OBJECTIVE To optimize the water extraction technology for Kaixin granules. METHODS UPLC-MS/MS method was established for the simultaneous determination of ginsenoside Rg1， ginsenoside Re， ginsenoside Rb1， tenuifolin， polygalaxanthone Ⅲ and 3， 6′-disinapoyl-sucrose. An orthogonal test was designed with extraction times， extraction duration， and the volume of added water as factors. Using the contents of the aforementioned six indicator components and the extract yield as evaluation indexes， analytic hierarchy process-entropy weight method was employed to determine the combined weights of each indicator. Subsequently， process optimization and validation were conducted by integrating grey relational analysis （GRA） and back propagation （BP） neural network. RESULTS The water extraction technology optimized by the orthogonal test and GRA was 10- fold water for the first decoction and 8-fold water for the subsequent two， extracting 3 times，extracting for 1 h each time； the average comprehensive score of the validation experiment was 91.10 （RSD＝0.31%， n＝3）. The water extraction technology optimized by BP neural network was extracting 3 times with 10-fold water added each time， extracting for 1.5 h each time； the average comprehensive score of the validation experiment was 95.89 （RSD＝0.73%， n＝3）. Considering practical production requirements， the optimal water extraction technology was extraction performed three times， with 10-fold water for the first decoction and 8-fold water for the subsequent two extractions， with an extraction time of 1 h each. CONCLUSIONS The optimized water extraction technology for Kaixin granules is stable and feasible.

Osteoarthritis （OA） is a common chronic， highly prevalent， painful， and disabling degenerative joint disease. It has imposed a heavy burden on social healthcare and patients' psychology and economy due to its clinical symptoms such as impaired joint mobility and severe joint pain and the immature therapies. Studies have shown that OA is closely associated with articular cartilage dysfunction， synthesis and degradation disorders of chondrocyte extracellular matrix （ECM）， and joint inflammation. Moderate autophagy can restore the function of damaged chondrocytes， regulate chondrocyte apoptosis， and promote the synthesis and metabolism of ECM to alleviate the inflammation of joints and delay the onset and progression of OA. According to the clinical symptoms， OA can be classified into the category of impediment in traditional Chinese medicine. With the theories of holistic conception， treatment based on syndrome differentiation， and individualised diagnosis and treatment， traditional Chinese medicine has demonstrated definite effects in the treatment of OA in thousands of years of practice. Moreover， traditional Chinese medicine causes mild adverse reactions， and the patients have high tolerance and acceptance. This paper briefly explains the roles of autophagy and the related regulatory proteins， such as Unc-51-like autophagy-activated kinase 1 （ULK1）， Beclin-1， and microtubule-associated protein light chain 3 （LC3）， and details the latest research achievements in the prevention and control of OA by traditional Chinese medicines and its related markers via the regulation of autophagy， so as to provide a idea for the in-depth research in this field and the clinical application of traditional Chinese medicine in preventing and treating OA.

The pathogenesis theory of"spleen deficiency and stasis toxin"in gastric cancer holds that spleen is the source of generation and transformation of qi and blood,that spleen deficiency is the internal basis of disease and throughout the disease.Stasis toxin is based on spleen deficiency,which is the fundamental pathogenesis of gastric cancer.In the pathological process of gastric cancer,a variety of metabolic substances in tumor cells and tumor microenvironment,mainly glucose metabolic reprogramming,undergo metabolic changes to reconstruct the phenotype and function of tumor-related macrophages,which is consistent with the pathogenesis theory of"spleen deficiency and stasis toxin".Therefore,this article focused on the reprogramming of glucose metabolism in tumor microenvironment to drive the phenotypic remodeling of tumor-related macrophages,explored the scientific connotation of the pathogenesis theory of"spleen deficiency and stasis toxin"of gastric cancer,and provided references for the theoretical and clinical research on the treatment of gastric cancer by TCM.

ObjectiveTo investigate the effect of Tongxinluo capsules on the use of anti-ischemic drugs in patients with chronic coronary syndrome （CCS） of Qi deficiency and blood stasis. MethodA multicenter，prospective cohort study was conducted，with Tongxinluo capsules intervention as the exposure factor. Patients were divided into an exposed group （combination of traditional Chinese and western medicine） and a non-exposed group （western medicine alone），and followed up for one year. The use of anti-ischemic drugs was observed on the day of enrollment and at 3，6，12 months. ResultA total of 186 patients were enrolled，with 128 in the exposed group and 58 in the non-exposed group. There were no statistically significant differences in baseline characteristics between the two groups. At the 3-month follow-up，the types of first-line anti-ischemic drugs used in the exposed group were significantly fewer than those in the non-exposed group （P<0.01），and this difference remained statistically significant at 6 months （P<0.05） but was no longer significant at 12 months. At the 3- and 6-month follow-ups，there were no significant differences between the two groups in the types of second-line anti-ischemic drugs used. However，at the 12-month follow-up，the types of second-line anti-ischemic drugs used in the exposed group were significantly fewer than those in the non-exposed group （P<0.01）. At the 3-month follow-up，both groups showed a reduction in the types of first-line anti-ischemic drugs used compared to baseline （P<0.05），with a more pronounced reduction in the exposed group （P<0.05）. At the 6-month follow-up，the exposed group showed a significant reduction in the types of second-line anti-ischemic drugs used compared to baseline （P<0.05），while no significant changes were observed in the non-exposed group. At the 12-month follow-up，the difference in the types of second-line anti-ischemic drugs between the exposed and non-exposed groups was statistically significant （P<0.05），while there was no significant difference in the types of first-line anti-ischemic drugs. ConclusionTongxinluo capsules can effectively reduce the use of anti-ischemic drugs in patients with CCS of Qi deficiency and blood stasis.

OBJECTIVE To investigate the correlation between gene polymorphisms and adverse drug reaction （ADR） and demands of opioids， aiming to guide personalized opioid analgesic therapy. METHODS The existing evidence-based medical data were adopted to identify gene loci related to the efficacy and ADR of opioid analgesics and select highly relevant single nucleotide polymorphism （SNP） for a clinical case-control study. The study cohort was divided into two evaluation groups： ADR assessment and drug demand assessment. The ADR assessment group included 254 cancer pain patients and was subdivided into the trial subgroup （with ADR） and the control subgroup （without ADR） based on the presence or absence of ADR following opioid usage； the two subgroups included 126 and 128 patients， respectively. The drug demand assessment group included a total of 120 cancer pain patients， who were divided into trial subgroup （equivalent to a daily dose of oral morphine ≥100 mg） and control subgroup （equivalent to a daily dose of oral morphine ＜100 mg） based on the different daily doses of opioid analgesics， with 60 patients in each subgroup. Polymorphism detection of SNP loci in these patients was performed using fluorescence in situ hybridization. SPSS 21.0 software and SNPStats genetic models were employed to compare genetic testing results between subgroups and conduct correlation analyses， aiming to evaluate the association of the selected SNP loci with opioid ADR and drug demand inclinical real-world cases. RESULTS The strongly correlated SNP loci identified were CYP2D6*10（rs1065852，C＞T）， CYP3A5*3（rs776746，A＞G），ABCB1（rs1045642，C＞T）and OPRM1（rs1799971，A＞G）. Genetic testing results indicated that the allele frequency distributions of these SNP loci conformed to Hardy-Weinberg equilibrium. Correlation analysis revealed that in the ADR assessment group， compared with control subgroup， the proportion of patients in trial subgroup with the AA genotype of OPRM1 （rs1799971， A＞G） was significantly higher （P＜0.05）； in the drug demand assessment group， compared with control subgroup， the proportion of patients in trial subgroup with the CC+CT genotype of ABCB1 （rs1045642， C＞T） was significantly higher （P＜0.05）. CONCLUSIONS The AA genotype of OPRM1 （rs1799971， A＞G） is associated with the occurrence of ADR following oxycodone use. Patients with the CC+ CT genotype of ABCB1（ rs1045642， C＞T） require higher doses of opioid analgesics.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

【Objective】 To investigate the preoperative epidemiological factors affecting the surgical outcomes of transurethral resection of the prostate (TURP) in patients with benign prostatic hyperplasia (BPH) and to evaluate the clinical predictive value. 【Methods】 Patients undergoing TURP at our hospital during Dec.2018 and Sep.2021 whose pathological examination suggestive of BPH were involved. Before operation, the clinical data, International Prostate Symptom Score (IPSS), quality of life (QoL) score, overactive bladder (OAB) score, prostate-specific antigen (PSA), and urological ultrasound results were collected. After operation, all patients were followed up with telephone call or face-to-face interview, and the IPSS, QoL score and OAB score were examined. Patients were divided into effective and ineffective groups according to the efficacy rubrics. The epidemiological factors affecting the efficacy of TURP were identified with univariate analysis, the independent influencing factors were screened with binary logistic regression, and the diagnostic value of each independent influencing factor was evaluated using receiver operating characteristic (ROC) curve. 【Results】 OAB score (OR=0.749, 95%CI: 0.627-0.895, P=0.001), IPSS-V/S (OR=4.919, 95%CI: 1.617-14.963, P=0.005), history of urinary retention (OR=7.513, 95%CI: 2.289-24.656, P=0.001), and history of urinary incontinence (OR=2.656, 95%CI: 1.015-6.950, P=0.047) were independent influencing factors for poor postoperative outcomes. ROC curve revealed that the area under the ROC curve (AUC) showed that AUC of OAB score, IPSS-V/S, history of urinary retention, and history of urinary incontinence were 0.784 (95%CI: 0.718-0.841), 0.686 (95%CI: 0.614-0.751), 0.713 (95%CI: 0.643-0.777), and 0.723 (95%CI: 0.654-0.786), respectively. ROC curve of the regression model showed that the AUC was 0.888 (95%CI: 0.834-0.930), and the sensitivity and specificity were 93.53% and 67.35%, respectively. 【Conclusion】 Preoperative OAB score, IPSS-V/S, history of urinary retention, and history of urinary incontinence were independent epidemiological factors of poor outcomes after TURP in BPH patients. The diagnostic efficacy ranked from the highest to the lowest as regression model >OAB score>history of urinary incontinence >history of urinary retention>IPSS-V/S.

Objective To explore the role of G protein pathway suppressor 2(GPS2)in regulating proliferation,migration and invasion in hepatocellular carcinoma cell line MHCC-97H.Methods The expression of GPS2 in hepatocellular carcinoma(HCC)cells were detected using quantitative PCR or Western blot;GPS2 was either over-expressed or knocked down in HCC cells using over-expression vectors or short hairpin RNAs(shRNAs)for GPS2,respectively.Clone formation assay,scratch assay and Transwell assay were used to detect the effects of GPS2 on proliferation,migration and invasion of HCC cells.Results In HCC cells,over-expression of GPS2 was found to inhibit the proliferation,migration and invasion of HCC cells MHCC-97H,while knockdown of GPS2 up-regulated proliferation,migration and invasion of MHCC-97H(P＜0.05).The over-expression of GPS2 in MHCC-97H cells was found to inhibit the expression of cell proliferation,migration and invasion-related factors such as EGFR,MMP1,MMP3 and MMP9,while knockdown of GPS2 upregulated the expression of these factors(P＜0.05).Conclusions GPS2 is a novel HCC regulatory factor that inhibits proliferation,migration and invasion of HCC cells.

Cardiovascular diseases are the leading cause of death in the world today. Atherosclerosis （AS） is a chronic inflammatory disease characterized by thickening or functional degeneration of the arterial wall， and in the later stage of the disease， plaque ruptures to induce thrombosis， which in turn causes ischemia in tissues or organs. It is therefore the pathological basis for all types of cardiovascular diseases. Nuclear transcription factor kappa B （NF-κB）， an important nuclear transcription factor in the inflammatory response， is activated to mediate the transcription of inflammatory factors that can trigger or exacerbate the development of AS. Vascular endothelial cells are activated by inflammatory factors. NF-κB mediates related regulatory genes in endothelial cells to secrete adhesion molecules， chemokines， and coagulation factors， promotes selective aggregation of monocytes， up-regulates the expression of adhesion molecules to make adhesion molecules stick to the endothelium and move toward the intima， promotes the degradation of the extracellular matrix， and forms unstable plaques. In recent years， traditional Chinese medicine （TCM） has achieved certain results in the prevention and treatment of AS， and many Chinese medicines have been proved to be effective in resisting AS and can act on multiple targets in the human body， affecting the occurrence and development of AS in different links. This paper mainly introduced the NF-κB pathway and its relationship with AS， reviewed research progress on 75 components of different types in Chinese medicine monomers such as flavonoids， terpenoids， and alkaloids in AS resistance based on the NF-κB pathway， and found that Chinese medicine monomers mainly regulate cholesterol balance， inhibit the inflammatory response， reduce cell proliferation， inhibit intercellular adhesion， and suppress foam cell formation by regulating the NF-κB pathway to provide a reference for the prevention and treatment of AS.

Pulp loss is accompanied by the functional impairment of defense, sensory, and nutrition supply. The approach based on endogenous stem cells is a potential strategy for pulp regeneration. However, endogenous stem cell sources, exogenous regenerative signals, and neovascularization are major difficulties for pulp regeneration based on endogenous stem cells. Therefore, the purpose of our research is to seek an effective cytokines delivery strategy and bioactive materials to reestablish an ideal regenerative microenvironment for pulp regeneration. In in vitro study, we investigated the effects of Wnt3a, transforming growth factor-beta 1, and bone morphogenetic protein 7 (BMP7) on human dental pulp stem cells (h-DPSCs) and human umbilical vein endothelial cells. 2D and 3D culture systems based on collagen gel, matrigel, and gelatin methacryloyl were fabricated to evaluate the morphology and viability of h-DPSCs. In in vivo study, an ectopic nude mouse model and an in situ beagle dog model were established to investigate the possibility of pulp regeneration by implanting collagen gel loading BMP7. We concluded that BMP7 promoted the migration and odontogenic differentiation of h-DPSCs and vessel formation. Collagen gel maintained the cell adhesion, cell spreading, and cell viability of h-DPSCs in 2D or 3D culture. The transplantation of collagen gel loading BMP7 induced vascularized pulp-like tissue regeneration in vivo. The injectable approach based on collagen gel loading BMP7 might exert promising therapeutic application in endogenous pulp regeneration.
Animals ; Bone Morphogenetic Protein 7/pharmacology* ; Cell Differentiation ; Cells, Cultured ; Collagen/pharmacology* ; Dental Pulp ; Dogs ; Endothelial Cells ; Gelatin ; Humans ; Methacrylates ; Mice ; Regeneration ; Stem Cells