ObjectiveTo observe the microbial changes in Wistar rats with liver injury caused by the Dictamni Cortex-Flavescens Sophora by high-throughput sequencing technology and investigate the potential mechanism of liver injury caused by the Dictamni Cortex-Flavescens Sophora. MethodFemale Wistar rats were randomly divided into four groups： normal group， as well as low-dose， medium-dose， and high-dose groups of traditional Chinese medicine （TCM）. The rats were gavaged with the Dictamni Cortex-Flavescens Sophora in different doses （4.125， 8.25， 16.5 g·kg^-1 of raw drug respectively） for 28 days， and the general condition was recorded. The liver-body weight ratio was calculated， and the biochemical indexes of serum were observed. The Hematoxylin-eosin （HE） staining was used to observe pathological changes in the liver， and 16S rDNA high-throughput sequencing was utilized to detect fecal microbial changes in rats. ResultCompared with the normal group， Dictamni Cortex-Flavescens Sophora increased the liver weights and liver-body weight ratios of Wistar rats. The difference in liver weight between the medium-dose and high-dose groups of TCM was statistically significant （P<0.05）， and the liver-body weight ratios of the low-dose， medium-dose， and high-dose groups of TCM were all statistically significant （P<0.05）. Compared with the normal group， serum albumin and cholesterol levels increased in the medium-dose and high-dose groups of TCM （P<0.05）. The histopathology of the liver in the medium-dose and high-dose groups of TCM showed tiny vacuole-like changes. Compared with the normal group， there were obvious intestinal flora disorders after administration of Dictamni Cortex-Flavescens Sophora， and alpha diversity increased in the medium-dose and high-dose groups of TCM. The principal coordinates analysis showed that species increasingly deviated from the normal group as the administered dose increased. Compared with the normal group， the proportion of Firmicutes and Bacteroidota decreased after the drug administration， and the genus level of Parasutterella， Romboutsia， Turicibacter， Allobaculum， and Dubosiella increased. The genus level of Lachnospiraceae_NK4A136_group， Blautia， Erysipelatoclostridium， Muribaculum， and Ruminococcus_gnavus_group decreased. The correlation analysis showed that Parasutterella， Romboutsia， Turicibacter， Allobaculum， and Dubosiella were positively correlated with serum cholesterol and liver-body weight ratio， and lanchnospiraceae_NK4A136_group， Blautia， Muribaculum， Erysipelatoclostridium， and Ruminococcus_gnavus_group were negatively associated with serum cholesterol and liver-body weight ratio. ConclusionThe liver injury caused by Dictamni Cortex-Flavescens Sophora is manifested as a lipid metabolism disorder， and the mechanism is related to the increase in lipid metabolism-related microorganisms.

AIM:To evaluate the therapeutic effect of Shen-Xiankang formula on renal interstitial fibrosis in-duced by unilateral ureteral obstruction(UUO)in mice and to elucidate its underlying mechanisms.METHODS:Thirty-two C57BL/6 mice were randomly divided into sham group,UUO model group,and Shen-Xiankang formula intervention groups receiving either a low dose(150 mg·kg-1·d-1)or a high dose(450 mg·kg-1·d-1),with 8 mice in each group.All mice except those in sham group underwent UUO to establish chronic kidney disease(CKD)model.After modeling,cor-responding doses of Shen-Xiankang or an equivalent volume of saline were administered daily for 7 d.Upon completion of treatment,renal tissues were collected for hematoxylin-eosin(HE)and Masson staining to assess tissue damage and fibro-sis.Immunohistochemistry and Western blot analyses were used to detect the markers of fibrosis,oxidative stress,and fer-roptosis.The effect of Shen-Xiankang formula on the interaction between activating transcription factor 3(ATF3)and Smad3 was assessed using co-immunoprecipitation(Co-IP).RESULTS:The untreated UUO model group exhibited nota-ble pathological changes such as expanded renal tubules and collagen deposition.Shen-Xiankang treatment significantly alleviated these changes(P<0.05).It markedly reduced Smad3 phosphorylation,ATF3,4-hydroxynonenal(4-HNE),and NADPH oxidase 4(NOX4)aberrant expression,while increasing glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)expression.Co-IP results indicated a significant modulation of the ATF3-Smad3 interac-tion by Shen-Xiankang.CONCLUSION:Shen-Xiankang formula effectively mitigates UUO-induced renal interstitial fi-brosis in mice.The mechanism may involve modulating the ATF3/Smad3 interaction,which in turn attenuates oxidative stress and ferroptosis,consequently leading to the amelioration of renal fibrosis.These findings provide important insights for further research and clinical application of Shen-Xiankang formula.

Objective To explore the clinical efficacy of multi-channel functional electrical stimulation cycling ergometer for children with spastic cerebral palsy. Methods A total of 60 children with rehabilitation treatment for spastic cerebral palsy in Outpatient Department were selected and randomly divided into observation group and control group, with 30 cases in each group. The control group received conventional rehabilitation treatments such as exercise therapy, occupational therapy and Chinese medicine massage, while the observation group received multi-channel functional electrical stimulation cycling ergometer training on the basis of the conventional rehabilitation treatments. Before treatment and 12 weeks after treatment, the Gross Motor Function Measure (GMFM-88), Peabody Developmental Measure Scale-Gross Motor (PDMS-GM), Berg Balance Scale (BBS), and Activities of Daily Living (ADL) were used to assess the gross motor function, balance function, and activities of daily living of the children in both groups. Results Before treatment, there were no significant differences in GMFM-88 (D area, E area score, and total score), PDMS-GM (posture score, mobility score, and manipulation score), BBS, and ADL scores between the two groups (P>0.05). After treatment, the GMFM-88 (D area, E area score and total score), PDMS-GM (posture score, mobility score and manipulation score), BBS and ADL scores in both groups improved significantly compared with those before treatment, and all the scores in the observation group were significantly better than those in the control group (P < 0.05). Conclusion Multi-channel functional electrical stimulation cycling ergometer can effectively improve the gross motor function, balance function, and activities of daily living of children with spastic cerebral palsy.

Objective:To investigate the predictors of intracranial hemorrhage in patients with cerebral venous sinus thrombosis (CVST).Methods:Patients with CVST treated in Drum Tower Hospital Affiliated to Medical School of Nanjing University from January 2008 to March 2021 were retrospectively enrolled. The risk factors, clinical manifestations, imaging examination and 90 d follow-up data were collected. The complicated intracranial hemorrhage group and non-intracranial hemorrhage group were compared. Multivariate logistic regression analysis was used to determine the independent predictors of intracranial hemorrhage in patients with CVST. Results:A total of 104 patients with CVST were enrolled, including 42 males and 62 females. Their age was 35.24 ± 10.92 years old (range 22-68 years). Thirty-eight patients (36.84%) were complicated with intracranial hemorrhage, including 34 hemorrhagic cerebral infarction and 4 complicated subarachnoid hemorrhage. Univariate analysis showed that compared with the non-intracerebral hemorrhage group, the intracranial hemorrhage group was more common in puerperal/pregnant patients (60.52% vs. 48.48%; P=0.012), with more acute onset (57.89% vs. 48.48%; P=0.004), focal neurological signs (47.37% vs. 19.70%; P=0.003) and seizure (39.47% vs. 18.18%; P=0.017), and the site of thrombosis was more common in the superior sagittal sinus (57.89% vs. 36.36%; P=0.033). Multivariate logistic regression analysis showed that puerperium/pregnancy (odds ratio 2.857, 95% confidence interval 1.095-7.453; P=0.031) and superior sagittal sinus thrombosis (odds ratio 2.847, 95% confidence interval 1.110-7.302; P=0.027) were the independent predictors of intracranial hemorrhage in patients with CVST. The analysis at 90 d after onset showed that there was no significant difference in the good outcome rate between the intracranial hemorrhage group and the non-intracranial hemorrhage group (86.84% vs. 89.39%; P=0.695). Conclusions:Puerperium/pregnancy and superior sagittalsinus thrombosis are the independent risk factors for intracranial hemorrhage in patients with CVST. However, complicated with intracranial hemorrhage is not associated with 90-day clinical outcomes.

Objective:To study the effect of thioredoxin domain containing protein 5 (TXNDC5)-peroxiredoxin 2 (Prx2) on the drug resistance of prostate cancer cells.Methods:Prostate cancer PC3 cells were cultured in vitro, treated with the chemotherapy drug cyclophosphamide (5, 10, 15 μmol/L) for 24 hours, and PC3 cells without any treatment was served as the control group. The expression levels of TXNDC5 in PC3 cells were detected by real-time fluorescent quantitative PCR (RT-qPCR) and Western blotting. PC3 cells with TXNDC5 knocking down were exposed by cyclophosphamide and CCK-8 was used to detect the cell viability of siTXNDC5 group and siNC group. The content of reactive oxygen free radicals was determined by reactive oxygen detection kit. PC3 cells and its parental cyclophosphamide-resistant ones with TXNDC5 knocking down were treated by 10 μmol/L cyclophosphamide and subjected for CCK8 assay. The expression of Prx2 in PC3 cells was detected by Western blotting after TXNDC5 was silenced. Prx2 expression was silenced in PC3 cells overexpressing TXNDC5, and cell viability and reactive oxygen free radical content were detected in Vec-Ctrl group, pcTXNDC5 group, siNC group, siPrx2 group and pcTXNDC5+ siPrx2 group. Results:Compared with the control group, cyclophosphamide treatment significantly increased the expression of TXNDC5 at mRNA and protein levels in PC3 cells. After PC3 cells were treated with cyclophosphamide (10, 15 μmol/L) for 12 h, compared with the siNC group, the cell viability in the siTXNDC5 group was significantly suppressed (0.44±0.08 vs. 0.74±0.10, t=3.647, P=0.031; 0.30±0.04 vs. 0.53±0.06, t=6.115, P=0.006). When PC3 cells were treated with 10 μmol/L cyclophosphamide for 6 and 12 h, compared with the siNC group, the production of reactive oxygen free radicals in the siTXNDC5 group was significantly increased (2.68±0.19 vs. 1.58±0.26, t=-6.027, P=0.005; 4.56±0.37 vs. 2.73±0.26, t=-6.995, P=0.003). When PC3 cells and its cyclophosphamide-resistant ones were treated with 10 μmol/L cyclophosphamide for 12 h, compared with the siNC group, the cell viability was significantly inhibited in the siTXNDC5 group. Western blotting analysis showed that the expression of Prx2 was significantly reduced when TXNDC5 was silenced. Silencing Prx2 could significantly attenuate the increase of cell viability and the decrease of reactive oxygen content resulting from TXNDC5 overexpression. PC3 cells were treated with 10 μmol/L cyclophosphamide for 12 h, and the cell viabilities of the Vec-Ctrl group, pcTXNDC5 group, siNC group, siPrx2 group and pcTXNDC5+ siPrx2 group were 0.52±0.07, 0.69±0.03, 0.56±0.05, 0.43±0.05, 0.58±0.07, respectively, and there was a statistically significant difference ( F=8.868, P=0.003). Furthermore, the cell viability in the pcTXNDC5+ siPrx2 group decreased significantly when compared to that of the pcTXNDC5 group ( P=0.045). The contents of reactive oxygen free radicals in the above 5 groups were 3.26±0.46, 2.09±0.49, 3.16±0.38, 4.62±0.26, 2.87±0.36, respectively, and there was a statistically significant difference ( F=16.037, P<0.001). The content of reactive oxygen radicals in the pcTXNDC5+ siPrx2 group was higher than that of the pcTXNDC5 group ( P=0.036). Conclusion:TXNDC5 can reduce the level of reactive oxygen free radicals in prostate cancer cells by regulating the expression of Prx2, so as to promote the drug resistance of prostate cancer cells.

Objective:To understand the occupational health status of a lead-acid battery enterprise in Jiangsu Province, to observe the results of blood lead and bone mineral density (BMD) of the workers exposed to occupational lead, and to explore the effect of occupational lead exposure on BMD, so as to provide basis for the prevention and treatment of occupational lead poisoning and osteoporosis.Methods:An occupational health survey was conducted in a lead-acid battery enterprise in Jiangsu Province in January 2019. Basic information and occupational health examination results of 402 persons exposed to occupational lead were collected, and BMD was measured. Spearman rank correlation test was used to analyze the relationship between blood lead and BMD, and logistic regression analysis was used to analyze the influencing factors of BMD.Results:The blood lead level M ( P25, P75) of 402 occupational lead exposure workers was 220.5 (118.0, 307.0) μg/L, 46 workers (11.4%) had blood lead value ≥400 μg/L, and 5 workers (1.2%) ≥600 μg/L. 124 workers (30.8%) had abnormal BMD. The concentrations of lead dust and lead smoke in the workplace were <0.004-0.027 and <0.021-0.045 mg/m 3, respectively. The positions exceeding the standard point were mainly concentrated in the casting and welding group (44.4%, 4/9) of lead smoke positions. There was a statistically significant difference in the overall distribution of blood lead levels among lead exposure workers with different BMD levels, and there was a positive correlation between blood lead and BMD ( P<0.01) . The results of univariate analysis showed that there were statistically significant differences in the distribution of abnormal BMD among workers exposed to different genders, positions and blood lead levels ( P<0.01) . The results of multivariate logistic regression analysis showed that the risk of abnormal BMD in male workers was 5.069 times of that in female worker (95% CI: 2.906-8.840, P<0.01) . Conclusion:Occupational lead exposure personnel have a high blood lead level and a high abnormal BMD rate. Exposure to lead working environment is an influencing factor for the abnormal BMD of workers, so enterprise managers should pay attention to health protection, occupational health monitoring and supervision of working environment of front-line workers.

Objective:To understand the occupational health status of a lead-acid battery enterprise in Jiangsu Province, to observe the results of blood lead and bone mineral density (BMD) of the workers exposed to occupational lead, and to explore the effect of occupational lead exposure on BMD, so as to provide basis for the prevention and treatment of occupational lead poisoning and osteoporosis.Methods:An occupational health survey was conducted in a lead-acid battery enterprise in Jiangsu Province in January 2019. Basic information and occupational health examination results of 402 persons exposed to occupational lead were collected, and BMD was measured. Spearman rank correlation test was used to analyze the relationship between blood lead and BMD, and logistic regression analysis was used to analyze the influencing factors of BMD.Results:The blood lead level M ( P25, P75) of 402 occupational lead exposure workers was 220.5 (118.0, 307.0) μg/L, 46 workers (11.4%) had blood lead value ≥400 μg/L, and 5 workers (1.2%) ≥600 μg/L. 124 workers (30.8%) had abnormal BMD. The concentrations of lead dust and lead smoke in the workplace were <0.004-0.027 and <0.021-0.045 mg/m 3, respectively. The positions exceeding the standard point were mainly concentrated in the casting and welding group (44.4%, 4/9) of lead smoke positions. There was a statistically significant difference in the overall distribution of blood lead levels among lead exposure workers with different BMD levels, and there was a positive correlation between blood lead and BMD ( P<0.01) . The results of univariate analysis showed that there were statistically significant differences in the distribution of abnormal BMD among workers exposed to different genders, positions and blood lead levels ( P<0.01) . The results of multivariate logistic regression analysis showed that the risk of abnormal BMD in male workers was 5.069 times of that in female worker (95% CI: 2.906-8.840, P<0.01) . Conclusion:Occupational lead exposure personnel have a high blood lead level and a high abnormal BMD rate. Exposure to lead working environment is an influencing factor for the abnormal BMD of workers, so enterprise managers should pay attention to health protection, occupational health monitoring and supervision of working environment of front-line workers.

Objective:To evaluate the safety and effectiveness of tranexamic acid in the treatment of spontaneous intracerebral hemorrhage.Methods:Patients with spontaneous intracerebral hemorrhage admitted to the Departments of Emergency and Neurology, Nanjing Drum Tower Hospital from December 2015 to December 2018 were enrolled prospectively. The patients were randomly divided into two groups according to a random number table: tranexamic acid group and control group. All patients received conventional treatment. On this basis, 1 g of tranexamic acid injection was given to the tranexamic acid group, dissolved in 100 ml of normal saline, intravenous injection for 10 min; then 1 g of tranexamic acid was given, dissolved in 250 ml of normal saline, intravenous drip for 8 h. The control group was given an equal volume of normal saline. The main outcome measures were good outcome (defined as modified Rankin Scale score0-2) and mortality at 90 d after treatment. The secondary outcome was hematoma enlargement at 24 h after treatment and the National Institutes of Health Stroke Scale (NIHSS) score at 7 and 30 days after treatment. Platelet count and fibrinogen level were measured before treatment and 4 h after the infusion of tranexamic acid. Various adverse events were monitored.Results:A total of 150 patients were included, including 83 males (55.3%). There were 73 patients in the tranexamic acid group and 77 in the control group. There was no statistically significant difference in baseline data between the two groups. The rate of good outcome in the tranexamic acid group at 90 d was significantly higher than that in the control group (57.5% vs. 40.3%; χ2=4.476, P=0.034), while there were no significant differences in mortality rate (0% vs. 1.3%; Fisher's exact test P=1.000) and the proportion of patients with hematoma enlargement at 24 h (6.8% vs. 15.6%; χ2=2.845, P=0.092). The NIHSS score at 7 d (9.26±3.35 vs. 11.68±4.25; t=3.859, P<0.001) and at 30 d (5.45±2.52 vs. 7.38±3.28; t=4.030, P<0.001) in the tranexamic acid group were significantly lower than those of the control group. Fibrinogen in the tranexamic acid group increased significantly after treatment compared with baseline (4.20±0.56 g/L vs. 3.33±0.60 g/L; t=8.997, P<0.001), and was significantly higher than that in the control group after treatment (4.20±0.56 g/L vs. 3.30±0.55 g/L; t=9.906, P<0.001). No adverse events such as venous thromboembolism, ischemic events, and seizures were observed. Conclusion:Tranexamic acid can promote the recovery of neurological function, and improve the outcome of patients with acute spontaneous intracerebral hemorrhage, and the safety is good.

Objective:To investigate the effect of cocaine- and amphetamine-regulated transcript peptide (CART) on the synapse structure of mice cortical neuron subjected to oxygen-glucose deprivation (OGD).Methods:Primary neurons of the embryonic cerebral cortex obtained from healthy and clean Kunming mice at gestational age of 16-17 d were cultured. They were divided into control group, CART group, OGD group, and OGD+ CART group. 0.4 nmol/L CART 55-102 was added and cultured for 12 h after OGD treatment in the OGD+ CART group; the CART group was given the same dose of CART 55-102. The neuronal mortality was measured by the flow cytometry. The changes of synaptic structure were observed by immunofluorescence analysis, and the axon length and synapsin Ⅰ positive area were quantitatively analyzed. Real-time fluorescent quantitative polymerase chain reaction and Western blot analysis were used to identify the brain-derived neurotrophic factor (BDNF) mRNA and protein expression. Results:Compared with the control group, the mortality of neurons in the OGD group was significantly increased, the neuronal synapse growth was significantly inhibited, the positive area of synapsin Ⅰ was significantly reduced, and the expression levels of BDNF mRNA and protein were significantly down-regulated (all P<0.05). Compared with the OGD group, adding CART 55-102 significantly reduced the mortality of OGD neurons ( P<0.05), reversed the inhibitory effect of OGD on neuronal synapse growth, significantly increased the length of neuron axons and the positive area of synapsin Ⅰ (all P<0.05), and significantly up-regulated BDNF mRNA and protein expression levels (all P<0.05). Conclusion:CART can protect the synaptic structure of mice cortical neuron subjected to OGD, and its mechanism may be related to the up-regulation of BDNF expression.

OBJECTIVE: To investigate the efficacy of brain-targeted rapamycin (T-Rap) in treatment of epilepsy in rats. METHODS: Rapamycin nanoparticles targeting brain were prepared. The epilepsy model was induced by injection of pilocarpine in rats. The rats with pilocarpine-induced epilepsy were treated with rapamycin (Rap group) or brain-targeted rapamycin (T-Rap group). Seizure activity was observed by electroencephalography; the effect on mTOR signaling pathway was detected by Western blot; neuronal death and moss fiber sprouting were analyzed by Fluoro-Jade B (FJB) and Timm's staining, respectively. RESULTS: Electroencephalography showed that both preparation of rapamycin significantly reduced the frequency of spontaneous seizures in rats, and the effect of T-Rap was stronger than that of conventional rapamycin (<0.05). Western blot showed that the phosphorylation levels of S6K and S6 in T-Rap group were lower than those in Rap group (all <0.05), indicating that T-Rap had a stronger inhibitory effect on mTOR signaling pathway. FJB staining showed that T-Rap significantly decreased neuronal death, but there was no significant difference as compared with Rap group. Timm's staining showed that both preparations of rapamycin significantly reduced the germination of mossy fibers, while the effect of T-Rap was more pronounced than Rap group (<0.05). The inhibition of body weight gain of T-Rap group was less than that of Rap group (<0.05). CONCLUSIONS T-Rap has a better therapeutic effect on epilepsy than conventional rapamycin with a less adverse effects in rats.
Animals ; Brain ; drug effects ; Disease Models, Animal ; Epilepsy ; chemically induced ; drug therapy ; Neurons ; drug effects ; Pilocarpine ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Sirolimus ; pharmacology ; therapeutic use ; Treatment Outcome