The study explores the traditional Chinese medicine （TCM） diagnostic and treatment approach to coronary microvascular disease （CMVD） from the perspective of "disharmony of blood collaterals and dysfunction of qi transformation". It is proposed that the core pathogenesis of CMVD lies in these two mechanisms. From an integrative medicine perspective， different CMVD types are analyzed based on their specific pathogenesis. Through clinical practice， four targeted treatment methods， i.e. warming， unblocking， tonifying， and activating， are formulated. CMVD caused by atherosclerosis is primarily associated with myocardial ischemia， myocardial infarction， and coronary revascularization， with corresponding pathological mechanisms of latent pathogenic obstruction， toxic accumulation in the collaterals， and deficiency with collateral stasis. The disease progression exhibits characteristics of correlation， staging， and transformation. Accordingly， treatment principles include warming to assist qi transformation， unblocking obstruction and dispelling turbidity， activating to disperse toxic stasis and invigorate collaterals， and tonifying to eliminate stasis and nourish collaterals. For CMVD unrelated to atherosclerosis， attention should be paid to the underlying disease， analyzing the main syndromes of blood and collateral disharmony. An approach combining disease-syndrome differentiation with blood and collateral regulation is emphasized for precise treatment.

Glucose-6-phosphate dehydrogenase (G6PD), the first rate-limiting enzyme of the pentose phosphate pathway (PPP), is aberrantly activated in multiple types of human cancers, governing the progression of tumor cells as well as the efficacy of anticancer therapy. Here, we discovered that cyclin-dependent kinase 5 (CDK5) rewired glucose metabolism from glycolysis to PPP in breast cancer (BC) cells by activating G6PD to keep intracellular redox homeostasis under oxidative stress. Mechanistically, CDK5-phosphorylated G6PD at Thr-91 facilitated the assembly of inactive monomers of G6PD into active dimers. More importantly, CDK5-induced pho-G6PD was explicitly observed specifically in tumor tissues in human BC specimens. Pharmacological inhibition of CDK5 remarkably abrogated G6PD phosphorylation, attenuated tumor growth and metastasis, and synergistically sensitized BC cells to poly-ADP-ribose polymerase (PARP) inhibitor Olaparib, in xenograft mouse models. Collectively, our results establish the crucial role of CDK5-mediated phosphorylation of G6PD in BC growth and metastasis and provide a therapeutic regimen for BC treatment.

The successful operation of the complete digital pathology(CDP) in foreign countries indicates that the full digital pathology process has entered the full implementation stage. Digital pathology in China started late and progressed slowly, so far there has not been a truly meaningful CDP. The pathologist′s understanding of digital pathology is not comprehensive enough, and there are still doubts about the time efficiency and cost effectiveness of digital pathology processes. Therefore,a comprehensive analysis of the process, overall advantages and cost-effectiveness of CDP was made by drawing on international successful experience and hands-on practice experience, in order to promote the construction and development of the CDP in our country.

Based on the clinical thinking of combining diseases and patterns， we combined disease identification， pattern differentiation， and constitution identification， and put forward the theory of identifying and treating critical hypertension， which is "examining the symptoms first， identifying the constitutions as reference， and combining the diseases and patterns". Firstly， the starting point of identifying the disease is to examine the symptoms， and those with precise diagnosis and strong specificity will be diagnosed with the disease， while those with relatively broad diagnosis and fuzzy characteristics will be emphasised on identifying constitutions and differentiating patterns. Focusing on the impact of constitution identification on disease identification and pattern differentiation， constitution identification could be the basis when no symptoms to identify， and based on the theory of "constitution-disease correlation" and "constitution-pattern correlation" to improve the understanding of borderline hypertension from the group and individual level， which helps to identify and predict the development of the diseases and patterns； if the symptoms are complicated and difficult to identify， it is necessary to take syndrome as the outline， use the syndrome to unify the disease， and then refer to the constitution to legislate and prescribe medications. This paper summarizes the traditional Chinese medicine clinical differentiation and treatment strategy of borderline hypertension clear and easy to grasp， with a view to provide a feasible and efficient reference for prevention and treatment of borderline hypertension with traditional Chinese medicine.

Objective:To evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.

Objective To investigate the effects of kuwanon G(KG)on proliferation,apoptosis,migration and invasion of gastric cancer cells and the molecular mechanisms.Methods The effects of KG on proliferation and growth of gastric cancer cells were assessed with CCK-8 assay and cell clone formation assay,by observing tumor formation on the back of nude mice and using immunohistochemical analysis of Ki-67.The effect of KG on cell apoptosis was analyzed using Annexin V-FITC/PI apoptosis detection kit,Western blotting and TUNEL staining.The effects of KG on cell migration and invasion were detected using Transwell migration and invasion assay and Western blotting for matrix metalloproteinase(MMP).The role of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway in KG-mediated regulation of gastric cancer cell proliferation,migration,and invasion was verified by Western blotting and rescue assay.Results KG significantly inhibited proliferation and reduced clone formation ability of gastric cancer cells in a concentration-dependent manner(P<0.05).KG treatment also increased apoptosis,enhanced the expressions of cleaved caspase-3 and Bax,down-regulated Bcl-2,lowered migration and invasion capacities and inhibited the expression of MMP2 and MMP9 in gastric cancer cells(P<0.05).Mechanistic validation showed that KG inhibited the activation of the PI3K/AKT/mTOR pathway,and IGF-1,an activator of the PI3K/AKT/mTOR pathway,reversed the effects of KG on proliferation,migration and invasion of gastric cancer cells(P<0.05).Conclusion KG inhibits proliferation,migration and invasion and promotes apoptosis of gastric cancer cells at least in part by inhibiting the activation of the PI3K/AKT/mTOR pathway.

Objective To evaluate the therapeutic effect of Huangqin Decoction(HQD)on ulcerative colitis(UC)in mice and explore its mechanism.Methods Male Balb/c mice were randomly divided into normal control group,model group,mesalazine group(5-ASA,200 mg/kg),and low-,medium-and high-dose HQD groups(2.275,4.55 and 9.1 g/kg,respectively).With the exception of those in the normal control group,all the mice were exposed to 3%DSS solution in drinking water for 7 days to establish UC models.After treatment with the indicated drugs,the mice were assessed for colon injury and apoptosis using HE,AB-PAS and TUNEL staining,and the expression levels of inflammatory factors were detected with ELISA.Western blotting,immunohistochemistry and qRT-PCR were used to detect the changes in protein expressions associated with the intestinal chemical barrier,mechanical barrier and endoplasmic reticulum stress(ERS).Results HQD treatment significantly reduced DAI score and macro score of UC mice,decreased colonic epithelial cell apoptosis,lowered expressions of IL-6,TNF-α,IL-1β and IL-8,and enhanced the expressions of MUC2 and TFF3.HQD treatment also upregulated the protein expressions of claudin-1,occludin and E-cadherin,reduced the expressions of GRP78,CHOP,caspase-12 and caspase-3,decreased the phosphorylation levels of PERK,eIF2α and IRE1α,and increased the Bcl-2/Bax ratio in the colon tissues of UC mice.Conclusion HQD inhibits colonic epithelial cell apoptosis and improves intestinal barrier function in UC mice possibly by reducing ERS mediated by the PERK and IRE1α signaling pathways.

Objective To investigate the effects of kuwanon G(KG)on proliferation,apoptosis,migration and invasion of gastric cancer cells and the molecular mechanisms.Methods The effects of KG on proliferation and growth of gastric cancer cells were assessed with CCK-8 assay and cell clone formation assay,by observing tumor formation on the back of nude mice and using immunohistochemical analysis of Ki-67.The effect of KG on cell apoptosis was analyzed using Annexin V-FITC/PI apoptosis detection kit,Western blotting and TUNEL staining.The effects of KG on cell migration and invasion were detected using Transwell migration and invasion assay and Western blotting for matrix metalloproteinase(MMP).The role of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway in KG-mediated regulation of gastric cancer cell proliferation,migration,and invasion was verified by Western blotting and rescue assay.Results KG significantly inhibited proliferation and reduced clone formation ability of gastric cancer cells in a concentration-dependent manner(P<0.05).KG treatment also increased apoptosis,enhanced the expressions of cleaved caspase-3 and Bax,down-regulated Bcl-2,lowered migration and invasion capacities and inhibited the expression of MMP2 and MMP9 in gastric cancer cells(P<0.05).Mechanistic validation showed that KG inhibited the activation of the PI3K/AKT/mTOR pathway,and IGF-1,an activator of the PI3K/AKT/mTOR pathway,reversed the effects of KG on proliferation,migration and invasion of gastric cancer cells(P<0.05).Conclusion KG inhibits proliferation,migration and invasion and promotes apoptosis of gastric cancer cells at least in part by inhibiting the activation of the PI3K/AKT/mTOR pathway.

Objective To evaluate the therapeutic effect of Huangqin Decoction(HQD)on ulcerative colitis(UC)in mice and explore its mechanism.Methods Male Balb/c mice were randomly divided into normal control group,model group,mesalazine group(5-ASA,200 mg/kg),and low-,medium-and high-dose HQD groups(2.275,4.55 and 9.1 g/kg,respectively).With the exception of those in the normal control group,all the mice were exposed to 3%DSS solution in drinking water for 7 days to establish UC models.After treatment with the indicated drugs,the mice were assessed for colon injury and apoptosis using HE,AB-PAS and TUNEL staining,and the expression levels of inflammatory factors were detected with ELISA.Western blotting,immunohistochemistry and qRT-PCR were used to detect the changes in protein expressions associated with the intestinal chemical barrier,mechanical barrier and endoplasmic reticulum stress(ERS).Results HQD treatment significantly reduced DAI score and macro score of UC mice,decreased colonic epithelial cell apoptosis,lowered expressions of IL-6,TNF-α,IL-1β and IL-8,and enhanced the expressions of MUC2 and TFF3.HQD treatment also upregulated the protein expressions of claudin-1,occludin and E-cadherin,reduced the expressions of GRP78,CHOP,caspase-12 and caspase-3,decreased the phosphorylation levels of PERK,eIF2α and IRE1α,and increased the Bcl-2/Bax ratio in the colon tissues of UC mice.Conclusion HQD inhibits colonic epithelial cell apoptosis and improves intestinal barrier function in UC mice possibly by reducing ERS mediated by the PERK and IRE1α signaling pathways.

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.