OBJECTIVE To investigate the improvement mechanism of hyperoside （HYP） on non-alcoholic fatty liver disease （NAFLD）. METHODS Male C57BL/6 mice were randomly divided into normal （NFD） group， model （HFD） group and HYP group， with 8 mice in each group. Except for NFD group， the mice in other groups were fed with HF60 high-fat diet to establish NAFLD model； HYP group was simultaneously given HYP 100 mg/kg intragastrically every day， for 16 consecutive weeks. The body weight and liver weight of mice in each group were recorded 16 h after the last medication； the histopathological changes and lipid accumulation in the liver were observed， and the contents of triglyceride （TAG） in liver tissue and serum contents of TAG， aspartate transaminase （AST） and alanine transaminase （ALT） were measured； LC-MS/MS method was adopted to detect lipid changes in the liver tissue of mice for lipidomics analysis， and protein expressions of lipid synthesis-associated proteins peroxisome proliferator-activated receptor α （PPARα） were also tested. Human hepatocellular carcinoma cell line HepG2 was divided into normal control group， model group， HYP low-concentration group （50 μmol/L）， HYP high-concentration group （100 μmol/L）， HYP low-concentration+GW6471 （PPARαinhibitor） group， and HYP high-concentration+GW6471 group. Except for normal control group， the remaining cells were induced with oleic acid and palmitic acid to establish a high-fat cell model. The accumulation of lipid droplets in each group of cells was observed， and the TAG content was detected. RESULTS Compared with HFD group， HYP group exhibited significant reductions in liver fat vacuoles， lipid accumulation， liver weight， and TAG content in liver tissue， as well as serum contents of ALT， AST and TAG （P＜0.05）. Additionally， the expression of PPARα protein in liver tissue was significantly increased （P＜0.05）， and the pathological morphological changes associated with NAFLD were alleviated. Lipidomic analysis revealed that HYP significantly reduced the levels of TAG， diacylglycerol and other lipids in the liver. Compared with model group， cellular lipid droplet accumulation and TAG content decreased significantly in HYP low- and high-concentration groups （P＜0.05）； GW6471 could significantly reverse the improvement effect of HYP on above indicators （P＜0.05）. CONCLUSIONS HYP can effectively ameliorate NAFLD induced by a high-fat diet in mice， and the mechanism may be related to the activation of PPARα to regulate hepatic lipid synthesis.

Objective To observe the clinical effects of the stereotaxic oblique-pulling manipulation under different mechanical parameters in the treatment of patients with lumbar disc herniation,and to explore the muscle-relaxing effects of the stereotaxic oblique-pulling manipulation and the traditional lumbar oblique-pulling manipula-tion in the treatment of lumbar disc herniation under the optimal mechanical parameters.Methods Using a three-factor,three-level orthogonal test method,27 LDH patients included in this study were randomly divided into 9 parameter groups,with 3 patients in each group,and were treated with different parameters of the stereotactic angled wrench method.3 factors were set up for the pressing force,the number of times,and the treatment interval,and each factor consisted of 3 levels,i.e.,pressing force:300～400 N,400～500 N,and 500～600 N;the number of times pressed 3 levels were set up:6 times,9 times,12 times;3 levels of treatment interval:1 day interval,2 days interval,3 days interval.After screening the optimal mechanical parameters through VAS,ODI and FDD evaluation indexes,94 patients were included and randomly divided into two groups;the treatment group was stereotaxic oblique-pulling manipulation under the configuration of optimal mechanical parameters,and the control group was the traditional lumbar oblique-pulling manipulation,and the changes of patients'VAS and ODI scores as well as the thickness of multifidus muscle and cross-sectional area before and after treatment were observed in the treatment of the two groups of patients.Through the comparison of lumbar multifidus muscle between healthy volunteers and patients with lumbar keyboard herniation,the characteristics of lumbar disc herniation multifidus muscle were clarified.The correlation between each observation index and parameter was analyzed by the statistical analysis software SPSS 26.0 to derive the optimal parameters for manipulative treatment.Results Orthogonal test analysis yielded that the order of influence on the efficacy was pressing force>treatment interval>pressing times,and the pressure interval with the best efficacy was:500～600 N,the number of times was 12 times,and the Treatment internal of 2 days.The degree of degeneration of lumbar multifidus muscle in patients with lumbar disc herniation was more obvious compared with that of healthy volunteers,and the difference was stati stically signifi-cant(P<0.05).Observed in both groups of patients with lumbar disc herniation after 6 weeks of treatment time,the VAS and ODI scores of both groups decreased significantly after treatment compared with those before treatment(P<0.05),with greater improvement in the treatment group.The results of the multifidus muscle showed that after treatment,the treatment group could significantly increase the resting thickness,contraction thickness,contraction rate and cross-sectional area of the multifidus muscle had significant changes(P<0.05),in which the contraction thickness,contraction rate before and after the treatment changes were more significant than the control group.Conclusions The stereotaxic oblique-pulling manipulation is effective in the treatment of lumbar disc herniation,in which the manipulation parameter pressure of 500～600 N,the number of presses 12 times,and the treatment interval of 2 days once for the treatment of lumbar disc herniation has better analgesia and improves the dysfunction effect.Compared with the traditional lumbar oblique-pulling manipulation,the stereotaxic oblique-pulling manipulation is better in improving the pain symptoms and dysfunction of patients with lumbar disc hernia-tion,as well as the resting thickness of the multifidus muscle,the contraction thickness,the contraction rate of change,and the cross-sectional area.

Objective To observe the clinical effects of the stereotaxic oblique-pulling manipulation under different mechanical parameters in the treatment of patients with lumbar disc herniation,and to explore the muscle-relaxing effects of the stereotaxic oblique-pulling manipulation and the traditional lumbar oblique-pulling manipula-tion in the treatment of lumbar disc herniation under the optimal mechanical parameters.Methods Using a three-factor,three-level orthogonal test method,27 LDH patients included in this study were randomly divided into 9 parameter groups,with 3 patients in each group,and were treated with different parameters of the stereotactic angled wrench method.3 factors were set up for the pressing force,the number of times,and the treatment interval,and each factor consisted of 3 levels,i.e.,pressing force:300～400 N,400～500 N,and 500～600 N;the number of times pressed 3 levels were set up:6 times,9 times,12 times;3 levels of treatment interval:1 day interval,2 days interval,3 days interval.After screening the optimal mechanical parameters through VAS,ODI and FDD evaluation indexes,94 patients were included and randomly divided into two groups;the treatment group was stereotaxic oblique-pulling manipulation under the configuration of optimal mechanical parameters,and the control group was the traditional lumbar oblique-pulling manipulation,and the changes of patients'VAS and ODI scores as well as the thickness of multifidus muscle and cross-sectional area before and after treatment were observed in the treatment of the two groups of patients.Through the comparison of lumbar multifidus muscle between healthy volunteers and patients with lumbar keyboard herniation,the characteristics of lumbar disc herniation multifidus muscle were clarified.The correlation between each observation index and parameter was analyzed by the statistical analysis software SPSS 26.0 to derive the optimal parameters for manipulative treatment.Results Orthogonal test analysis yielded that the order of influence on the efficacy was pressing force>treatment interval>pressing times,and the pressure interval with the best efficacy was:500～600 N,the number of times was 12 times,and the Treatment internal of 2 days.The degree of degeneration of lumbar multifidus muscle in patients with lumbar disc herniation was more obvious compared with that of healthy volunteers,and the difference was stati stically signifi-cant(P<0.05).Observed in both groups of patients with lumbar disc herniation after 6 weeks of treatment time,the VAS and ODI scores of both groups decreased significantly after treatment compared with those before treatment(P<0.05),with greater improvement in the treatment group.The results of the multifidus muscle showed that after treatment,the treatment group could significantly increase the resting thickness,contraction thickness,contraction rate and cross-sectional area of the multifidus muscle had significant changes(P<0.05),in which the contraction thickness,contraction rate before and after the treatment changes were more significant than the control group.Conclusions The stereotaxic oblique-pulling manipulation is effective in the treatment of lumbar disc herniation,in which the manipulation parameter pressure of 500～600 N,the number of presses 12 times,and the treatment interval of 2 days once for the treatment of lumbar disc herniation has better analgesia and improves the dysfunction effect.Compared with the traditional lumbar oblique-pulling manipulation,the stereotaxic oblique-pulling manipulation is better in improving the pain symptoms and dysfunction of patients with lumbar disc hernia-tion,as well as the resting thickness of the multifidus muscle,the contraction thickness,the contraction rate of change,and the cross-sectional area.

OBJECTIVE To evaluate the contents of characteristic components in Hugan qingzhi formula(HGQZ)decoction and formulated granules and the pharmacodynamic consistency of them on high-fat diet-induced non-alcoholic fatty liver disease(NAFLD)model mice,and explore their potential underlying mechanisms of action.METHODS Liquid chromatography-tandem mass spectrometry was used to analyze and compare the contents of six characteristic components in HGQZ decoction and formulated granules.Male C57BL/6 mice were randomly divided into normal control group,model group,HGQZ decoction low-dose and high-dose groups(13,26 g/kg,calculated by crude drugs),and HGQZ formulated granules low-dose and high-dose groups(13,26 g/kg,calculated by crude drugs),with 6 mice in each group.Except for the normal control group,which was fed a regular diet,the mice in the other groups were fed a high-fat diet for 20 weeks to establish the NAFLD model;at the same time,the mice in each group were gavaged with the corresponding drugs/water once.The fasting blood glucose(FBG)levels,glucose and insulin tolerance,body weight,liver index,white adipose tissue index,brown adipose tissue index,as well as lipid levels(total cholesterol,triglycerides)and liver function indicators(aspartate transaminase,alanine transaminase)were measured.Additionally,histopathological changes and lipid accumulation in liver tissues were observed.The serum samples of mice in the model group,HGQZ decoction high-dose group and HGQZ formulated granules high-dose group were taken for metabolomics analysis,and validation of the underlying mechanisms was conducted.RESULTS There were no statistically significant differences in the contents of ginsenoside Rb1,typhaneoside,isorhamnetin-3-O-neohesperidoside,hyperoside,nuciferine,and 23-acetylalismol B between HGQZ decoction and HGQZ formulated granules(P＞0.05).Compared with the model group,the hepatic histopathological changes in mice were alleviated in both the HGQZ decoction group and all dose groups of HGQZ formulated granules.Inflammatory cell infiltration and lipid vacuoles were reduced.Additionally,there was a general improvement in FBG levels,glucose tolerance,insulin tolerance,body weight,liver index,white/brown adipose tissue index,lipid levels,and liver function indicators(P＜0.05).However,no statistically significant differences were observed between these treatment groups(P＞0.05).There were 234 and 136 differentially expressed serum metabolites identified in the model group versus HGQZ decoction high-dose group,and model group versus HGQZ formulated granules high-dose group,respectively.After taking the intersection,65 common differentially expressed metabolites were obtained,which were enriched in metabolic pathways such as purine metabolism and tricarboxylic acid cycle metabolism.Among these,the content of citrate in the model group was significantly lower than that in both the HGQZ decoction group and HGQZ formulated granules high-dose group(P＜0.05).Both high-dose HGQZ decoction and formulated granules could significantly elevate the phosphorylation levels of AMP-activated protein kinase(AMPK)(P＜0.05).CONCLUSIONS HGQZ decoction and formulated granules contain comparable amounts of characteristic components,and both exhibit equivalent efficacy on NAFLD model mice.The anti-NAFLD effects of HGQZ are associated with the activation of the AMPK energy metabolism pathway.

OBJECTIVE To study the effects of bergapten in the treatment of liver fibrosis and its mechanism based on serum metabolomics. METHODS Forty mice were divided into normal control group （0.5% carboxymethyl cellulose sodium solution）， model group （0.5% carboxymethyl cellulose sodium solution）， and BP low-dose and high-dose groups （50， 100 mg/kg）， with 10 mice in each group. Except for the normal control group， the other three groups were all treated with carbon tetrachloride to induce liver fibrosis model； they were given relevant medicine/solution intragastrically， once a day， for consecutive 8 weeks. After the last medication， the levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum were detected， and liver pathological changes were observed； the expressions of α-smooth muscle actin （α-SMA） and Collagen Ⅰ were detected in liver tissue； the serum of the mice was collected for metabolomics analysis. RESULTS Compared with the model group， serum levels of ALT and AST and protein expressions of α-SMA and Collagen Ⅰ in liver tissue were decreased significantly in BP high-dose and low-dose groups （P＜0.05）， while liver fibrosis was improved significantly. Meanwhile， metabolomics analyses showed that there were a total of 175 serum differential metabolites in the BP high-dose group and model group， of which 18 substances were upregulated and 157 substances were downregulated； the main metabolic pathways involved in bergapten intervention were pyrimidine metabolism， butanoate metabolism， fatty acid synthesis， tyrosine metabolism， β-alanine metabolism， nicotinic acid and nicotinamide metabolism， glutathione metabolism， etc. CONCLUSIONS BP is effective in the treatment of liver fibrosis by regulating pyrimidine metabolism， butanoate metabolism， glutathione metabolism and so on in rats with liver fibrosis.

OBJECTIVE To study the effects of isoliquiritigenin （ISL） regulating gut microbiota and repairing gut barrier function in model mice with non-alcoholic fatty liver disease （NAFLD）， and to clarify its mechanism for improving NAFLD. METHODS Thirty male C57BL/6J mice were randomly divided into the normal （ultrapure water）， model group （ultrapure water）， ISL group （100 mg/kg）， with 10 mice in each group. Model group and ISL group were fed with high-fat diet for 19 weeks to establish NAFLD model； at the same time， the mice were given relevant medicine/ultrapure water intragastrically. The changes of body weight in mice were recorded， and liver index， white fat index and brown fat index were calculated. The pathological changes of liver tissue and colon tissue as well as lipid accumulation were observed in mice. The levels of total cholesterol （TC）， triglyceride （TG）， aspartate aminotransferase （AST） and alanine aminotransferase （ALT） E-mail：xiangshj3@mail.sysu.edu.cn in serum or liver were measured； the serum levels of interleukin-6 （IL-6）， IL-1β and tumor necrosis factor-α （TNF-α） and the levels of IL-6， IL-1β and TNF-α mRNA expression in liver tissue were detected. Fecal samples underwent 16S rDNA sequencing analysis， and the effects of ISL on gut microbiota structure of mice were investigated. The expressions of gut mucosal barrier-related proteins （Claudin-4， Occludin and ZO-1） were determined in the colon tissue of mice. RESULTS Compared with model group， the body weight， liver index， the levels of TC in liver tissue and serum， the levels of AST and ALT in serum， the levels of IL-6， IL-1β and TNF-α in serum， and the mRNA expression of TNF-α in liver tissue were all decreased significantly in ISL group， while brown fat index was increased significantly. The inflammation and damage of liver tissue were significantly improved， and the NAFLD activity score and the proportion of lipid staining area were significantly reduced （P＜0.05）. ISL could significantly up-regulate the relative abundance of beneficial microbiota （norank_f_Muribaculaceae， Odoribacter， Ruminiclostridium， etc.） and the expressions of intestinal barrier function- related proteins， but could significantly down-regulate the relative abundance of harmful bacteria （Desulfovibrio， norank_f_Lachnospiraceae， unclassified_p_Firmicutes）， and could repair intestinal barrier. CONCLUSIONS ISL could significantly delay the progress of NAFLD， the mechanism of which may be associated with regulating gut microbiota and improving gut barrier function.

Objective:To explore the relationship between serum anti-Müllerian hormone (AMH) level and related clinical factors in healthy females, and establish and validate equation of correlation between age and serum AMH level for healthy females.Methods:From March 2015 to December 2016, a total of 602 females who measured serum AMH level in Department of Nuclear Medicine, the Second Affiliated Hospital of Soochow University were retrospectively enrolled. All cases had relatively complete clinical data, and were divided into healthy group (484 cases, 20-52 years) and case group (118 cases, 20-42 years; patients with menstrual disorders). Relationships between serum AMH level and estradiol (E2), tesosterone (T), follicle stimulating hormone (FSH), luetinizing hormone (LH), body mass index (BMI) of healthy group were analyzed by Spearman rank correlation. Kruskal-Wallis rank sum test was used to analyze the relationship between history of gestation and serum AMH level. Serum AMH level of health group was processed to establish predictive equation for serum AMH level. Internal ( n=27) and external ( n=37) validation group were chosen from healthy females with serum AMH level measured to validate the equation, and signed rank test was used to analyze the data. Difference between serum AMH level in case group and healthy group with corresponding age was explored by independent-sample t test. Results:Serum AMH levels were positively correlated with E2 and T ( rs values: 0.263, 0.334, both P<0.001), and negatively correlated with FSH, LH, BMI ( rs values: from -0.515 to -0.110, all P<0.005). Predictive equation was established as LogAMH=-1.208+ 0.1×age-0.000 042×age 3 ( R2=0.735, P<0.001). No statistically significant difference was found between real serum AMH levels and calculated serum AMH levels in the internal and external validation groups ( z values: -1.62 and -1.52, both P>0.05). Females in case group ( n=118) and control group ( n=446) were divided into two sub-groups respectively (<35 years and ≥35 years), and serum AMH levels of case group were lower than those of control group with corresponding age ( t values: 18.64, 11.70, both P<0.001). Conclusions:In healthy females, serum AMH level is related to some clinical data. The equation between serum AMH level and age established in the study may provide reference for clinical diagnosis and treatment.

Sepsis is a critical illness with high morbidity and mortality. Anaerobic glycolysis plays an important role in the pathogenesis of sepsis. Pyruvate dehydrogenase complex (PDHC) serves as a key regulator during sepsis. With PDHC dephosphorylation and deacetylation, PDHC activity is upregulated, allowing pyruvate translocate to mitochondria in aerobic condition, preceding the production of acetyl-CoA to accelerate aerobic oxidation. Activation of PDHC improves the prognosis of sepsis through regulating the balance of lactate, release of inflammatory factors and energy metabolism. A variety of remedies can improve the prognosis of patients with sepsis by up-regulating the activity of PDHC, including dichloroacetate (DCA), vitamin B1, milrinone, tumor necrosis factor binding protein, and ciprofloxacin.This article reviews the role and the regulatory mechanism of PDHC and signal pathway in the sepsis metabolism, in order to innovate treatment for sepsis and multiple organ dysfunction.

Objective:To explore the clinical effect of the simultaneous innervated "Bi-system bone flap" on preventing postoperative spontaneous resorption of the bone grafts and recovering lip sensation after reconstructing mandibular defects.Methods:Patients with segmental mandibular defects from the Department of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People’s Hospital were prospectively selected. Following the screening, they were randomly divided into an innervated group and a control group according to the random number table. When the free vascularized iliac bone flap was used to repair the mandibular defect, the ilioinguinal nerve was chosen to innervate a composite tissue flap containing one pedicle (deep circumflex iliac artery), double islands (an internal oblique muscle flap and an iliac bone flap) and one nerve (ilioinguinal nerve). We anastomosed the ilioinguinal nerve with the inferior alveolar nerve and the mental nerve in the innervated group. In the control group, no nerve was involved in the composite tissue flap which contained one pedicle (deep circumflex iliac artery) and double islands (internal oblique muscle flap and iliac bone flap). CT value(Hu) decrease rate, width and height of iliac bone flap 6 months after the operation were used to evaluate the postoperative resorption. The algesia examination, two-point discrimination test and current perception threshold (CPT) test of sensory nerves were used to evaluate the recovery of the lower lip sensation. P value less than 0.05 in independent-samples t test meant the statistically significant difference. Results:Eight patients between 17-38 years old were included with an averaged age of 29.5 years, and the range of mandibular defects was 5-9 cm. There were 4 cases in the innervated group and 4 cases in the control group. All the iliac bone flaps survived. The appearance was satisfactory, and no severe complications were found in the donor and recipient sites. In six-month follow-up, the CT value decrease rate of the bone grafts was (3.13±1.21)% in the innervated group, less than that (20.32±5.23)% in the control group, and the difference was statistically significant ( t=-6.401, P=0.006). Few changes of width and height of the bone grafts were found 6 months after surgery in both groups, and the difference was not statistically significant ( P>0.05). The sensation of the lower lip in the operation area was recovered in the innervated group to some extent, and no obvious pain was showed in the control group. In the two-point discrimination test, it was more than 20 mm in the affected side of the control group, while it was less than 20mm in the innervated group. In the healthy side of the two groups, it was less than 14 mm. The results of the quantitative sensory examination in affected lower lip by CPT test showed that two cases in the innervated group were mild sensory dysfunction, one slight sensory dysfunction and one moderate sensory dysfunction, while all cases in the innervated group were severe sensory dysfunction. The sensory dysfunction of the healthy side was milder than that of the affected side. Conclusions:The innervated "Bi-system" DCIA flap can prevent postoperative osteoporosis of the bone grafts and recover the sensation of the lower lip following mandibular reconstruction, improving the quality of mandibular defect reconstruction.

Objective:To explore the clinical effect of the simultaneous innervated "Bi-system bone flap" on preventing postoperative spontaneous resorption of the bone grafts and recovering lip sensation after reconstructing mandibular defects.Methods:Patients with segmental mandibular defects from the Department of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People’s Hospital were prospectively selected. Following the screening, they were randomly divided into an innervated group and a control group according to the random number table. When the free vascularized iliac bone flap was used to repair the mandibular defect, the ilioinguinal nerve was chosen to innervate a composite tissue flap containing one pedicle (deep circumflex iliac artery), double islands (an internal oblique muscle flap and an iliac bone flap) and one nerve (ilioinguinal nerve). We anastomosed the ilioinguinal nerve with the inferior alveolar nerve and the mental nerve in the innervated group. In the control group, no nerve was involved in the composite tissue flap which contained one pedicle (deep circumflex iliac artery) and double islands (internal oblique muscle flap and iliac bone flap). CT value(Hu) decrease rate, width and height of iliac bone flap 6 months after the operation were used to evaluate the postoperative resorption. The algesia examination, two-point discrimination test and current perception threshold (CPT) test of sensory nerves were used to evaluate the recovery of the lower lip sensation. P value less than 0.05 in independent-samples t test meant the statistically significant difference. Results:Eight patients between 17-38 years old were included with an averaged age of 29.5 years, and the range of mandibular defects was 5-9 cm. There were 4 cases in the innervated group and 4 cases in the control group. All the iliac bone flaps survived. The appearance was satisfactory, and no severe complications were found in the donor and recipient sites. In six-month follow-up, the CT value decrease rate of the bone grafts was (3.13±1.21)% in the innervated group, less than that (20.32±5.23)% in the control group, and the difference was statistically significant ( t=-6.401, P=0.006). Few changes of width and height of the bone grafts were found 6 months after surgery in both groups, and the difference was not statistically significant ( P>0.05). The sensation of the lower lip in the operation area was recovered in the innervated group to some extent, and no obvious pain was showed in the control group. In the two-point discrimination test, it was more than 20 mm in the affected side of the control group, while it was less than 20mm in the innervated group. In the healthy side of the two groups, it was less than 14 mm. The results of the quantitative sensory examination in affected lower lip by CPT test showed that two cases in the innervated group were mild sensory dysfunction, one slight sensory dysfunction and one moderate sensory dysfunction, while all cases in the innervated group were severe sensory dysfunction. The sensory dysfunction of the healthy side was milder than that of the affected side. Conclusions:The innervated "Bi-system" DCIA flap can prevent postoperative osteoporosis of the bone grafts and recover the sensation of the lower lip following mandibular reconstruction, improving the quality of mandibular defect reconstruction.