ObjectiveTo investigate the mechanisms by which Bushen Tongluo Jiangzhuo prescription improves renal fibrosis in rats with chronic kidney disease （CKD） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsSeventy specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a control group （n=15） and a modeling group （n=55）. Rats in the modeling group were administered a 2.5% adenine suspension at a dose of 200 mg·kg^-1·d^-1 by gavage for 4 weeks to establish a CKD model. Successfully modeled rats were randomly divided into a model group， an irbesartan group （20.25 mg·kg^-1·d^-1）， and Bushen Tongluo Jiangzhuo prescription low-， medium-， and high-dose groups （5.82， 11.64， and 23.28 g·kg^-1·d^-1， respectively）， with 10 rats in each group. Each group was administered an equal volume of physiological saline， the corresponding concentration of irbesartan， or Bushen Tongluo Jiangzhuo prescription by gavage for 12 weeks. Body weight and renal function indices were dynamically monitored. Serum creatinine （SCr）， blood urea nitrogen （BUN）， urine albumin-to-creatinine ratio （ACR）， 24-hour urinary total protein （24 hUTP）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） levels were measured using an automatic biochemical analyzer. Renal histopathological changes were observed by hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry （IHC） was used to detect the expression of PI3K， Akt， phosphorylated Akt （p-Akt）， and mTOR in renal tissues. Western blot was performed to assess the protein expression of PI3K， p-Akt， Akt， phosphorylated mTOR （p-mTOR）， and mTOR in renal tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression levels of PI3K， Akt， and mTOR in renal tissues. ResultsCompared with the model group， rats in the irbesartan group and the low-， medium-， and high-dose Bushen Tongluo Jiangzhuo prescription groups showed significantly decreased levels of SCr， BUN， ACR， 24 hUTP， IL-1β， IL-6， and TNF-α （P<0.01）. AST levels were significantly increased （P<0.01）， while no significant difference was observed in ALT levels. Histopathological examination revealed that， compared with the model group， renal tubular epithelial cell edema and necrosis and Bowman's capsule dilation were alleviated， inflammatory cell infiltration was reduced， and interstitial and glomerular fibrosis was markedly improved in all treatment groups， with the most pronounced effect observed in the high-dose Bushen Tongluo Jiangzhuo prescription group. Real-time PCR results showed that mRNA expression levels of PI3K， Akt， and mTOR were significantly downregulated in the high-dose group （P<0.01）. IHC results demonstrated that PI3K and p-Akt expression levels in renal tissues were significantly decreased in the high-dose group （P<0.01）. Western blot analysis further confirmed that the expression levels of PI3K， p-Akt/Akt， and p-mTOR/mTOR were significantly reduced in the high-dose group （P<0.01）. ConclusionBushen Tongluo Jiangzhuo prescription improves renal function indices in CKD rats， reduces collagen deposition in renal tissues， and decreases serum inflammatory factor levels. Its protective effect on renal function may be achieved by activating autophagy through downregulation of the PI3K/Akt/mTOR signaling pathway， thereby alleviating renal fibrosis.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

ObjectiveTo investigate the molecular mechanism by which the Bushen Kaixuan Tongluo prescription exerts a renal protective effect in mice with diabetic kidney disease （DKD） by regulating the cyclic adenosine monophosphate （cAMP） signaling pathway. MethodsThirty specific pathogen-free （SPF） male db/db mice were adaptively fed for three weeks. Mice with a random tail vein blood glucose level ≥ 11.1 mmol·L^-1 and urinary albumin-creatinine ratio （ACR） ≥ 30 mg·g^-1 were considered successfully modeled. The successfully modeled mice were randomly divided into five groups with six mice in each group： the model group， the low-， medium-， and high-dose Bushen Kaixuan Tongluo prescription groups （administered at doses of 7， 14， 28 g·kg^-1·d^-1 respectively）， and the positive drug irbesartan group （administered at a dose of 20 mg·kg^-1·d^-1）. Additionally， six db/m mice were selected as the blank group. Mice in each group were given intragastric administration of the Bushen Kaixuan Tongluo prescription at the corresponding concentrations， irbesartan， or an equal volume of pure water， and the intervention lasted for 12 weeks. During the experiment， the general conditions， body weight changes， and renal function indicators of the mice were dynamically monitored. After the intervention， a blood glucose meter was used to measure the fasting blood glucose （FBG） of the mice. An automatic biochemical analyzer was employed to detect the levels of serum creatinine （SCr）， blood urea nitrogen （BUN）， urinary microalbumin （uALB）， ACR， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglycerides （TG）， leptin （LEP）， glycosylated serum protein （GSP）， and insulin （INS） in the mice. Renal tissues were collected for hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson's trichrome staining to observe the histopathological changes. Immunohistochemistry （IHC） was used to detect the expressions of protein kinase A （PKA） and cAMP response element-binding protein （CREB） in the mice. Western blot analysis was performed to determine the expression levels of PKA， phosphorylated protein kinase A （p-PKA）， CREB， phosphorylated cAMP response element-binding protein （p-CREB）， and B-cell lymphoma-2 （Bcl-2） proteins in the renal tissues of the mice. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of PKA， CREB， and Bcl-2 in the renal tissues of the mice. ResultsCompared with the blank group， the mice in the model group showed listlessness， decreased activity， and a significant increase in body weight （P<0.01）. Biochemical indicators revealed that the levels of BUN， uALB， ACR， AST， ALT， TC， TG， FBG， LEP， GSP， and INS were significantly increased （P<0.01）， while SCr showed an increasing trend with no statistically significant difference. Compared with the model group， the mice in the Bushen Kaixuan Tongluo prescription intervention groups had improved general conditions and a decreasing trend in body weight. Biochemical indicators showed that the levels of BUN， uALB， ACR， TC， GSP， and INS were significantly decreased （P<0.05）， while SCr， AST， ALT， TG， and LEP showed a decreasing trend with no statistically significant difference. Renal histopathological analysis showed that the model group exhibited typical DKD pathological features such as thickening of the glomerular basement membrane， expansion of the mesangial matrix， and deposition of collagen fibers in the renal tubulointerstitium， and all treatment groups could alleviate the above pathological damages. The IHC results showed that compared with the blank group， the expression levels of p-PKA and p-CREB in the renal tissues of the model group were significantly decreased （P<0.01）. Compared with the model group， the expression level of p-PKA in the medium-dose Bushen Kaixuan Tongluo prescription group was significantly increased （P<0.01）， while the expression level of p-CREB showed an increasing trend with no statistically significant difference. Western blot results showed that compared with the blank group， the expression levels of p-PKA/PKA， p-CREB/CREB， and Bcl-2 in the model group were significantly decreased （P<0.05）. Compared with the model group， the expression levels of these proteins in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly increased （P<0.01）. Real-time PCR results showed that compared with the blank group， the mRNA expressions of PKA， CREB， and Bcl-2 in the model group were significantly down-regulated （P<0.05）. Compared with the model group， the mRNA expressions of these genes in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly up-regulated （P<0.05）. ConclusionThe Bushen Kaixuan Tongluo prescription can improve the liver and kidney functions of db/db mice， correct lipid metabolism disorders and glucose metabolism imbalance. Its renal protective effect is associated with up-regulating the cAMP signaling pathway to improve renal fibrosis and reduce the level of oxidative stress， thereby protecting renal function.

It is believed that there is a pathogenesis of yang deficiency in polycystic ovary syndrome （PCOS） infertility， and it is concluded that warm-yang method has a better effect in improving endometrial abnormality， enhancing the quality of follicles， correcting endocrine disorders， and resolving or alleviating clinical symptoms in PCOS infertility. Based on Yanghe Decoction （阳和汤）， a representative traditional Chinese medicine decoction for warming yang， Yanghe Xiaonang Decoction （阳和消囊汤） was formulated， combining with warm medicinals according to symptoms， and aerobic exercise was also advocated to help generate and develop yang qi， in order to provide ideas for clinical treatments.

ObjectiveTo observe the clinical efficacy and possible mechanisms of Xianglian Huazhuo Granules （香连化浊颗粒， XHG） in the treatment of chronic atrophic gastritis with intestinal metaplasia. MethodsA total of 140 patients with chronic atrophic gastritis and intestinal metaplasia were randomly divided into a treatment group and a control group， with 70 cases in each group. The treatment group received 12.5 g of XHG orally， twice daily. The control group received 12.5 g of placebo orally， twice daily. Both groups were treated for 6 months. The traditional Chinese medicine （TCM） symptom scores， pathological types， serum tumor markers of the digestive system， and serum bile acids （TBA）， interleukin-23 （IL-23）， and Dickkopf-related protein 1 （DKK-1） levels were observed before and after treatment. Safety indicators and adverse events were recorded. After treatment， TCM syndrome efficacy and pathological types were evaluated， and patients were followed up for 18 months with gastric endoscopy and pathological results， which were compared with the results after treatment finished. ResultsTwo patients dropped out in the control group， and a total of 168 cases were included in the final analysis， 70 in the treatment group and 68 in the control group. The treatment group showed a significant reduction in TCM symptom scores， serum TBA， IL-23， and DKK-1 levels， and a significant increase in alpha-fetoprotein （AFP）， carbohydrate antigen 125 （CA125）， carbohydrate antigen 199 （CA199） levels； in the control group， carcinoembryonic antigen （CEA）， CA125， CA199 levels significantly increased （P＜0.05 or P＜0.01）； and carbohydrate antigen 242 （CA242） level in both the treatment group and the control group decreased significantly （P＜0.01）. The treatment group had lower TCM symptom scores and lower levels of serum TBA， IL-23， and DKK-1 compared to the control group （P＜0.05）. The effective rate for TCM syndrome efficacy in the treatment group was 80.00% （56/70）， significantly higher than the 20.59% （14/68） in the control group （P < 0.05）. The effective rate for pathological classification in the treatment group was 72.73% （8/11） for mixed intestinal metaplasia， significantly better than 46.15% （6/13） in the control group （P＜0.05）. No adverse events were reported in either group. Among 40 patients who had a follow-up endoscopy after one year， 21 were from the treatment group， of whom 11 showed reduced intestinal metaplasia， 9 showed no significant changes， and 1 had worsened； while 19 patients in the control group had 4 with reduced intestinal metaplasia， 13 with no significant changes， and 2 with worsened conditions. No cancer was detected in either group. The treatment group showed significantly better improvement in intestinal metaplasia on follow-up gastric endoscopy pathology than the control group （P＜0.05）. ConclusionXHG can significantly improve the clinical symptoms in patients with chronic atrophic gastritis and intestinal metaplasia and reduce the degree of mixed intestinal metaplasia. The mechanism may involve lowering serum TBA， DKK-1， and IL-23 levles， thus delaying the progression from inflammation to cancer.

Coronary heart disease is a chronic and lifelong disease， which places a dual burden on the physiological and psychological well-being of patients， and can easily lead to psychological distress and affect their prognosis and quality of life. This article provides a systematic review， in which the current status， evaluation tools， influencing factors and intervention methods of psychological distress in patients with coronary heart disease are explored， aiming to provide key information beneficial for identifying and preventing psychological distress， and to improve the overall management and treatment effectiveness of coronary heart disease patients. In this paper， 18 articles were included， and the demographic， physiological， psychological and social factors affecting the psychological distress of patients with coronary heart disease were systematically analyzed， thus to provide a deeper understanding of psychological distress and offering references for formulating targeted intervention strategies.

BACKGROUND:Cervical disc herniation can cause pain in the neck and shoulder area,as well as radiating pain in the upper limbs.The incidence rate is increasing year by year and tends to affect younger individuals.Fully understanding the biomechanical characteristics of the cervical spine in adolescents is of great significance for preventing and delaying the onset of cervical disc herniation in this age group. OBJECTIVE:To reconstruct cervical spine models for both healthy adolescents and adolescent patients with cervical disc herniation utilizing finite element analysis techniques,to analyze the motion range of the C1-T1 cervical vertebrae as well as the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and the cartilage of the small joints. METHODS:A normal adolescent's cervical spine and an adolescent patient with cervical disc herniation were selected in this study.The continuous scan cervical spine CT raw image data were imported into Mimics 21.0 in DICOM format.The C1-T1 vertebrae were reconstructed separately.Subsequently,the established models were imported into the 3-Matic software for disc reconstruction.The perfected models were then imported into Hypermesh software for meshing of the vertebrae,nucleus pulposus,annulus fibrosus,and ligaments,creating valid geometric models.After assigning material properties,the final models were imported into ABAQUS software to observe the joint motion range of the C1-C7 cervical vertebrae segments under different conditions,and to analyze the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and small joint cartilage of each cervical spine segment. RESULTS AND CONCLUSION:(1)In six different conditions,the joint motion range of the C1 vertebra in the cervical spine models of both normal adolescent and adolescent patient with cervical disc herniation was higher than that of the other vertebrae.Additionally,the joint motion range of each cervical spine segment in normal adolescent was greater than that in adolescent patient with cervical disc herniation.(2)In the cervical spine model of normal adolescent,the maximum stress values in the annulus fibrosus and nucleus pulposus were found on the left side during C2-3 flexion conditions(0.43 MPa and 0.17 MPa,respectively).In the cervical spine model of adolescent patient with cervical disc herniation,the maximum stress values were found on the left side during C7-T1 flexion conditions(0.54 MPa and 0.18 MPa,respectively).(3)In the cervical spine model of normal adolescent,the maximum stress value on the endplate was found on the left side of the upper endplate of C3 during flexion conditions(1.46 MPa).In the model of adolescent patient with cervical disc herniation,the maximum stress value on the endplate was found on the left side of the lower endplate of C7 during flexion conditions(1.32 MPa).(4)In the cervical spine model of normal adolescent,the maximum stress value in the small joint cartilage was found in the C2-3 left rotation conditions(0.98 MPa).In adolescent patient with cervical disc herniation,the stress in the small joint cartilage significantly increased under different conditions,especially in C1-2,with the maximum stress found during left flexion(3.50 MPa).(5)It is concluded that compared to normal adolescent,adolescent patient with cervical disc herniation exhibits altered cervical curvature and a decrease in overall joint motion range in the cervical spine.In adolescent with cervical disc herniation,there is a significant increase in stress on the annulus fibrosus,nucleus pulposus,and endplates in the C7-T1 segment.The stress on the left articular cartilage of the C1-2 is notable.Abnormal cervical curvature may be the primary factor causing these stress changes.

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

BACKGROUND: Valvular heart disease (VHD) has become increasingly common with the aging in China. This study aimed to evaluate regional differences in the clinical features, management strategies, and outcomes of patients with VHD across different regions in China. METHODS: Data were collected from the China-VHD Study. From April 2018 to June 2018, 12,347 patients who presented with moderate or severe native VHD with a median of 2 years of follow-up from 46 centers at certified tertiary hospitals across 31 provinces, autonomous regions, and municipalities in Chinese mainland were included in this study. According to the locations of the research centers, patients were divided into five regional groups: eastern, southern, western, northern, and central China. The clinical features of VHD patients were compared among the five geographical regions. The primary outcome was all-cause mortality or rehospitalization for heart failure. Kaplan-Meier survival analysis was used to compare the cumulative incidence rate. RESULTS: Among the enrolled patients (mean age, 61.96 years; 6877 [55.70%] male), multiple VHD was the most frequent type (4042, 32.74%), which was mainly found in eastern China, followed by isolated mitral regurgitation (3044, 24.65%), which was mainly found in northern China. The etiology of VHD varied significantly across different regions of China. The overall rate of valve interventions was 32.67% (4008/12,268), with the highest rate in southern China at 48.46% (205/423). In terms of procedure, the proportion of transcatheter valve intervention was relatively low compared to that of surgical treatment. Patients with VHD in western China had the highest incidence of all-cause mortality or rehospitalization for heart failure. Valve intervention significantly improved the outcome of patients with VHD in all five regions (all P  <0.05). CONCLUSIONS: This study revealed that patients with VHD in China are characterized by significant geographic disparities in clinical features, treatment, and clinical outcomes. Targeted efforts are needed to improve the management and prognosis of patients with VHD in China according to differences in geographical characteristics. REGISTRATION ClinicalTrials.gov , NCT03484806.
Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Heart Valve Diseases/therapy* ; Kaplan-Meier Estimate ; Tertiary Care Centers ; Treatment Outcome