anonymously through the online platform"Wenjuanxing".Results A total of 612 questionnaires were collected,581 were valid,with a response rate of 87.43％and an effective rate of 94.93％.The mean score of the questionnaire was(128.80±27.70)points,with a score rate of 58.54％.Multiple linear regression analysis showed that there were statistically significant differences in the knowledge level of mon-keypox among HCWs of different ages,occupations,departments,educational levels,years of working experience,professional titles,initiative cognition on monkeypox,and participation in monkeypox-related lectures organized by the units(all P＜0.05).Conclusion HCWs'cognition on monkeypox is at a moderate level.The training of HC-Ws on monkeypox knowledge should be strengthened to improve the emergency response capabilities during mon-keypox outbreaks.

Aim To investigate the enhanced efficacy and reduced toxicity of GanoExtra in combination with cyclophosphamide(CTX)on inhibiting lung metastasis and immune function in mice.Methods The CCK-8 method was used to verify the cytotoxic effects of Gano-Extra on MCF-7 and 4T1 tumor cells.In vivo experi-ment,a mouse model of lung metastasis of breast canc-er was established by injecting 4T1 tumor cells into the tail vein,which was divided into four groups including 4T1 model group,CTX group,GanoExtra group and GanoExtra+CTX group.The control group was set.After 21 days,the mice were euthanized under anes-thesia,and the body weight of the mice was recorded.Average lung index and spleen index were calculated.The mouse spleen lymphocyte transformation experi-ment was used to determine the activity of spleen cells.The NK cell activity assay was used to determine the activity of NK cells.Blood cells were determined in mouse blood samples.Flow cytometry was used to de-termine the levels of CD4+and CD8+T cells in blood samples.ELISA was used to measure the levels of TNF-α and IL-6 in serum.HE staining was used to ob-serve the pathological morphological changes in tumors and various tissues;and CFSE staining was used to de-termine the proliferative effect of GanoExtra on CD8+cells.Results In vitro GanoExtra at 50 mg·L-1 sig-nificantly inhibited the activity of MCF-7 and 4T1 tumor cells.In the breast cancer pulmonary metastasis model,compared with the model group,the spleen in-dex and blood WBCs content were significantly re-duced,while the activity of NK cells,spleen cells,and the proportion of RBCs,CD 3+and CD 8+T cells in the blood were significantly increased.At the end of the treatment,compared with the CTX group,the number of lung metastases and lung index of the Gano-Extra+CTX group were significantly reduced,and the levels of HGB,CD8+cells,IL-6,and TNF-α in the blood of mice were significantly increased.GanoExtra at 10 mg·L-1 significantly promoted the proliferation of CD8+T cells in vitro.Conclusions GanoExtra can enhance the inhibitory effect of CTX on tumor metasta-sis,alleviate adverse reactions such as splenomegaly and pulmonary enlargement caused by CTX,and have a health-promoting function of promoting the prolifera-tion of CD8+T cells to enhance the immune efficacy of the body.

Attenuated Salmonella typhimurium VNP20009 is a widely used natural oncolytic bacterium, which has great application potential given its unique characteristics, including clinical safety, tumor targeting specificity, and explicit genome sequence. Here, we show that tumor progression can be effectively reduced by intraperitoneal administration with VNP20009 in a mouse model of melanoma (all animal experiments were conducted in accordance with the Animal Ethics Committee of China Pharmaceutical University); co-culture experiment in vitro demonstrated that VNP20009 can induce the polarization of macrophage M1, accompanied by expression of inflammation-related factors; flow cytometry analysis showed that VNP20009 induced the increase of immune cell infiltration in tumor. Further analysis showed that T cells infiltration in tumor-draining lymph node (TDLN) increased, and VNP20009 induced the activation of CD4⁺ T cells and CD8⁺ T cells in tumor. Our results demonstrate that VNP20009 treatment significantly inhibited melanoma tumors by remodeling tumor-associated macrophages to an M1-like phenotype, as well as recruiting and activating cytotoxic T cells, combined with its own antigenic activity to exert anti-tumor immunity.

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

This study aims to study the effective substance and mechanism of Ziziphi Spinosae Semen extract in the treatment of insomnia based on serum metabolomics and network pharmacology. The rat insomnia model induced by p-chlorophenylalanine(PCPA) was established. After oral administration of Ziziphi Spinosae Semen extract, the general morphological observation, pentobarbital sodium-induced sleep test, and histopathological evaluation were carried out. The potential biomarkers of the extract in the treatment of insomnia were screened by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS) combined with multivariate analysis, and the related metabolic pathways were further analyzed. The "component-target-pathway" network was constructed by ultra-high performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry(UHPLC-Q-Exactive-MS/MS) combined with network pharmacology to explore the effective substances and mechanism of Ziziphi Spinosae Semen in the treatment of insomnia. The results of pentobarbital sodium-induced sleep test and histopathological evaluation(hematoxylin and eosin staining) showed that Ziziphi Spinosae Semen extract had good theraputic effect on insomnia. A total of 21 endogenous biomarkers of Ziziphi Spinosae Semen extract in the treatment of insomnia were screened out by serum metabolomics, and the metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and nicotinate and nicotinamide metabolism were obtained. A total of 34 chemical constituents were identified by UHPLC-Q-Exactive-MS/MS, including 24 flavonoids, 2 triterpenoid saponins, 4 alkaloids, 2 triterpenoid acids, and 2 fatty acids. The network pharmacological analysis showed that Ziziphi Spinosae Semen mainly acted on target proteins such as dopamine D2 receptor(DRD2), 5-hydroxytryptamine receptor 1 A(HTR1 A), and alpha-2 A adrenergic receptor(ADRA2 A) in the treatment of insomnia. It was closely related to neuroactive ligand-receptor interaction, serotonergic synapse, and calcium signaling pathway. Magnoflorine, N-nornuciferine, caaverine, oleic acid, palmitic acid, coclaurine, betulinic acid, and ceanothic acid in Ziziphi Spinosae Semen may be potential effective compounds in the treatment of insomnia. This study revealed that Ziziphi Spinosae Semen extract treated insomnia through multiple metabolic pathways and the overall correction of metabolic disorder profile in a multi-component, multi-target, and multi-channel manner. Briefly, this study lays a foundation for further research on the mechanism of Ziziphi Spinosae Semen in treating insomnia and provides support for the development of innovative Chinese drugs for the treatment of insomnia.
Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Metabolomics ; Network Pharmacology ; Rats ; Seeds/chemistry* ; Sleep Initiation and Maintenance Disorders/drug therapy* ; Tandem Mass Spectrometry ; Ziziphus/chemistry*

Objective: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) in the treatment of autism spectrum disorder (ASD). Methods: A longitudinal study was conducted. Clinical data from ASD patients with gastrointestinal symptoms and who underwent FMT in the Tenth People's Hospital affiliated to Tongji University or Jinling Hospital between May 2012 to May 2021 were retrospectively collected. Scores derived from the autism behavior checklist (ABC), the childhood autism rating scale (CARS), the Bristol stool form scale (BSFS), and the gastrointestinal symptom rating scale (GSRS) were analyzed at baseline and at the 1st, 3rd, 6th, 12th, 24th, 36th, 48th and 60th month after FMT. Records of any adverse reactions were collected. Generalized estimating equations were used for analysis of data on time points before and after FMT. Results: A total of 328 patients met the inclusion criteria for this study. Their mean age was 6.1±3.4 years old. The cohort included 271 boys and 57 girls. The percentage of patients remaining in the study for post-treatment follow-up at the 1st, 3rd, 12th, 24th, 36th, 48th and 60th month were as follows: 303 (92.4%), 284 (86.7%), 213 (64.9%), 190 (57.9%), 143 (43.6%), 79 (24.1%), 46 (14.0%), 31 (9.5%). After FMT, the average ABC score was significantly improved in the first 36 months and remained improved at the 48th month. However, the average score was not significantly different from baseline by the 60th month (1st-36th month, P<0.001; 48th month, P=0.008; 60th month, P=0.108). The average CARS score improved significantly during the first 48 months and remained improved at the 60th month (1st-48th month, P<0.001; 60th month, P=0.010). The average BSFS score was also significantly improved in the first 36 months (with an accompanying stool morphology that resembled type 4). This improvement was maintained at the 48th month. However, the average score was similar to baseline at the 60th month (1st-36th month, P<0.001; 48th month, P=0.008; 60th month, P=0.109). The average GSRS score was significantly improved during the first 24 months, but not afterwards (1st-24th month, P<0.001; 36th month, P=0.209; 48th month, P=0.996; 60th month, P=0.668). The adverse events recorded during treatment included abdominal distension in 21 cases (6.4%), nausea in 14 cases (4.3%), vomiting in 9 cases (2.7%), abdominal pain in 15 cases (4.6%), diarrhea in 18 cases (5.5%), fever in 13 cases (4.0%), and excitement in 24 cases (7.3%). All adverse reactions were mild to moderate and improved immediately after suspension of FMT or on treatment of symptoms. No serious adverse reactions occurred. Conclusion: FMT has satisfactory long-term efficacy and safety for the treatment of ASD with gastrointestinal symptoms.
Autism Spectrum Disorder/therapy* ; Child ; Child, Preschool ; Fecal Microbiota Transplantation/adverse effects* ; Feces ; Female ; Gastrointestinal Diseases ; Humans ; Longitudinal Studies ; Male ; Retrospective Studies

Objective: To explore and establish the preparation system of human intestinal fluid transplantation (HIFT) and HIFT capsule, and to preliminarily apply it to clinic. Methods: Strict standards for donor screening and management were established. The nasojejunal tube was catheterized into the distal jejunum, and then it was connected with an improved disposable sterile negative pressure collection device for the collection of human intestinal fluid. After that, it was prepared into capsules by filtering, adding 10% glycerin protectant and freeze-drying method. The amount of living bacteria was used as the standard of therapeutic dose. The living bacteria amount in fluid is ≥ 5.0×10⁸ /mL and the living bacteria proportion is ≥ 83%; the living bacteria amount in powder is ≥ 2.0×10⁶ /g and the living bacteria proportion is ≥ 81%; The observational indicators included: (1) the basic information of the donor, the amount of living bacteria in the HIF and powder. (2) Preliminary analysis of the treatment for ASD, which combined HIFT capsule with standard FMT capsule, from February to December 2021 (Clinical trial Registration Number: ChiCTR2100043929). Evaluation criteria: Trypan blue staining method was used to detect the living bacteria amount in fluid and powder. The Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS) were used to evaluate the efficacy. Results: Compared with the parent donor, the standard donor was younger [(25.4±0.9) y vs. (30.7±3.2) y, t=-19.097, P=0.001] and had a lower body mass index [(19.7±0.5) kg/m² vs. (20.8±1.3) kg/m², t=-8.726, P=0.001], more in the living bacteria amount in powder [(7.47±1.52)×10⁶/g vs. (5.03±1.38)×10⁶/g, t=11.331, P=0.031], Chao index (205.4±6.8 vs. 194.2±7.2, t=10.415, P=0.001), and Shannon index (3.25±0.14 vs 2.72±0.27, t=19.465, P=0.001). The differences were statistically significant (all P<0.05). However, there were no significant differences in gender, drainage volume and total number of bacterial liquid colonies between the two groups (all P>0.05). Both the standard donor and the parent donor met the donor screening criteria, and the preparation fluid and powder met the treatment criteria. Eight patients received the treatment of HIFT combined with fecal microbiota transplantation (FMT). Preliminary statistical results showed that HIFT combined with FMT improved ABC and CARS at the 1st, 2nd, 3rd and 4th months. The differences were statistically significant (all P<0.05). No severe adverse reaction occurred. Conclusion: Based on the previous research on FMT preparation system and the clinical technology in our center, this study developed a high standard HIFT preparation system, and explored the clinical study of HIFT combined with FMT, in order to provide an innovative therapy for the treatment of diseases.
Bacteria ; Child ; Fecal Microbiota Transplantation/methods* ; Glycerol ; Humans ; Powders ; Trypan Blue

As a dangerous disease with rapid progression, endotoxemia is easy to induce the damage to multiple organs. However, its specific and efficient treatment methods are still lacking at present. Both Qingkailing Injection(QKLI) and Shengmai Injection(SMI) have been proved effective in anti-inflammation, anti-endotoxin and organ protection. In this study, carrageenan and endotoxin were injected successively into rats to establish an endotoxemia model. Different doses of QKLI and SMI were administered to the endotoxemia rats by intraperitoneal injection separately or in combination. Then the count of white blood cells, the number of platelets, the content of cytokines, biochemical indexes, organ coefficient and pathological changes of main organs in the rats were detected. The results showed that the rats in the model group had obvious symptoms of endotoxemia, i.e., leucopenia, thrombocytopenia, increase in cytokines(IL-6 and TNF-α) and biochemical indexes of liver and kidney function as well as pathological damage to liver, kidney and lung. QKLI alone can alleviate the above symptoms of endotoxemia and the organ injury. SMI alone is less effective in improving disseminated intravascular coagulation(DIC) and cytokine secretion complicated with endotoxemia, but capable of reducing the inflammation degree of the lung, liver and kidney. The combination of QKLI and SMI remarkably increased the number of platelets in the peripheral blood, improved the liver and kidney function and reduced inflammatory factors, with lung, liver, kidney and other organ structures protected well. Moreover, the improvement effect of the combination of QKLI and SMI was stronger than those of the two injections alone at fixed doses, indicative of a synergistic effect.
Animals ; Drug Combinations ; Drugs, Chinese Herbal ; Endotoxemia/drug therapy* ; Rats

Purpose: Systemic inflammatory response is a critical factor that promotes the initiation and metastasis of malignancies including pancreatic cancer (PC). This study was designed to determine and compare the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and fibrinogen-to-albumin ratio (FAR) in resectable PC and locally advanced or metastatic PC. Materials and Methods: Three hundred fifty-three patients with resectable PC and 807 patients with locally advan-ced or metastatic PC were recruited in this study. These patients were classified into a training set (n=758) and a validation set (n=402). Kaplan-Meier survival plots and Cox proportional hazards regression models were used to analyze prognosis. Results: Overall survival (OS) was significantly better for patients with resectable PC with low preoperative PLR (p=0.048) and MLR (p=0.027). Low FAR, MLR, NLR (p < 0.001), and PLR (p=0.003) were significantly associated with decreased risk of death for locally advanced or metastatic PC patients. FAR (hazard ratio [HR], 1.522; 95% confidential interval [CI], 1.261 to 1.837; p < 0.001) and MLR (HR, 1.248; 95% CI, 1.017 to 1.532; p=0.034) were independent prognostic factors for locally advanced or metastatic PC. Conclusion The prognostic roles of FAR, MLR, NLR, and PLR in resectable PC and locally advanced or metastatic PC were different. FAR showed the most prognostic power in locally advanced or metastatic PC. Low FAR was positively correlated with OS in locally advanced or metastatic PC, which could be used to predict the prognosis.