Osteoporosis is a common bone disease， whose incidence is still on the rise， posing great challenges to patients and society. This review mainly studies the pathogenesis of osteoporosis from the aspects of oxidative stress， inflammatory response， and glucolipotoxicity-induced injury and clarifies the efficacy and mechanism of some active ingredients of traditional Chinese medicine against osteoporosis through the integration of in vitro and in vivo experiments. The experimental results suggest that some active ingredients can improve bone resorption markers and maintain bone homeostasis by modulating inflammation， oxidative stress， etc. These active ingredients regulate osteoporosis through the receptor activator of nuclear transcription factor-κB （NF-κB） ligand （RANKL） pathway， osteoprotegerin （OPG） pathway， Wnt/β-catenin pathway， NF-κB pathway， mitogen-activated protein kinase （MAPK） pathway， adenosine monophosphate （AMP）-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） pathway， and oxidative stress pathway. This review provides ideas for the progress of the prevention and treatment of osteoporosis with the active ingredients of traditional Chinese medicine， aiming to provide new potential lead compounds and reference for the development of innovative drugs and clinical therapy for the treatment of osteoporosis.

OBJECTIVE To explore the effect and mechanism of Zhiqiao gancao decoction （ZQGCD） on pathological angiogenesis of degenerative intervertebral disc. METHODS The rats were randomly divided into sham operation group （normal saline）， model group （normal saline）， hypoxia inducible factor-1α （HIF-1α） inhibitor （YC-1） group [2 mg/（kg·d）， tail vein injection]， and ZQGCD low-dose， medium-dose and high-dose groups [3.06， 6.12， 12.24 g/（kg·d）]， with 8 rats in each group. Except for sham operation group， lumbar disc degeneration model of rat was constructed in all other groups. After modeling， they were given relevant medicine once a day， for consecutive 3 weeks. After the last medication， pathological changes and angiogenesis of the intervertebral disc tissue in rats were observed； the levels of inflammatory factors [interleukin-1β （IL-1β）， IL-6， tumor necrosis factor-α （TNF-α）] and the expressions of angiogenesis-related proteins [HIF-1α， vascular endothelial growth factor （VEGF）， VEGF receptor 2 （VEGFR2）， angiotensin 1（Ang 1）， Ang 2] in the com intervertebral disc tissue in rats were all determined. In cell experiment， the primary nucleus pulposus cells were isolated and cultured from rats， and cellular degeneration was induced using 50 ng/mL TNF-α. The cells were divided into blank control group （10% blank control serum）， TNF-α group （10% blank control serum）， YC-1 group （10% blank control serum+0.2 mmol/L YC-1）， and 5%， 10%， 15% drug-containing serum group （5%， 10%， 15% drug-containing serum）. After 24 hours of intervention， the nucleus pulposus cells were co-cultured with HUVEC. The expressions of Collagen Ⅱ， matrix metalloproteinase-3 （MMP-3） in nucleus pulposus cells were detected. HUVEC proliferation， migration and tube forming ability were detected， and the expression levels of the HIF-1α/VEGF/Ang signal axis and angiogenesis- related proteins （add MMP-2， MMP-9） in HUVEC were detected. RESULTS Animal experiments had shown that compared with model group， the positive expression of CD31 in the intervertebral disc tissues of rats in each drug group was down-regulated （P＜ 0.05）， the levels of inflammatory factors and angiogenesis-related proteins were decreased significantly （P＜0.05）， and the pathological changes in the intervertebral disc were alleviated. Cell experiments had shown that compared with TNF-α group， the expression of Collagen Ⅱ in nucleus pulposus cells of all drug groups was significantly up-regulated （P＜0.05）， and the expression of MMP-3 was significantly down-regulated （P＜0.05）； the proliferation， migration and tubulogenesis of HUVEC were significantly weakened （P＜0.05）. The mRNA and protein expressions of HIF-1α， VEGF， Ang 2 as well as the expression of angiogenesis-related proteins （except for the expression of Ang 2 mRNA and HIF-1α， VEGFR2， Ang 2 protein in 5% drug- containing serum group） were significantly down-regulated （P＜0.05）. CONCLUSIONS ZQGCD may inhibit the HIF-1α/VEGF/ Ang signal axis to weaken the angiogenic ability of vascular endothelial cells， improve pathological angiogenesis in the intervertebral disc， and delay the degeneration of the intervertebral disc.

OBJECTIVES: To explore the molecular mechanism of Jiangzhi Huaban Decoction (JZHBD) for improving atherosclerosis through the "qi meridian-blood channels" pathway. METHODS: ApoE^-/- mouse models of atherosclerosis were established by high-fat diet feeding for 8 weeks, with C57BL/6 mice on a normal diet as the controls. Forty ApoE^-/- mouse models were randomized into model group, low-, medium-, and high-dose JZHBD treatment groups, and atorvastatin treatment group (n=8) for their respective treatments for 8 weeks. The changes in body weight and overall condition of the mice were monitored weekly. After the treatments, serum levels of TC, TG, HDL-C, LDL-C, TBA, ALT, and AST of the mice were measured, pathological changes in the liver and aortic root plaques were examined with HE staining, and lipid accumulation in the liver and aortic wall was assessed using Oil Red O staining. The core molecular mechanism was studied through transcriptomics, and the expressions of the key pathway proteins were confirmed using Western blotting and immunohistochemistry. RESULTS: Treatment with JZHBD significantly reduced blood lipid and total bile acid levels, improved liver function and hepatic steatosis, and decreased aortic lipid deposition and plaque area in the mouse models of atherosclerosis. Transcriptomic analysis suggested that the therapeutic mechanism of JZHBD involved reverse cholesterol transport, PPAR signaling, and the inflammatory pathways. In atherosclerotic mice, JZHBD treatment obviously up-regulated hepatic expressions of PPARγ, LXRα, ABCA1, ABCG1, and CYP7A1, down-regulated hepatic expressions of p-p65/p65, IL-6, IL1β in the liver, increased ABCG5 and ABCG8 expressions in the intestines, and decreased ICAM-1 and VCAM-1 expressions in the aortic plaques. CONCLUSIONS JZHBD improves atherosclerotic vascular damage and plaque formation possibly by regulating hepatic reverse cholesterol transport and inflammation via modulating the hepatic PPARγ/LXRα/NF-κB signaling pathway.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred C57BL ; Plaque, Atherosclerotic/metabolism* ; Liver/metabolism* ; Mice ; Atherosclerosis/metabolism* ; Cholesterol/metabolism* ; PPAR gamma/metabolism* ; Male ; Diet, High-Fat ; Biological Transport

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective To investigate the application value of quantitative parameters MRFDGmax and SUVmax in the stages of hepatitis,liver fibrosis and cirrhosis in rats by whole-body dynamic 18 F-FDG PET/CT Patlak imaging.Methods Twenty-four SD rats were randomly divided into four groups of six rats each,which were the normal group,hepatitis group,liver fibrosis group and cirrhosis group.According to the experimental grouping,rats in each group were induced by the CC14 oil solution complex method.Whole-body dynamic 18 F-FDG PET/CT patlak imaging was performed on each group of rats separately at the completion of induction.After the imaging was com-pleted,the MRFDGmax,SUVmax and CT values of the livers of each group were analyzed;subsequently,the serum of rats in each group was extracted for the detection of liver function indexes(AST,ALT and ALP),and HE staining was performed on the livers of rats in the normal,hepatitis and cirrhosis groups,and Masson staining was performed on those in the liver fibrosis group;the α-SMA expression in the liver tissues of each group was analyzed by immu-nohistochemical method.The data were analyzed by one-way ANOVA,two independent samples t-test and Pearson correlation analysis.Results MRFDGmax,SUVmax values were statistically significant differences among normal,hep-atitis,liver fibrosis and cirrhosis groups(F=84.54,38.35,P＜0.001).The difference in CT values between liver fibrosis and cirrhosis groups was not statistically significant(t=-0.407,P=0.693),and the difference was statistically significant when compared between the rest of the groups(F=112.25,P＜0.001).Compared with the normal group,AST,ALT and ALP of the experimental group showed a staged increase,and the differences were statistically significant(F=93.32,64.63,145.03,P＜0.001).HE staining showed that hepatocytes of the normal group were neatly arranged and structurally intact;a large number of inflammatory cells infiltrated the hepa-titis group with steatosis;pseudo lobe formation was observed in the cirrhosis group.Masson staining of the liver fi-brosis group showed collagen fiber proliferation and thickening of the peritoneum.Immunohistochemistry test results showed that α-SMA expression increased in hepatitis group,liver fibrosis group and cirrhosis group,with a staged increase,and the difference was statistically significant(F=80.57,P＜0.001).Correlation analysis showed a positive correlation between SUVmax and MRFDGmax(r=0.967,P＜0.01).α-SMA was positively correlated with AST,ALT and ALP in the hepatitis,liver fibrosis and cirrhosis groups,respectively(r=0.924,0.756,0.934,P＜0.01).Conclusion Whole-body dynamic 18F-FDG PET/CT Patlak imaging has application value in monitoring hepatitis,liver fibrosis and cirrhosis stages through quantitative parameters MRFDGmax and SUVmax changes.

BACKGROUND:MicroRNA(miRNA)levels are closely related to cell apoptosis and proliferation,extracellular matrix metabolism and inflammatory response in intervertebral disc cells.However,the specific role of miR-142-3p in lumbar intervertebral disc degeneration remains unclear. OBJECTIVE:To investigate the correlation between the expression of miRNA-142-3p,mixed lineage kinase 3 and interleukin-1β in nucleus pulposus tissue and degree of human lumbar intervertebral disc degeneration. METHODS:A total of 82 patients with lumbar intervertebral disc degenerative diseases in Suzhou Ninth People's Hospital from January 2020 to March 2022 were collected as the study subjects,all of whom underwent MRI examination before operation.According to the Videman classification,the patients were divided into mild degeneration group(n=36),moderate degeneration group(n=26)and severe degeneration group(n=20).Eighty-two specimens of the nucleus pulposus were obtained.The mRNA expression of miRNA-142-3p as well as the mRNA and protein expression of mixed lineage kinase 3,interleukin-1β,type I collagen,type II collagen in nucleus pulposus tissue were detected by qPCR and western blot assay.The correlation between the degree of human lumbar intervertebral disc degeneration and the expression levels of miRNA-142-3p,mixed lineage kinase 3,and interleukin-1β was also assessed using the Spearman correlation coefficient method.Thirty adult Sprague-Dawley rats were divided into sham-operated group(executed after puncturing skin and muscle only),mild degeneration group(executed 1 week after puncturing Co7/8 segments)and severe degeneration group(executed 2 weeks after puncturing Co7/8 segments),with 10 rats in each group.After that,we detected the protein expression of mixed lineage kinase 3 and interleukin-1β as well as the gene expression of miRNA-142-3p,mixed lineage kinase 3 and interleukin-1β in the nucleus pulposus tissue. RESULTS AND CONCLUSION:In human nucleus pulposus tissue,the miRNA-142-3p expression ranked from high to low as follows:mild degeneration group>moderate degeneration group>severe degeneration group(P<0.05);the gene and protein expression of mixed lineage kinase 3 and interleukin-1β from low to high was as follows:mild degeneration groupmoderate degeneration group>severe degeneration group(P<0.05).Spearman correlation analysis showed that the degree of disc degeneration was negatively correlated with miRNA-142-3p expression(P<0.05)and positively correlated with mixed lineage kinase 3 and interleukin-1β expression(P<0.05).In rat nucleus pulposus tissue,compared with the sham-operated group,the expression of mixed lineage kinase 3 and interleukin-1β gene and protein was elevated in the mild degeneration group(P<0.05)while miRNA-142-3p expression was decreased(P<0.05);compared with the mild degeneration group,the expression of mixed lineage kinase 3 and interleukin-1β gene and protein was increased in the severe degeneration group(P<0.05)while miRNA-142-3p expression was decreased(P<0.05).To conclude,the degree of human lumbar intervertebral disc degeneration is negatively correlated with miRNA-142-3p expression and positively correlated with mixed lineage kinase 3 and interleukin-1β expression in nucleus pulposus tissue.

A combined epidemic prediction method based on multi-source data fusion is presented to address the common problems of low accuracy,weak generalization,single structure,poor nonlinear processing ability,and long prediction time in traditional epidemic prediction models.The collected multi-source epidemic data are normalized and subjected to feature selection using principal component analysis.An ARIMA-GM-BPNN model for pandemic prediction is constructed by combining ARIMA model,grey GM model and BPNN.The fitting values of the first two prediction models are used as inputs to BPNN for model training.After sufficiently integrating the data and combining the advantages of different prediction models,the optimal combined model is obtained and used for forecasting the incidence and trend of epidemics.Experimental results show that the combined model exhibits excellent fitting performance,with predicted incidences and trends consistent with the real conditions.The proposed approach improves prediction accuracy and generalization capabilities,and it can provide reliable data support for epidemic prediction and control.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective : To analyze the difference of urinary iodine level in Hashimoto thyroiditis ( HT) patients， and to explore the possible relationship between urinary iodine level and HT under different iodine nutritional sta- tus，so as to provide some references for reasonable iodine intake in HT patients． Methods : A total of 101 hospi- talized HT patients were selected as HT group and divided into 3 groups according to thyroid function : HT group with hyperthyroidism (41 cases) ．There were 25 cases in HT group with normal thyroid function．There were 35 cases in HT combined with hypothyroidism group．In addition，30 healthy subjects were selected as control group. Serum levels of thyroid stimulating hormone(TSH) ，triiodothyronine(T3 ) ，thyroxine (T4 ) ，thyroid peroxidase an- tibody (TPOAb) and thyroglobulin antibody (ATG) were detected by chemiluminescence assay．The size and mor- phological structure of thyroid organs were examined by ultrasonography．Urinary iodine was determined by catalytic spectrophotometry with arsenic and cerium．The nutritional status of iodine was classified into iodine deficiency ( < 100 μg/ L) ，iodine adequacy( 100 －199 μg/ L) ，iodine adequacy (200 －299 μg/ L) and iodine excess ( ≥ 300 μg/ L) ．Non-parametric test was used to compare urinary iodine level between HT group and control group，one- way ANOVA and t test were used to compare urinary iodine level between HT group and control group ，and Spearman correlation analysis was used to compare the correlation between urinary iodine level and T3 ，T4 ，TSH， ATG and TPOAb under different iodine nutrition status. Results : Compared with control group，ATG and TPOAb levels in HT group increased (P＜0. 001) ，and urinary iodine levels increased (P＜0. 05) ，with statistical signifi- cance．Compared with the control group in different thyroid function states，only the HT group with hypothyroidism increased the urinary iodine level (P＜0. 01) ，and the difference was statistically significant．Spearman correlation analysis showed that urine iodine level was positively correlated with ATG and TPOAb levels in iodine excess condi- tion (P＜0. 05) ，and urine iodine level was positively correlated with TSH level in iodine sufficient condition and iodine excess condition in HT patients (P＜0. 05) ． Conclusion The urinary iodine level of HT patients was high- er than that of normal people．When the urinary iodine level of residents is ≥ 300 μg/ L，iodine intake is prone to HT．When the urinary iodine level of HT patients is ≥ 200 μg/ L，iodine consumption is prone to hypothyroidism， and iodine intake should be limited.