Ovarian cancer （OC） is a common gynecological malignant tumor in clinical practice. In the early stage，it is often asymptomatic，while in the late stage，it mainly presents with non-specific symptoms such as abdominal distension，poor appetite，and dull abdominal pain. Some patients may also have cachexia such as weight loss and anemia. Early diagnosis is difficult，and the mortality rate ranks first among gynecological malignant tumors，making OC a major challenge in clinical treatment. The classic Chinese medicine formula Guizhi Fulingwan comes from the Jingui Yaolue and has the effects of promoting blood circulation，removing blood stasis，and reducing abdominal lumps. In recent years，it has been widely used to treat OC with good results. This article summarized the clinical application of Guizhi Fulingwan in the treatment of OC from two aspects：The analysis of its basic prescriptions and clinical research. In terms of basic prescriptions，the formula has the ability to promote blood circulation，remove blood stasis，and reduce abdominal lumps. It can exert therapeutic effects considering both water and blood aspects and reduce abdominal lumps， with characteristics of simultaneous Yang warming and heat clearing and parallel supplementation and elimination. Through the methods of "circulation" and "supplementation"， it strengthens the body，dispels evil，and eliminates underlying symptoms. In clinical studies，Guizhi Fulingwan can be applied to various stages of patients with OC，which not only promotes the recovery of the body after OC surgery but also can be combined with chemotherapy and immunotherapy to synergistically treat advanced OC and enhance treatment efficacy. In addition，the formula can also alleviate various adverse reactions caused by chemotherapy，with high safety，improve patients' quality of life，prolong survival，and optimize tumor control effects. Based on the above analysis，this article elaborated on the current clinical research status of Guizhi Fulingwan combined with Western medicine in the treatment of OC and proposed suggestions and improvements to address the shortcomings in current clinical research，so as to provide reference for the clinical application of this formula in the treatment of OC and the construction of a combined traditional Chinese and Western medicine treatment model.

Ovarian cancer （OC） is a common gynecological malignant tumor in clinical practice. In the early stage，it is often asymptomatic，while in the late stage，it mainly presents with non-specific symptoms such as abdominal distension，poor appetite，and dull abdominal pain. Some patients may also have cachexia such as weight loss and anemia. Early diagnosis is difficult，and the mortality rate ranks first among gynecological malignant tumors，making OC a major challenge in clinical treatment. The classic Chinese medicine formula Guizhi Fulingwan comes from the Jingui Yaolue and has the effects of promoting blood circulation，removing blood stasis，and reducing abdominal lumps. In recent years，it has been widely used to treat OC with good results. This article summarized the clinical application of Guizhi Fulingwan in the treatment of OC from two aspects：The analysis of its basic prescriptions and clinical research. In terms of basic prescriptions，the formula has the ability to promote blood circulation，remove blood stasis，and reduce abdominal lumps. It can exert therapeutic effects considering both water and blood aspects and reduce abdominal lumps， with characteristics of simultaneous Yang warming and heat clearing and parallel supplementation and elimination. Through the methods of "circulation" and "supplementation"， it strengthens the body，dispels evil，and eliminates underlying symptoms. In clinical studies，Guizhi Fulingwan can be applied to various stages of patients with OC，which not only promotes the recovery of the body after OC surgery but also can be combined with chemotherapy and immunotherapy to synergistically treat advanced OC and enhance treatment efficacy. In addition，the formula can also alleviate various adverse reactions caused by chemotherapy，with high safety，improve patients' quality of life，prolong survival，and optimize tumor control effects. Based on the above analysis，this article elaborated on the current clinical research status of Guizhi Fulingwan combined with Western medicine in the treatment of OC and proposed suggestions and improvements to address the shortcomings in current clinical research，so as to provide reference for the clinical application of this formula in the treatment of OC and the construction of a combined traditional Chinese and Western medicine treatment model.

BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Zishen Huoxue decoction (ZSHX) enhances cardiomyocyte viability following hypoxic stress; however, its upstream therapeutic targets remain unclear. Network pharmacology and RNA sequencing analyses revealed that ZSHX target genes were closely associated with mitophagy and apoptosis in the mitochondrial pathway. In vitro, ZSHX inhibited pathological mitochondrial fission following hypoxic stress, regulated FUN14 domain-containing protein 1 (FUNDC1)-related mitophagy, and increased the levels of mitophagy lysosomes and microtubule-associated protein 1 light chain 3 beta II (LC3II)/translocase of outer mitochondrial membrane 20 (TOM20) expression while inhibiting the over-activated mitochondrial unfolded protein response. Additionally, ZSHX regulated the stability of beta-tubulin through Sirtuin 5 (SIRT5) and could modulate FUNDC1-related synergistic mechanisms of mitophagy and unfolded protein response in the mitochondria (UPR^mt) via the SIRT5 and -β-tubulin axis. This targeting pathway may be crucial for cardiomyocytes to resist hypoxia. Collectively, these findings suggest that ZSHX can protect against cardiomyocyte injury via the SIRT5-β-tubulin axis, which may be associated with the synergistic protective mechanism of SIRT5-β-tubulin axis-related mitophagy and UPR^mt on cardiomyocytes.
Mitophagy/drug effects* ; Tubulin/genetics* ; Animals ; Myocytes, Cardiac/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Sirtuins/genetics* ; Unfolded Protein Response/drug effects* ; Myocardial Ischemia/genetics* ; Rats ; Humans ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Male

Objective To investigate the expression of prolyl 4-hydroxylase β-polypeptide(P4HB)in glioblastoma multiforme(GBM)and its impact on clinical prognosis,as well as on the proliferation and migration of U87 cells.Methods(1)According to the Cancer Genome Atlas(TCGA)database,GTEx database and GEPIA2 database,the difference expression of P4HB in GBM and normal brain tissues were analyzed by R software.(2)A total of 52 patients with GBM who underwent surgical treatment from February 2017 to December 2019 were collected from Department of Neurosurgery,the Second People's Hospital of Guiyang.The normal brain tissues of 10 patients were selected as controls.Immunohistochemical method was used to detect the expression level of P4HB in tumor tissues and normal tissues.The Kaplan-Meier method with the log-rank test was employed for survival analysis.Receiver operating characteristic(ROC)curve was used to analyze the predictive valuable of P4HB expression in survival rate of GBM.Univariate and multivariate Cox regression analysis were used to identify the expression of P4HB and related clinicopathological factors affecting the survival and prognosis of the patients.(3)Human GBM U87 cells were randomly assigned into three groups:control group,NC-siRNA group and P4HB-siRNA group.P4HB expression was interfered with by the transfection of siRNA in P4HB-siRNA group.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the content of P4HB mRNA in U87 cells.Cell counting kit-8(CCK-8)and immunofluorescence assay were used to analyze the effects of P4HB on the proliferation of U87 cells.Scratch test was used to analyze the effects of P4HB on cell migration.Results The expression of P4HB was significantly upregulated in GBM tissues compared with normal brain tissues(P<0.05).The γδ T cells(r=-0.227)and follicular helper T cells(r=-0.226)were negatively correlated with the expression of P4HB,while natural killer cell(r=0.417),macrophages(r=0.374),neutrophils(r=0.344),and immature dendritic cells(r=0.263)were positively correlated with the expression of P4HB.Kaplan-Meier survival analysis showed that the progression-free survival and disease-specific survival of GBM patients with high P4HB expression were significantly lower than those with low expression(P<0.05).ROC curve showed that the area under the curve(AUC)of P4HB in predicting overall survival rate of GBM patients was 0.982,and 1-year,3-year,and 5-year survival was 0.655,0.724,0.861,respectively.The immunohistochemistry results suggested that P4HB protein was significantly highly expressed in GBM tumors.Survival analysis indicated that high expression of P4HB was associated with bad prognosis in GBM patients(P<0.05).Multivariate Cox regression analysis indicated that high expression of P4HB and TERT promoter mutations were the independent prognostic risk factors for GBM(P<0.05).Compared with control group and NC-siRNA group,the expression levels of P4HB were decreased significantly after transfected with siRNA in U87 cells of P4HB-siRNA group(P<0.01),and the proliferation ability and the wound healing rate were decreased significantly in P4HB-siRNA group(P<0.001).Conclusions P4HB is significantly highly expressed in GBM,which indicates that the prognosis of patients is poor.Knockout of P4HB could inhibit cellular proliferation and migration of GBM U87 cells.P4HB may be used as the relevant predictive marker and potential therapeutic target in GBM.

Objective To investigate the nutritional status of children with Crohn's Disease (CD) at diagnosis and its association with clinical characteristics. Methods A retrospective analysis was performed for the clinical data and nutritional status of 118 children with CD who were admitted to Beijing Children's Hospital,Capital Medical University,from January 2016 to January 2024. A multivariate logistic regression analysis was used to investigate the risk factors for malnutrition. Results A total of 118 children with CD were included,among whom there were 68 boys (57.6％) and 50 girls (42.4％),with a mean age of (11±4) years. Clinical symptoms mainly included recurrent abdominal pain (73.7％,87/118),diarrhea (37.3％,44/118),and hematochezia (32.2％,38/118),and 63.6％ (75/118) of the children had weight loss at diagnosis. The incidence rate of malnutrition was 63.6％ (75/118),and the children with moderate or severe malnutrition accounted for 67％ (50/75). There were 50 children (42.4％) with emaciation,8 (6.8％) with growth retardation,and 9 (7.6％) with overweight or obesity. Measurement of nutritional indices showed a reduction in serum albumin in 83 children (70.3％),anemia in 74 children (62.7％),and a reduction in 25 hydroxyvitamin D in 15 children (60％,15/25). The children with malnutrition had significantly higher disease activity,proportion of children with intestinal stenosis,and erythrocyte sedimentation rate and a significant reduction in serum albumin (P<0.05). The multivariate logistic regression analysis showed that intestinal stenosis was an independent risk factor for malnutrition in children with CD (OR=4.416,P<0.05). Conclusions There is a high incidence rate of malnutrition in children with CD at diagnosis,which is associated with disease activity and disease behavior. The nutritional status of children with CD should be closely monitored.

Objective:To analyze the etiology of chronic pancreatitis(CP) and evaluate the impact of different intervention methods on the prognosis.Methods:This is a retrospective analysis conducted on clinical data of pediatric patients with CP admitted to Beijing Children's Hospital between January 2010 and December 2023,including etiology,clinical manifestations,imaging data and treatments.Follow-up assessments included height,weight,complications occurrence,and long-term nutritional status evaluated by using Z scores.Results:A total of 98 patients with CP were included in the study,containing 51 males and 47 females,with an age range of 1.95 to 15.96 years (median 8.49 years).The etiological contained the gene mutation (39.8%,39/98) (involving PRSS1, SPINK1, CFTR),the anatomical abnormality (26/98,26.5%),idiopathic pancreatitis (33.7%,33/98).Predominant clinical manifestations included abdominal pain (79/98,79.6%),nausea/vomit(48/98,49.0%),chest tightness/chest pain (10/98,10.2%),with malnutrition (44/98,44.9%) and the serum amylase increased in some patients.Imaging findings revealed heterogeneous pancreatic echoes,dilated pancreatic ducts and pancreatic stones via abdominal ultrasound,and a full or atrophic pancreas with irregular margins,tortuous or dilated pancreatic ducts through abdominal magnetic resonance imaging.Compared with CP caused by other reasons,hereditdry CP had a higher rate of pancreatic morphological changes(100.0% vs.88.1%, P<0.05).By March 2024,follow-up showed all 98 patients underwent initial medical treatment,followed by surgical intervention in 13 cases,endoscopic retrograde cholangiopancreatography intervention in 51 cases,and no surgical or endoscopic intervention in 34 cases.Six children developed diabetes,six had reduced fecal pancreatic elastase-1 but without fat diarrhea.Long-term follow-up indicated improved nutritional status among children who underwent endoscopic retrograde cholangiopancreatography intervention(Z score,-1.22 vs.0.74, P<0.001). Conclusion:Gene mutations and anatomical abnormalities is the main etiological factors in pediatric patients with CP.Early endoscopic intervention can significantly improve the long-term prognosis of the children.

Objective:To observe the effects of high index of nutritional quality (INQ) enteral nutrition on clinical outcomes in elderly patients with acute heart failure. Methods:70 elderly patients with acute heart failure who had nutritional risk and needed nasal-feeding from the Department of Geriatrics of Hangzhou Ninth People's Hospital and the 903 Hospital of PLA Joint Support Force Hospital were randomly divided into observation group (n=35) and control group (n=35). Patients in the observation group was treated with high INQ enteral nutrition. After 4 weeks of intervention, the difference of energy and protein supply, parenteral nutrition use, nutrition index, cardiac function index and incidence of gastrointestinal adverse reaction were compared between the two groups. Results:After intervention, the energy and protein supply of nasal-feeding in the observation group were significantly higher than those in the control group (P<0.05) , and the amount of parenteral nutrition used in the observation group was significantly lower than that in the control group (P<0.05). The nutritional indexes and cardiac function indexes of the two groups were significantly improved compared with those before intervention, and the nutritional status of the patients in the observation group was improved more significantly (P<0.05). There was no significant difference in the incidence of gastrointestinal adverse reactions between the two groups (P>0.05) . Conclusion:High INQ enteral nutrition can meet the nutritional requirements of elderly patients with heart failure, reduce the use of parenteral nutrition, improve the nutritional status, and promote the recovery of cardiac function.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.