Objective To investigate the reproductive and developmental effects of Clothianidin in rats. Methods Clothianidin was administrated by diet to both parental and first filial (F 1) generations of rats at the dosages of 0, 30.51, 110.84 and 304.26 mg/(kg·d) in females, and 0, 26.45, 92.69 and 279.42 mg/(kg·d) in males. Clothianidin was administered through diet to male and female rats for 8 weeks before mating. Clothianidin was administered to female rats in the parental and F1 generations during mating, gestation and lactation periods. During the test, toxicity performance was observed, reproduction index was calculated, and pathological examination was carried out. Results The body weights of rats in the parent and F1 generations in the high-dose group were lower than those in the control group during pre-mating exposure and at various time points during pregnancy and lactation (P<0.05). The pregnancy rates of parental and F1 generations in the high-dose group were lower than those of the control group (48.57% vs 71.43%, 45.71% vs 80.00%, P＜0. 05). Sperm concentration and sperm motility of the parental generation were lower than those of the control group [(42.55±12.87) vs (53.84±7.65) ×106/ml, (58.94±10.59) vs (65.59±6.03), （P＜0.05）]. Sperm concentration and sperm motility of the F1 generation were lower than those of the control group [(41.64±12.42) vs (53.09±9.48), (55.13±9.19) vs (64.53±6.31), (P＜0.05). Conclusion Exposure to clothianidin has reproductive toxicity to Wistar rats, and the no-observed adverse effect level (NOAEL) in the two-generation reproductive toxicity test is 92.69 mg/kg·BW for males and 110.84 mg/kg·BW for females in Wistar rats.

A retrospective investigation was conducted to analyze the occupational exposure history, clinical manifestations, laboratory tests, imaging findings, and diagnosis and treatment of two cases of sequential latent occupational acute organotin poisoning. Both patients were successively employed in the same enterprise, engaged in crushing of waste polyvinyl chloride plastics, and thus potentially exposed to organotin hazards. Within several days of employment, both patients developed discomfort symptoms, and central nervous system impairment was observed, including short-term memory loss, slow response, and cognitive dysfunction. Hypokalemia was detected in both cases. Cranial magnetic resonance imaging showed abnormalities (multiple ischemic lesions in the bilateral frontal and parietal lobes), and urinary tin was positive. Symptoms relieved in both patients after treatments with tin-exclusion, potassium supplementation, and neurotrophic treatment. Based on the GBZ 26-2007 Diagnostic Criteria of Occupational Acute Trialkyltin Poisoning, and combined with worksite survey of occupational health and exclusion of cerebrovascular disease, viral encephalitis, and autoimmune encephalitis and other neurological disorders, both patients were diagnosed with mild occupational acute trialkyltin poisoning. Sequential latent occupational acute organotin poisoning is prone to misdiagnosis, with great difficulty in etiological identification. Comprehensive assessment of occupational exposure history and biomarker testing are essential for differential diagnosis. Early recognition and intervention improve prognosis, highlighting the need for strengthened occupational health supervision and protection in high-risk work posts.

Objective:To analyse the effect of ultrasound-guided percutaneous liver biopsy and the coaxial biopsy needle tract radiofrequency ablation on patients diagnosed with hepatocellular carcinoma who are considered to be at risk of bleeding.Methods:The data of 117 patients with hepatocellular carcinoma who underwent coaxial biopsy needle tract radiofrequency ablation after ultrasound-guided percutaneous liver biopsy in Peking University First Hospital from March 2019 to April 2023 were retrospectively analysed. There were 95 males and 22 females, with the age of (62.0±11.8) years. A comprehensive analysis was conducted on the following variables: the pre-puncture platelet count, the international standardised ratio, anticoagulation therapy, the haemoglobin (Hb) level, the success rate of the liver puncture, the qualified rate of liver puncture specimens, the number of puncture samples, the length of hospital stay, the Hb level after puncture, bleeding within 10 days post-operation, and complications after ablation, including biliary fistula, hemothorax and organ perforation.Results:Among the 117 patients, 60 cases (51.3%) had an international normalized ratio >1.1, 40 cases (34.2%) had thrombocytopenia, that is, <150×10 9/L, and 17 cases (14.5%) received continuous anticoagulation therapy before the operation. It is evident that all 117 patients successfully completed the ultrasound-guided percutaneous liver biopsy, and that all liver biopsy specimens were qualified. The absence of biliary fistula, hemothorax, organ perforation or death in the patients post-ablation was noted. According to the adverse event evaluation criteria, version 5.0, 113 cases (96.6%) were classified as grade 1 and 4 cases (3.4%) were classified as grade 3. The Hb concentration of patients with minor bleeding (grade 1) prior to puncture was (119.7±22.2) g/L, which was significantly higher than the Hb concentration of patients with severe bleeding (grade 3), (76.0±10.4) g/L ( t=3.92, P=0.010). A meticulous examination of the data revealed that there were no statistically significant differences between the two groups with regard to pre-puncture platelet count, pre-puncture international standardised ratio, pre-puncture proportion of receiving anticoagulant drugs, length of hospital stay and number of puncture samples (all P>0.05). Conclusion:For patients with hepatocellular carcinoma who are at risk of bleeding, ultrasound-guided percutaneous liver biopsy followed by coaxial biopsy needle tract radiofrequency ablation can obtain satisfactory liver tissue samples and is relatively safe. There were differences in hemoglobin levels before puncture among patients with different bleeding after puncture.

Objective:To investigate the relationship between lumbar disc herniation and vertebral bone mineral density(BMD)of quantitative analysis of computed tomography(CT).Methods:Eighty patients with lumbar disc herniation who admitted to Beijing Tongzhou District Hospital of Integrated Traditional Chinese and Western Medicine from May 2022 to June 2024 were included in the case group,and 30 healthy volunteers who underwent physical examination in hospital were included in the healthy control group during the same period.The vertebral BMD of all subjects was quantitatively analyzed by CT.The data,lumbar BMD value,lumbar bone mass loss and osteoporosis distribution of the two groups were compared at baseline.Results:There were no significant differences in gender,age,body mass index(BMI)and abdominal circumference of baseline data between the case group and the healthy control group(P>0.05).The BMD value of the fourth lumbar vertebra(L4)in the case group was lower than that in the healthy control group,and the difference was statistically significant(t=1.991,P<0.05).There were no significant differences in BMD value and mean BMD(Lmean BMD)of the fifth lumbar vertebra(L5)between the case group and the healthy control group(P>0.05).There was no statistically significant difference in the lumbar BMD value of healthy control group between different genders(P>0.05),and there was significant difference in Lmean BMD between different genders in the case group(t=2.063,P<0.05),while there were no statistically significant difference in the L4 BMD and L5 BMD of the case group between different genders(P>0.05).The difference of Lmean BMD values of the persons with same gender(male,female)between the case group and the healthy control group were statistically significant(t=2.570,3.300,P<0.05).The ratio of normal lumbar bone mass in the case group was 48.75%,which was lower than that in the healthy control group(70.00%),and the difference was statistically significant(x2=3.974,P<0.05).The ratio of osteoporosis in the case group was 18.75%,which was higher than that in the healthy control group(3.33%),and the difference of that between two groups was significant(x2=4.172,P<0.05).There was no significant difference in the ratio of bone mass loss between the two groups(P>0.05).Conclusion:CT quantitative analysis shows that the vertebral BMD value of the patients with lumbar disc herniation is significantly lower than that of persons of the healthy control group,which indicates that the decrease of BMD value might be related to the occurrence of lumbar disc herniation.

Objective To explore the mechanism of Tongluo Baoshen Decoction in improving podocyte injury in rats with IgA nephropathy based on Gprc5b/NF-κB/NLRP3 pathway.Methods Totally 130 SPF-grade male SD rats were randomly divided into a normal group(n=20)and a modeling group(n=110).The IgA nephropathy model was established using a compound modeling method,and 100 modeling rats were randomly divided into model group,losartan potassium group(5 mg/kg),and Tongluo Baoshen Decoction low-,medium-,and high-dosage groups(5.3,10.6,21.2 g/kg),with 20 rats in each group.The administration group was given the corresponding dosage of medication by gavage,while the normal group and model group were given an equal amount of distilled water by gavage once a day.After 4 and 8 weeks of administration,urine samples were collected for 24 hours,and blood and kidney tissue specimens were collected.24-hour urinary protein quantification(24 h-UTP),urinary Nephrin,serum creatinine(SCr),blood urea nitrogen(BUN)and blood uric acid(BUA)contents were detected;RT-qPCR and Western blot were used to detect the expressions of G protein coupled receptor C-family 5b(Gprc5b),nuclear factor(NF)-κB p50,NOD like receptor protein 3(NLRP3),Caspase-1,interleukin(IL)-1β,Nephrin mRNA and protein in renal tissue,respectively;HE,PAS,PASM,Masson staining were used to observe the morphology of renal tissue,immunofluorescence was used to observe IgA deposition in the mesangial area of renal tissue,and transmission electron microscopy was used to observe the ultrastructure of podocytes.Results Compared with the normal group,the model group rats showed significantly increased contents of 24 h-UTP,urinary Nephrin and BUA(P<0.01),the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue were significantly increased(P<0.01),while the mRNA and protein expressions of Nephrin were significantly decreased(P<0.01),with mild to moderate proliferation of mesangial cells in the glomerulus,increased mesangial matrix,and immunofluorescence showed clustered and linear deposition of IgA in the mesangial area,electron microscopy showed partial fusion of the foot processes.Compared with the model group,the 24 h-UTP and urinary Nephrin contents in different dosage groups of Tongluo Baoshen Decoction and the losartan potassium group after 4 and 8 weeks administration significantly decreased(P<0.01),with a decrease in BUA content in Tongluo Baoshen Decoction high-dosage group(P<0.05),the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue of Tongluo Baoshen Decoction groups and losartan potassium group decreased(P<0.05,P<0.01),while the mRNA and protein expressions of Nephrin increased(P<0.05,P<0.01),with the proliferation of mesangial cells,the increase of mesangial matrix,the deposition of IgA in the mesangial area,and the fusion of foot processes in renal tissue were alleviated to varying degrees in different dosage groups of Tongluo Baoshen Decoction,with the most significant improvement observed in the high-dosage group.Compared with the 4-week administration,Tongluo Baoshen Decoction high-dose group showed further reductions in 24 h-UTP and urinary Nephrin contents after 8 weeks of administration(P<0.01),further decreases in the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue(P<0.05,P<0.01),and further increases in the mRNA and protein expressions of Nephrin(P<0.01).Conclusion Tongluo Baoshen Decoction can reduce proteinuria,alleviate renal tissue lesions and improve podocyte injury in IgA nephropathy rats,and its mechanism may be related to the inhibition of Gprc5b/NF-κB/NLRP3 pathway in renal tissue.

Objective To observe the therapeutic effects of Tongluo Baoshen Prescription on IgA nephropathy rats;To explore its mechanism.Methods Totally 130 SD rats were randomly divided into a normal group(20 rats)and a modeling group(110 rats).After establishing the IgA nephropathy model,the modeling group was further randomly divided into the model group,losartan potassium group and Tongluo Baoshen Prescription low-,medium-and high-dosage groups,with 20 rats in each group.Tongluo Baoshen Prescription low-,medium-and high-dosage groups were administered at dosages of 5.3,10.6 and 21.2 g/kg respectively,the losartan potassium group was given with the dosage of 5 mg/kg,the normal group and model group were given an equivalent amount of distilled water by gavage once daily.Blood,urine and kidney tissue samples were collected after 4 and 8 weeks of administration.The hemoglobin content was detected,urinary IL-1β,integrin α3β1 and serum albumin contents were detected by ELISA,and the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue were detected by RT-qPCR and Western blot,the apoptosis of renal tissue at 8 weeks of administration was detected by TUNEL staining,the expression of C3c in renal tissue was detected by immunofluorescence,the co-expression of Gprc5b,Caspase-1,NLRP3 and Nephrin were detected by immunofluorescence double labeling,the expression of Gprc5b and Nephrin in renal tissue were detected by immunohistochemistry.Results Compared with the normal group,the model group rats showed significantly increased contents of urinary IL-1β and integrin α3β1(P<0.01),with further increases in urinary integrin α3β1 over time(P<0.05);the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue significantly increased(P<0.01),and the proportion of apoptosis-positive cells in renal tissue significantly increased(P<0.01),immunofluorescence results revealed that C3c exhibited granular and clumpy high-intensity deposition in the mesangial area and capillary loops of the glomeruli(P<0.01),immunofluorescence double labeling showed that the expression of Gprc5b,Caspase-1 and NLRP3 in renal tissue increased(P<0.01),while Nephrin expression significantly decreased(P<0.01),immunohistochemistry analysis showed that the positive expression of Gprc5b in renal tissue significantly increased(P<0.01),while Nephrin significantly decreased(P<0.01).Compared with the model group,the urinary IL-1β and integrin α3β1 contents in the losartan potassium group and Tongluo Baoshen Prescription groups reduced after 4 and 8 weeks of treatment(P<0.05,P<0.01);the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue decreased(P<0.05,P<0.01),and the proportion of apoptosis-positive cells in renal tissue decreased(P<0.05),the C3c deposition in renal tissue was diminished(P<0.05,P<0.01),immunofluorescence double labeling showed that the expression of Gprc5b,Caspase-1 and NLRP3 in renal tissue were decreased(P<0.05,P<0.01),while Nephrin expression increased(P<0.05,P<0.01),immunohistochemistry analysis showed that the positive expression of Gprc5b in renal tissue decreased(P<0.05,P<0.01),while Nephrin expression increased(P<0.05,P<0.01).Conclusion Tongluo Baoshen Prescription has a protective effect on the kidney of IgA nephropathy rats,and it can improve podocyte injury.The mechanism may be related to the inhibition of the Gprc5b/NF-κB/NLRP3 pathway.

Cancer cachexia is a complex syndrome caused by multiple factors,which seriously affects the quality of life and prognosis of patients.Its overall pathogenesis is related to the deficiency of spleen qi,insufficiency of kidney essence,internal generation of turbid toxins,and the obstruction of the production of qi,blood and essential qi,which cannot nourish the muscles and bones.Under the guidance of the dynamic diagnosis and treatment system of"spleen and kidney exhaustion as the root cause and internal accumulation of turbid toxins as the manifestation",the overall regulation is carried out from four dimensions:opening and closing the spleen and stomach,nourishing the kidney and promoting transportation,transforming turbid toxins and detoxification,and tonifying qi and nourishing yin.It has shown unique value in the intervention of cancer cachexia and can provide ideas and references for the clinical practice of TCM in treating cancer cachexia.

Objective:To study the subacute oral toxic effect of p-chloro-m-xylphenol on rats and provide a basis for its safety evaluation.Methods:SPF-grade Wistar rats were randomly divided into 4 groups according to body weight stratification randomization, with 20 rats in each group, half male and half female. The set concentrations of the p-chloro-m-xylphenol dose groups were 11.25, 22.50, and 45.00 mg/kg·BW respectively, with an intragastric volume of 10 ml/kg·BW. The blank control group was given the same amount of distilled water. The rats were treated with intragastric administration for 30 days. After intraperitoneal injection of 50 mg/kg·BW pentobarbital sodium for anesthesia, bloodletting and death, the organs were separated and weighed. Blood was collected from the abdominal aorta to determine the hematological and serum biochemical indicators of the whole blood of rats. Multiple groups comparison was performed by one-way analysis of variance, and pairwise comparison between groups was performed by the least significant difference test or Dunnett-t3 test.Results:The kidney weight in the 45.00 mg/kg·BW dose group of female rats [ (1.59±0.11) g] was lower than that in the blank control group [ (1.71±0.12) g], and the difference was statistically significant ( P<0.05) . The percentage of monocytes in the 11.25 mg/kg·BW dose group of male rats [ (4.81±0.74) %] was lower than that in the blank control group [ (5.86±0.58) %], the red blood cell count [ (6.93±0.26) ×10 12/L] and hemoglobin [ (134.30±4.95) g/L] in the 22.50 mg/kg·BW dose group of female rats were both lower than those in the blank control group[ (7.48±0.26) ×10 12/L, (146.20±4.42) g/L], the percentage of eosinophils in the 11.25 mg/kg·BW dose group of female rats [ (2.46±0.86) %] was higher than that in the blank control group [ (1.66±0.41) %], and the differences were statistically significant ( P<0.05) . Conclusion:P-chloro-m-xylphenol may have toxic effects on the blood system of rats, and the kidneys may be the potential target organs for its toxicity.

Objective:To analyze the epidemiological characteristics and influencing factors of single-cigarette use and dual cigarette-cigar use in China.Methods:This study was a cross-sectional study that selected 85 638 urban and rural residents who met the inclusion criteria from the 2018 China Health Literacy Survey as research subjects. An analysis was conducted on 21 849 users of cigarettes and cigars among them. Due to the small number of individuals who exclusively used cigars (247 cases), the research subjects were divided into two categories: exclusive cigarette users and dual users of cigarettes and cigars. The groups were categorized by age (18-34 years, 35-54 years, ≥55 years), gender (male, female), education level (primary school and below, junior high school and high school, university and above) and annual household income (<20 000 yuan, 20 000-<80 000 yuan, ≥80 000 yuan) to compare the tobacco usage rate and conduct subgroup analyses for each subgroup. Multivariate logistic regression analysis was employed, incorporating general demographic characteristic information to explore the influencing factors of exclusive cigarette use and dual use of cigarettes and cigars, respectively.Results:The rate of exclusive cigarette use in our country was 24.3%, while the dual use rate of cigarettes and cigars was 0.9%. The exclusive cigarette use rate and the dual use rate of cigarettes and cigars among males were significantly higher than those among females (48.25% vs 2.48%, and 1.84% vs 0.06%) (both P<0.001). For males, the high-risk factors for exclusive cigarette use included living in urban areas ( OR: 1.37, 95% CI: 1.23-1.54), being Han ethnicity ( OR: 1.73, 95% CI: 1.51-1.98), and having an annual household income ≥20 000 yuan ( OR: 1.54, 95% CI: 1.38-1.82) while having a junior high school education or higher was a protective factor ( OR: 0.68, 95% CI: 0.52-0.90). Age≥35 years ( OR: 3.36, 95% CI: 2.62-4.32) and having a junior high school education or higher ( OR: 1.30, 95% CI: 1.02-1.67) were risk factors for dual use of cigarettes and cigars in males. Among females, living in urban areas ( OR: 1.53, 95% CI: 1.19-1.97) and being Han ethnicity ( OR: 5.96, 95% CI: 4.47-7.96) were risk factors for exclusive cigarette use, while having a university education or higher was a protective factor ( OR: 0.28, 95% CI: 0.18-0.42). However, for female dual use of cigarettes and cigars, no significant effects were observed for any demographic characteristics. Conclusions:The use rate of cigarettes alone in China is significantly higher than that of cigarette-cigar dual use, and the rates of cigarette use alone and cigarette-cigar dual use in men are significantly higher than those in women. Tobacco use is being affected by sociodemographic factors, among which place of residence, ethnicity and education level are the main influencing factors of cigarette use alone, and gender, age and education level are the main influencing factors of cigarette-cigar dual use.

Objective:To investigate the efficacy and potential mechanism of sulfasalazine (SASP) therapy for intrahepatic cholestasis.Methods:Forty SD rats were randomly divided into a normal group (carboxymethylcellulose sodium 0.5%), a model group (carboxymethylcellulose sodium 0.5%), a SASP group (sulfasalazine 150 mg/kg), and an ursodeoxycholic acid (UDCA 100 mg/kg) group, with ten rats in each group. The cholestatic liver injury model was induced using α-naphthylisothiocyanate. Blood samples were collected to detect liver biochemistry and cholestasis indexes. Rat liver tissue was collected for hematoxylin-eosin staining and Mason staining. Liver tissue was analyzed using transcriptome sequencing, real-time reverse transcription quantitative polymerase chain reaction, Western blotting and flow cytometry. Simultaneously, the level of inflammatory factors, total cholesterol, and total bile acids were measured in liver tissue. A t-test or a nonparametric test was selected based on the distribution and variance characteristics of the data. Results:The serum levels of alanine aminotransferase [(386.88±155.77) U/L], aspartate aminotransferase [(593.13±251.44) U/L], alkaline phosphatase [(561.25±167.54) U/L], total bilirubin [(38.00±29.75) mol/L] and total bile acids [(191.31±91.48) mol/L] were significantly lower in the SASP than the model groups [(778.75±313.59) U/L, (1 159.38±274.62) U/L, (801.25±161.28) U/L, (86.63±27.83) mol/L, (432.63±151.54) mol/L, P<0.05]. Liver histopathology showed that the inflammatory cells in the manifold area, the bile duct proliferation and dilation, and the collagen deposition in the manifold area were significantly improved under the pathological state of cholestasis in the SASP group. The results of transcriptome sequencing demonstrated that SASP activated the peroxisome proliferator actived receptor α (PPAR α) and inhibited Th17 cell differentiation. The PPARα mRNA level in the liver tissue of rats was significantly increased in the SASP group compared with that in the model group [(0.41±0.28) vs. (0.16±0.04), P<0.05], and the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase was decreased compared with that in the model group [(3.09±1.16) vs. (8.19±2.19), P<0.05], which was also verified at the protein level. The concentrations of total cholesterol [(0.31±0.34) mmol/g] and total bile acids [(2.58±0.99) μmol/g] were lower than the model group [(0.83±0.62) mmol/g and (4.07±0.91) μmol/g] ( P<0.05), and at the same time it was accompanied by lower levels of inflammatory factors ( P<0.05). SASP treatment decreased the expression of retinoic acid receptor-related orphan receptor γt gene ( P<0.05) and the proportion of Th17 ( P<0.05). Conclusion:SASP can improve cholestatic liver injury, and its mechanism is related to the activation of peroxisome proliferator-activated receptor α and the inhibition of Th17 cell differentiation.