OBJECTIVE To explore the mechanism of Shaoyao gancao decoction in improving intestinal motility in rats with slow transit constipation （STC） by regulating acid-sensitive ion channel 3 （ASIC3）/extracellular signal-regulated kinase （ERK） signaling pathway. METHODS SD rats were used to construct an STC model by gavage with compound diphenoxylate. The successfully modeled rats were randomly divided into model group， Shaoyao gancao decoction group （1.5 g/mL）， lactulose group （208.4 mg/mL， positive control）， and combined inhibition group （Shaoyao gancao decoction 1.5 g/mL+amiloride hydrochloride 20 μg/kg）， with 12 rats in each group. Additionally， 12 healthy rats were selected as the blank group. They were given relevant medicine once a day and continuously intervened for 14 days. After intervention， the intestinal propulsion function and visceral sensitivity of the model rats were detected. The expression of ASIC3 in the colon tissue of rats was observed by immunohistochemical staining. mRNA expressions of ASIC3， ERK1 and ERK2 as well as protein expressions of ASIC3， ERK1/2 and phosphorylated ERK1/2 （p-ERK1/2） in colon tissue of rats were detected； the ultrastructural changes of the enteric nervous system （ENS） -interstitial cell of Cajal （ICC）-smooth muscle cell （SMC） network in the rat colon were observed under electron microscopy. RESULTS Compared with the model group， the intestinal propulsion rate of the Shaoyao gancao decoction group was significantly increased， while the visceral pain threshold was significantly decreased. The proportion of the positive area of ASIC3 in the colonic tissue was significantly increased. The relative mRNA expression levels of ERK1， ERK2， and ASIC3， as well as the relative protein expression levels of p-ERK1/2 and ASIC3， and the p-ERK1/2 to ERK1/2 in the colonic tissue， were all significantly increased （P＜0.05 or P＜0.01）. Additionally， there was marked repair of the morphological structure of ICC and SMC， with closer gap junctions observed. Compared with the Shaoyao gancao decoction group， the combined inhibition group exhibited a diminished improvement in intestinal motility of rats， with statistically significant differences in the levels of some indicators （P＜0.05 or P＜0.01）； the repairing of the morphological structure of ICC and SMC was notably attenuated. CONCLUSIONS Shaoyao gancao decoction can effectively improve the intestinal transmission function and promote intestinal repair in STC rats， and its mechanism may be related to regulating the balance of the ENS-ICC-SMC network mediated by the ASIC3/ERK signaling pathway， thus promoting intestinal motility and reducing visceral sensitivity.

ObjectiveTo explore the mechanism of modified Xiehuangsan in treating tic disorders （TD） based on microglial polarization and the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor （NF）-κB pathway. MethodsSeventy-two Sprague-Dawley （SD） rats were randomly assigned into six groups： control， model， tiapride （0.025 g·kg^-1）， and low-， medium-， and high-dose （12， 24， 48 g·kg^-1， respectively） modified Xiehuangsan， with 12 rats in each group. Except the control group， the other groups received intraperitoneal injection of 3，3'-iminodipropionitrile （IDPN） for 7 consecutive days for the modeling of TD. After successful modeling， the control and model groups were given normal saline via gavage， and the other groups were administrated with corresponding drugs by gavage. After 28 days of continuous intervention， rat behaviors were observed， and the modified Xiehuangsan group showing the best anti-TD effect was selected for deciphering the treatment mechanism. Hematoxylin and eosin staining was conducted to observe morphological changes in the rat striatum. Immunohistochemistry was employed to detect the expression of CD16 and CD206 in the striatum. Real-time PCR was employed to measure the mRNA levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， IL-4， TLR4， MyD88， and NF-κB p65 in the striatum. Western blot was employed to determine the protein levels of ionized calcium-binding adapter molecule 1 （Iba1）， Fc receptor family for immunoglobulin （Ig）G type Ⅲ （CD16）， mannose receptor （CD206）， TLR4， MyD88， and NF-κB p65 in the striatum. ResultsCompared with the control group， the model group showed increased stereotyped behaviors， locomotor activity， total movement distance， and movement speed， shortened resting time （P<0.01）， and noticeable pathological changes in the striatum. Compared with the model group， the tiapride group and modified Xiehuangsan groups exhibited reduced stereotyped behavior， locomotor activity， total movement distance， and movement speed， prolonged resting time （P<0.05， P<0.01）， and alleviated pathological changes in the striatum. Among the modified Xiehuangsan groups， the high-dose group had the best intervention effect and the mildest pathological changes. Therefore， the high-dose group was selected for further research. Compared with the control group， the modeling of TD increased Iba1 and CD16 expression （P<0.05， P<0.01）， up-regulated the mRNA levels of IL-1β and TNF-α （P<0.05， P<0.01）， down-regulated the mRNA level of IL-4 （P<0.05）， up-regulated the mRNA and protein levels of TLR4 and MyD88 （P<0.05， P<0.01）， and up-regulated the protein level of NF-κB p65 （P<0.01）. Compared with the model group， modified Xiehuangsan reduced Iba1 and CD16 expression （P<0.05， P<0.01）， up-regulated the protein level of CD206 （P<0.05， P<0.01）， down-regulated the mRNA levels of IL-1β and TNF-α （P<0.05）， up-regulated the mRNA level of IL-4 （P<0.01）， and down-regulated the mRNA and protein levels of TLR4， MyD88， and NF-κB p65 （P<0.05， P<0.01）. ConclusionModified Xiehuangsan demonstrated a definite therapeutic effect on TD in rats. It may reduce neuroinflammation in TD rats by regulating the polarization of microglia in the striatum via the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveTo investigate the mechanisms by which the combination of berberine （BBR） and baicalin （BAI） ameliorates type 2 diabetes mellitus （T2DM） due to internal accumulation of dampness-heat from the perspectives of gut microbiota and metabolomics. MethodsAntibiotics were used to induce pseudo-sterile mice. Thirty pseudo-sterile mice were randomized into a normal fecal microbiota transplantation group （n=10） and a T2DM （syndrome of internal accumulation of dampness-heat） fecal microbiota transplantation group （n=20）. The mice were then administrated with suspensions of fecal microbiota from healthy volunteers and a patient with T2DM due to internal accumulation of dampness-heat by gavage， respectively. Each mouse received 200 µL suspension every other day for a total of 15 times to reshape the gut microbiota. The T2DM model mice were then assigned into a model group （n=8） and a BBR-BAI group （n=11）. BBR was administrated at a dose of 200 mg·kg^-1， and BAI was administrated in a ratio of BBR-BAI 10∶1 based on preliminary research findings. The administration lasted for 8 consecutive weeks. Fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， insulin （INS）， triglycerides （TG）， total cholesterol （CHOL）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） levels were measured to evaluate the effects of the BBR-BAI combination on glucose and lipid metabolism and liver function in T2DM mice. Hematoxylin-eosin staining was employed to observe pathological changes in the colon tissue. The expression of claudin-1， zonula occludens-1 （ZO-1）， and occludin in the colon tissue was determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to assess the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the colon tissue. The fecal microbiota composition and differential metabolites were analyzed by 16S rRNA sequencing and ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS）， respectively. ResultsThe BBR-BAI combination lowered the FBG， HbA1c， and INS levels （P<0.05， P<0.01） and alleviated insulin resistance （P<0.01） in T2DM mice. Additionally， BBR-BAI elevated the levels of ZO-1， occludin， and claudin-1 （P<0.05， P<0.01） and down-regulated the expression levels of TNF-α， IL-1β， and IL-6 in the colon （P<0.05， P<0.01）. The results of 16S rRNA sequencing showed that BBR-BAI increased the relative abundance of Ligilactobacillus， Phascolarctobacterium， and Akkermansia （P<0.05）， while significantly decreasing the relative abundance of Alistipes， Odoribacter， and Colidextribacter （P<0.05）. UPLC-Q-TOF-MS identified 28 differential metabolites， which were primarily involved in arachidonic acid metabolism and α-linolenic acid metabolism. ConclusionBBR-BAI can ameliorate T2DM due to internal accumulation of dampness-heat by modulating the relative abundance of various bacterial genera in the gut microbiota and the expression of fecal metabolites.

Objective To analyze the epidemiological characteristics of leptospirosis in China from 2010 to 2022, so as to provide insights into formulation of the leptospirosis control strategy. Methods All data pertaining to clinically diagnosed cases and confirmed cases of leptospirosis reported in China from January 1, 2010 to December 31, 2022 was collected from Chinese Disease Prevention and Control Information Management System. The spatial, temporal and population distributions, and report and diagnosis institutions of leptospirosis cases were analyzed using a descriptive epidemiological method. Results A total of 4 559 leptospirosis cases were reported in China from 2010 to 2022, with an annual average number of 351 cases, and the number of reported leptospirosis cases reduced from 679 cases in 2010 to 158 cases in 2018. A total of 4 276 leptospirosis cases were reported in Sichuan Province, Yunnan Province, Guangdong Province, Hunan Province, Fujian Province, Zhejiang Province, Guangxi Zhuang Autonomous Region, Anhui Province, Jiangxi Province and Guizhou Province, accounting for 93.79% of the total number of leptospirosis cases in China. The number of leptospirosis cases had recently appeared a remarkable decline in Yunnan Province, while a significant rise was seen in the number of leptospirosis cases in two provinces of Zhejiang and Guangdong. No leptospirosis cases were reported in Henan Province from 2010 to 2020; however, there were 5 cases and 2 cases reported in 2021 and 2022, respectively. There was only one leptospirosis case reported in Shaanxi Province from 2010 to 2017; however, leptospirosis cases were reported in the province for 5 consecutive years since 2018. Leptospirosis cases were reported throughout the year in China from 2010 to 2022, with the peak of incidence found during the period between August and October, and the peak of leptospirosis incidence varied in provinces. A higher number of leptospirosis cases was seen among men than among women, with a male to female ratio of 2.3:1, and the median age of leptospirosis cases was 50 years (interquartile range, 23 years), with the highest proportion of leptospirosis cases reported at ages of 51 to 60 years (23.21%). Among all reported leptospirosis cases, 53.28% were confirmed cases, and the proportion of confirmed cases increased from 35.05% in 2010 to 61.66% in 2022. In addition, there were 67.22% of leptospirosis cases (2 937 cases) reported by comprehensive hospitals, 20.44% (893 cases) by disease control and prevention institutions, 7.23% (316 cases) by grassroots healthcare institutions and 5.10% (223 cases) by other healthcare and medical institutions, and the mortality of reported leptospirosis cases was 1.07% in China from 2010 to 2022, with a higher mortality seen among men than among women (1.39% vs. 0.36%; χ² = 9.52, P = 0.002). Conclusions The incidence of leptospirosis remained at a low level in China from 2010 to 2022, and southern China was still the main endemic area for leptospirosis. The epidemiological characteristics of leptospirosis cases varied in endemic provinces, and leptospirosis cases had been continued to be reported in Shaanxi and Henan provinces, which should be paid much attention to. Intensified surveillance of leptospirosis, improved diagnosis and treatment capability of leptospirosis cases and leptospirosis control with adaptations to local circumstance are recommended.

Visceral leishmaniasis is a zoonotic parasitic disease caused by viscerotropic Leishmania species and transmitted by bites of infected phlebotomine sandflies, which is predominantly prevalent in the Indian subcontinent, eastern Africa and South America. Currently, visceral leishmaniasis is the second most fatal parasitic disease in the world. Because of climate changes, urban development and individual conditions, there are changes in the density of visceral leishmaniasis vector sandflies and the likelihood of contact with humans, resulting in a visceral leishmaniasis transmission risk. The review summarizes natural, social and biological factors affecting the transmission of visceral leishmaniasis, so as to provide insights into formulation of targeted control measures for visceral leishmaniasis.

Objective: To understand the status quo of school bullying among middle school students in Anhui Province and its correlation with family environment and education methods of students related to school bullying, so as to provide corresponding prevention and controlling measures against school bullying. Methods: The investigation has been conducted on the occurrence of school bullying among middle school students ranging from junior grade one to senior grade three in Hefei, Wuhu, Fuyang of Anhui Province, during which up to 1 826 students information has been gathered through Questionnaire Atar Platform using the school bullying scale and self designed questionnaire. SPSS 26.0 statistical software has been applied for data analysis. Results: The incidence of bullying was 41.40%, and among them, 14.46% were reported to bully others, 39.59% of them were of being bullied, and 12.65% of them were reported of bullying others and being bullied at the same time. Multivariate Logistic regression corrected model showed that quiet relationship with mother ( OR=1.76, 95%CI =1.22-2.53) was a risk factor for the bully, quiet relationship with father( OR=1.89, 95%CI=1.47-2.43 ), reorganized family ( OR=2.28, 95%CI =1.22-4.29) were the risk factors for the bullied, quiet/poor relationship between parents ( OR=1.52, 95%CI=1.06-2.17; OR=3.15, 95%CI =1.79-5.57) was a risk factor for the bully-bullied; Punishment and abuse( OR=1.45, 95%CI=1.10-1.90; OR=1.82, 95%CI=1.48-2.23; OR=1.47, 95%CI = 1.10- 1.96) were risk factors for the above three behaviors( P <0.05). Conclusion The incidence of school bullying is influenced by family environment and rearing style. In daily life, parents should be mindful of maintaining a good family relationship, fostering active communication with child, which can reduce the occurrence of school bullying.

OBJECTIVE: To observe the acute toxic reaction of the Li-Dan-He-Ji granules, and to evaluate its safety. METHODS: Sixty C57BL6/J mice were randomly divided into normal control group, vehicle group and drug treatment group, with 10 females and 10 males in each group. According to the Technical guidelines for the study of toxicity of single drug administration, the maximum administration dosage (MAD) was used to intragastric administration of Li-Dan-He-Ji granules 0.04 mL/g (42.8 g/kg), three times within 24 hours, with an interval of 6 hours. The vehicle group was fed with the same pure water. The normal control group received no treatment. The mice were observed continuously for 14 days, and the appearance characteristics, behavioral activities, body weight changes and the number of deaths in each group were recorded. At the 14 days, blood samples were collected from the eyeballs, and routine blood tests such as white blood cell count (WBC), lymphocyte count (LYM), neutrophil count (NEU), lymphocyte percentage (LYM%), neutrophil percentage (NEU%), red blood cell count (RBC), hemoglobin (Hb), and platelet count (PLT) were performed. And alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine (Cr) and other biochemical indicators. The mice were then sacrificed, and the histopathological changes of liver and kidney were observed by hematoxylin-eosin (HE) staining. The organ indexes of heart, liver, spleen, lung, kidney and thymus were calculated. RESULTS: The median lethal dose (LD₅₀) of Li-Dan-He-Ji granules were not obtained. During the MAD experiment, the animals in each group did not die, their behavioral activities were normal, and there was no significant change in liver and kidney histopathological examination. There were no significant differences in body weight, blood routine, biochemical indexes and organ index among all groups (all P > 0.05). The body weight (g) of normal control female and male group, vehicle female and male group and drug female and male group before administration were 18.96±1.14, 19.65±1.45, 19.33±1.30, 19.53±1.22, 19.28±1.69 and 19.48±1.28; 14 days after administration were 27.69±0.81, 28.19±2.22, 27.77±1.00, 27.88±1.85, 27.92±1.33 and 28.07±1.93, respectively. CONCLUSIONS The Li-Dan-He-Ji granules have low oral toxicity, combined with clinical observation, can be safely used in infants.
Animals ; Female ; Humans ; Male ; Mice ; Body Weight ; Kidney ; Leukocyte Count ; Liver ; Toxicity Tests, Acute

To reduce the burden of researchers, Article 32 of the Measures for Ethical Review of Life Sciences and Medical Research Involving Human issued in February 2023 proposed that the review could be exempted. Normative exemption from review can not only relieve the burden of researchers, but also reduce the work pressure of the ethics committee, and devote limited time and energy to the review and supervision of high-risk research. This paper analyzed the four criteria for exemption from review first, and then summarized the situation of exemption from ethics review in the International Ethical Guidelines for Health-related Research Involving Humans and in the United States. In view of the fact that there are no relevant regulations on exemption from ethics review, though some medical and health institutions have implemented exemption from ethics review for some studies, the ethics committee often lacks standard operating procedures, corresponding documents, and experience for exemption from ethics review, researchers lack training for exemption from ethics review, and institutions have no supporting measures for exemption from review. To effectively implement the exemption from review, this paper proposed the following suggestions:developing standard operating procedures for exemption from review, and clarifying the review process, which can be simplified to secretary reviews, with senior secretaries or office directors judging whether they meet the exemption criteria, and the chairman reviewing and signing to convey the review decision. Refining the criteria that meet the exemption from ethics review, and providing cases and explanations as necessary, which will help researchers accurately understand the connotation of each criterion, and also provide reference for researchers to make their own preliminary judgments. Strengthening the training of researchers’ exemption from review criteria. The study should obtain the project proposal first, and provide scientific demonstration opinions. To explore the implementation of continuing review, institutions should accelerate the standardized construction of biological sample banks and databases to ensure the provision of compliant sources of biological samples and information data. Exemption from ethics review should not be abused, and the relationship between reducing the burden on researchers and ensuring the quality of ethical review should be balanced.

Objective:To explore the association of the impaired cognition and the deposition of β-amyloid (Aβ) in normal cognitive (NC) and mild cognitive impairment (MCI).Methods:From December 2018 to January 2021, 305 subjects (113 males, 192 females; age (64.0±7.7) years) who completed neuropsychological tests and MRI in Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University and 18F-florbetapir (AV45) PET imaging in Huashan Hospital, Fudan University were retrospectively analyzed. The subjects were divided into MCI group and NC group based on neuropsychological tests, and each group was further divided into Aβ-positive and Aβ-negative based on PET imaging results. Independent-sample t test, Mann-Whitney U test and χ2 test were used to analyze the data. Results:There were 118 subjects in MCI group and 187 subjects in NC group. The Aβ-positive rate in MCI group (37.3%, 44/118) was higher than that in NC group (26.2%, 49/187; χ2=4.19, P=0.041). The assessment performances of MCI group in general cognitive function, memory function, language function and executive function were inferior to those of NC group ( t values: from -10.63 to -6.31, z values: from -11.01 to -6.03, all P<0.001). The Auditory Verbal Learning Test-Long Delay Recall (AVLT-LDR) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in MCI group (1.00(0.00, 3.00) and 3.00(1.00, 4.00); z=-2.49, P=0.013). The Montreal Cognitive Assessment Basic (MoCA-B) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in NC group (25.29±2.67 and 26.36±2.42; t=-2.61, P=0.010). Conclusion:Compared to Aβ-negative subjects, MCI patients with Aβ-positive perform worse on memory tests, and NC subjects with Aβ-positive perform worse on general cognitive function.

Multiple myeloma (MM) is still an incurable hematologic malignancy, which is eagerly to the discovery of novel therapeutic targets and methods. N-acetyltransferase 10 (NAT10) is the first reported regulator of mRNA acetylation that is activated in many cancers. However, the function of NAT10 in MM remains unclear. We found significant upregulation of NAT10 in MM patients compared to normal plasma cells, which was also highly correlated with MM poor outcome. Further enforced NAT10 expression promoted MM growth in vitro and in vivo, while knockdown of NAT10 reversed those effects. The correlation analysis of acetylated RNA immunoprecipitation sequencing (acRIP-seq) and ribosome profiling sequencing (Ribo-seq) combined with RIP-PCR tests identified centrosomal protein 170 (CEP170) as an important downstream target of NAT10. Interfering CEP170 expression in NAT10-OE cells attenuated the acceleration of cellular growth caused by elevated NAT10. Moreover, CEP170 overexpression promoted cellular proliferation and chromosomal instability (CIN) in MM. Intriguingly, remodelin, a selective NAT10 inhibitor, suppressed MM cellular growth, induced cellular apoptosis in vitro and prolonged the survival of 5TMM3VT mice in vivo. Collectively, our data indicate that NAT10 acetylates CEP1 70 mRNA to enhance CEP170 translation efficiency, which suggests that NAT10 may serve as a promising therapeutic target in MM.