Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective To investigate the role of long non-coding RNA-small nucleolar RNA host gene 3(lncRNA-Snhg3)and its regulatory mechanism in the hepatic glucose metabolism of mice.Methods Adenovirus Snhg3 was over-expressed by the tail vein injection in db/db mice,and then glucose tolerance and pyruvate tolerance were meas-ured.The mRNA expression of mouse liver gluconeogenesis-related genes phosphoenolpyruvate carboxylase(Pepck)and glucose-6-phosphatase(G6pc)and stress-inducing protein 2(Sestrin2,Sesn2,a gene adjacent to Snhg3)were de-tected by RT-qPCR.The dual luciferase reporter assay was used to detect the effect of Snhg3 on the Sesn2 promoter activity in 293T cells.Results Snhg3 over-expression improved glucose tolerance and pyruvate tolerance in db/db mice.Snhg3 over-expression inhibited the mRNA of gluconeogenesis genes of Pepck(P＜0.05)and G6pc(P＜0.05),while promoted the mRNA of Sesn2(P＜0.01).Meanwhile,Snhg3 over-expression promoted Sesn2 promoter activity in 293T cells(P＜0.05).Conclusions Snhg3 improves glucose metabolism in mice by promoting Sestrin2 expression.

Objective To investigate the regulation of synaptic plasticity by cannabinoid receptor 1(CB1R)and its effects on autism spectrum disorder(ASD)-like behavior.Methods CB1R-knockout(KO)mice and valproic acid(VPA)-induced ASD model mice(VPA mice)were used as study subjects.Behavioral experiments were used to assess the effects of CB1R on ASD-like behavior in mice,neuronal structural integrity and dendritic density were detected by microtubule-associated protein 2(MAP2)staining experiments,and the expression of synapse-associated proteins was detected by Western blot,to assess the effects of CB1R on synaptic plasticity.Results Behavioral result showed that VPA mice demonstrated significant ASD-like behavior,while CB1R-/-mice spent a significantly smaller proportion of residence time in the central region of the open field(P＜0.0001),showed significant increases in the number of marbles buried and self-grooming time(P＜0.01),significantly less time spent socializing with unfamiliar mice 2 and exploring unfamiliar objects(P＜0.001),and significantly more time exploring old objects(P＜0.05).The relative dwelling time was significantly reduced in CB1R+/-mice(P＜0.001),and the number of marbles buried and self-grooming time were significantly increased(P＜0.05).Synaptic plasticity assays revealed significant synaptic plasticity impairment in VPA mice.Hippocampal MAP2-positive neuron densities were significantly reduced in CB1R-/-and CB1R+/-mice,and expression levels of synapsin-1 were significantly increased(P＜0.05).Conclusions CB1R KO leads to ASD-like behavior such as anxiety and repetitive stereotyped behavior,social and cognitive impairments,as well as neuronal damage,dendritic dysplasia and disrupted synaptic protein expression in mice,suggesting that CB1R is involved in regulating synaptic plasticity as a pathological mechanism for the development of ASD-like behavior.

Objective:To study the characteristics of soil microbial composition in sheep sheds in agricultural and pastoral areas, and explore potential zoonotic pathogen species.Methods:Using cross-sectional survey method, soil samples from sheep sheds in the agricultural and pastoral areas of Darhan-Muminggan Joint County, Baotou City, Inner Mongolia Autonomous Region were collected from August to October 2023. Genomic DNA was extracted, and metagenomic second-generation sequencing was conducted. Microbial species annotation was carried out by Kaiju method, and the soil microbial composition and zoonotic pathogen species of sheep sheds in agricultural and pastoral areas were analyzed.Results:A total of 10 and 5 soil samples were collected from sheep sheds in agricultural and pastoral areas, respectively. The results of β diversity analysis showed that there was a significant separation trend in soil samples from sheep sheds in agricultural and pastoral areas, and the interpretation of principal co-ordinates analysis (PCoA) 1 and PCoA2 were 27.8% and 17.4%, respectively. There was no significant difference in the microbial composition of soil samples from sheep sheds in agricultural and pastoral areas ( R = 0.09, P = 0.242). At the phylum level, the dominant bacterial phyla were Actinobacteria, Proteobacteria, Firmicutes, and Bacteroidetes. At the genus level, the dominant bacterial genera were Corynebacterium, Luteimonas, Atopostipes, and Salinicoccus. A variety of zoonotic pathogens were detected, including Brucella melitensis, Mycobacterium tuberculosis, and Clostridium tetani in 15 soil samples. Conclusion:The soil microorganisms in sheep sheds in agricultural and pastoral areas are diverse, and zoonotic pathogens such as Brucella melitensis, Mycobacterium tuberculosis, and Clostridium tetani are detected.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective:To study the characteristics of soil microbial composition in sheep sheds in agricultural and pastoral areas, and explore potential zoonotic pathogen species.Methods:Using cross-sectional survey method, soil samples from sheep sheds in the agricultural and pastoral areas of Darhan-Muminggan Joint County, Baotou City, Inner Mongolia Autonomous Region were collected from August to October 2023. Genomic DNA was extracted, and metagenomic second-generation sequencing was conducted. Microbial species annotation was carried out by Kaiju method, and the soil microbial composition and zoonotic pathogen species of sheep sheds in agricultural and pastoral areas were analyzed.Results:A total of 10 and 5 soil samples were collected from sheep sheds in agricultural and pastoral areas, respectively. The results of β diversity analysis showed that there was a significant separation trend in soil samples from sheep sheds in agricultural and pastoral areas, and the interpretation of principal co-ordinates analysis (PCoA) 1 and PCoA2 were 27.8% and 17.4%, respectively. There was no significant difference in the microbial composition of soil samples from sheep sheds in agricultural and pastoral areas ( R = 0.09, P = 0.242). At the phylum level, the dominant bacterial phyla were Actinobacteria, Proteobacteria, Firmicutes, and Bacteroidetes. At the genus level, the dominant bacterial genera were Corynebacterium, Luteimonas, Atopostipes, and Salinicoccus. A variety of zoonotic pathogens were detected, including Brucella melitensis, Mycobacterium tuberculosis, and Clostridium tetani in 15 soil samples. Conclusion:The soil microorganisms in sheep sheds in agricultural and pastoral areas are diverse, and zoonotic pathogens such as Brucella melitensis, Mycobacterium tuberculosis, and Clostridium tetani are detected.

Objective To investigate the regulation of synaptic plasticity by cannabinoid receptor 1(CB1R)and its effects on autism spectrum disorder(ASD)-like behavior.Methods CB1R-knockout(KO)mice and valproic acid(VPA)-induced ASD model mice(VPA mice)were used as study subjects.Behavioral experiments were used to assess the effects of CB1R on ASD-like behavior in mice,neuronal structural integrity and dendritic density were detected by microtubule-associated protein 2(MAP2)staining experiments,and the expression of synapse-associated proteins was detected by Western blot,to assess the effects of CB1R on synaptic plasticity.Results Behavioral result showed that VPA mice demonstrated significant ASD-like behavior,while CB1R-/-mice spent a significantly smaller proportion of residence time in the central region of the open field(P＜0.0001),showed significant increases in the number of marbles buried and self-grooming time(P＜0.01),significantly less time spent socializing with unfamiliar mice 2 and exploring unfamiliar objects(P＜0.001),and significantly more time exploring old objects(P＜0.05).The relative dwelling time was significantly reduced in CB1R+/-mice(P＜0.001),and the number of marbles buried and self-grooming time were significantly increased(P＜0.05).Synaptic plasticity assays revealed significant synaptic plasticity impairment in VPA mice.Hippocampal MAP2-positive neuron densities were significantly reduced in CB1R-/-and CB1R+/-mice,and expression levels of synapsin-1 were significantly increased(P＜0.05).Conclusions CB1R KO leads to ASD-like behavior such as anxiety and repetitive stereotyped behavior,social and cognitive impairments,as well as neuronal damage,dendritic dysplasia and disrupted synaptic protein expression in mice,suggesting that CB1R is involved in regulating synaptic plasticity as a pathological mechanism for the development of ASD-like behavior.

Objective To analyze the trends,cooperation,topics and hotspots of researches about multi-level rehabilitation service system in China. Methods The literature on multi-level rehabilitation service system in China was searched and screened in databases of CNKI from 1983 to 2023.The number of the articles was described,and the cooperation,research hotspots and changing trend were analyzed using VOSviewer. Results A total of 4 643 articles were included.The number of the articles tended to increase and developed in stages.Nine groups with five or more researchers were found,and seven of them cooperated with each other.The most frequent keywords were community-based rehabilitation(occurrence 1 251 with connection strength 1 780),stroke(occurrence 674 with connection strength 1 126),family rehabilitation(occurrence 412 with connection strength 514),rehabilitation nursing(occurrence 178 with connection strength 240)and quality of life(occur-rence 156 with connection strength 311).The researchers initially focused on disability rehabilitation,then fo-cused on community-based rehabilitation and family rehabilitation,and gradually focused on the quality of life,activities of daily living,satisfaction,mental health,negative emotion and healthcare consortium in recent years. Conclusion The researches about multi-level rehabilitation service system are developing in China,focusing on commu-nity-based rehabilitation,stroke,family rehabilitation,rehabilitation nursing and quality of life.The cooperation among scholar groups need to be strengthened.Quality of life,activities of daily living,satisfaction,mental health,negative emotion and healthcare consortium may be the hotspots in the future.

Objective To investigate the role and regulatory mechanism of stress-inducing protein 1(SESN1)in liver gluconeogenesis of fasting mice.Methods RT-qPCR was used to detect mRNA expression of SESN1 in liver tissues of C57BL/6J mice and primary mouse hepatocytes treated with forskolin(Fsk)and dexamethasone(Dex).HepG2 cells were transfected with plasmids and the effects of SESN1 overexpression on mRNA expression of gluconeogenesis related genes PGC-1α,PEPCK and G6Pase was detected by RT-qPCR.The effect of SESN1 on the promoter activity of PGC-1α in HepG2 cells was studied using a dual luciferase reporter system.The effect of SESN1 on PGC-1α deacetylation was detected by overexpression of SESN1 and inhibition of SIRT1 expression.By knocking down SIRT1 expression,we detected whether it mediated the changes in mRNA levels of SESN1 in-duced gluconeogenesis related genes.Results The mRNA expression of SESN1 was significantly increased in liver tissues of starved C57BL/6J mice and in primary hepatocytes treated with Fsk and Dex(P<0.001).Over-expression of SESN1 in HepG2 cells promoted mRNA expression of PGC-1α,PEPCK and G6Pase(P<0.001)and promoter activity of PGC-1α(P<0.001).Over-expression of SESN1 decreased the acetylation level of PGC-1α in primary hepatocytes.Sirt family inhibitors NAM and shRNA adenovirus interfered with SIRT1 expression respective-ly,and antagonized the deacetylation effect of SESN1 on PGC-1α.The expression of PGC-1α,PEPCK and G6Pase induced by SIRT1 was also significantly impaired(P<0.000 1).Conclusions SESN1 regulates liver gluconeogene-sis in mice with a SIRT1-dependent mechanism.