BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

Cation exchange chromatography, as a commonly used separation and purification technique in biopharmaceutical manufacturing, is often employed for downstream processes to separate target monoclonal antibodies from their charge variants. For samples with complex and poorly resolved charge variant profiles, the collection solely based on ultraviolet detection does not provide specific compositional information for individual charge variants, making it challenging to determine the range of pooled fractions directly. Subsequent laborious fractionation analysis is then required to guide collection according to production requirements. A mechanistic model for the cation exchange chromatography process of the target monoclonal antibody's critical components was established, and it was employed to assist in product collection. The model accurately predicted the elution peak shapes of the modeled variants, with a root mean square error between predicted and actual values below 0.009. In comparison to the online ultraviolet-based collection method, the model-assisted collection method not only visualized the chromatographic process but also increased the relative productivity by fourfold while ensuring compliance rate.

Osteoporosis leads to an imbalance in bone remodelling, where bone resorption is greater than bone formation and osteoclast degradation increases, resulting in severe bone loss. Autophagy is a lysosomal degradation pathway that regulates the proliferation, differentiation, and apoptosis of various bone cells (including osteoblasts, osteoclasts, and osteoclasts), and is deeply involved in the bone remodelling process. In recent years, the role of autophagy in the progression of osteoporosis and related bone metabolic diseases has received more and more attention, and it has become a research hotspot in this field. Summarising the existing studies, it is found that senile osteoporosis is the result of a combination of factors. On the one hand, it is the imbalance of bone remodelling and the increase of bone resorption/bone formation ratio with ageing, which causes progressive bone loss. On the other hand, aging leads to a general decrease in the level of autophagy, a decrease in the activity of osteoblasts and osteoclasts, and an inhibition of osteogenic differentiation. The lack of oestrogen leads to the immune system being in a low activation state, and the antioxidant capacity is weakened and inflammatory response is increased, inducing autophagy-related proteins to participate in the transmission of inflammatory signals, excessive accumulation of reactive oxygen species (ROS) in the skeleton, and negatively regulating bone formation. In addition, with aging and the occurrence of related diseases, glucocorticoid treatments also mediate autophagy in bone tissue cells, contributing to the decline in bone strength. Exercise, as an effective means of combating osteoporosis, improves bone biomechanical properties and increases bone density. It has been found that exercise induces oxidative stress, energy imbalance, protein defolding and increased intracellular calcium ions in the organism, which in turn activates autophagy. In bone, exercise of different intensities activates messengers such as ROS, PI3K, and AMP. These messengers signal downstream cascades, which in turn induce autophagy to restore dynamic homeostasis in vivo. During exercise, increased production of AMP, PI3K, and ROS activate their downstream effectors, AMPK, Akt, and p38MAPK, respectively, and these molecules in turn lead to activation of the autophagy pathway. Activation of AMPK inhibits mTOR activity and phosphorylates ULK1 at different sites, inducing autophagy. AMPK and p38 up-regulate per-PGC-1α activity and activate transcription factors in the nucleus, resulting in increased autophagy and lysosomal genes. Together, they activate FoxOs, whose transcriptional activity controls cellular processes including autophagy and can act on autophagy key proteins, while FoxOs proteins are expressed in osteoblasts. Exercise also regulates the expression of mTORC1, FoxO1, and PGC-1 through the PI3K/Akt signalling pathway, which ultimately plays a role in the differentiation and proliferation of osteoblasts and regulates bone metabolism. In addition, BMPs signaling pathway and long chain non-coding RNAs also play a role in the proliferation and differentiation of osteoblasts and autophagy process under exercise stimulation. Therefore, exercise may become a new molecular regulatory mechanism to improve osteoporosis through the bone autophagy pathway, but the specific mechanism needs to be further investigated. How exercise affects bone autophagy and thus prevents and treats bone-related diseases will become a future research hotspot in the fields of biology, sports medicine and sports science, and it is believed that future studies will further reveal its mechanism and provide new theoretical basis and ideas.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective To investigate the effect and mechanism of hypericin on osteoporosis(OP)in rats with chronic obstructive pulmonary disease(COPD).Methods COPD combined with OP rat model was established by cigarette combined with bacteria.The rats were randomly divided into control group,model group(COPD combined with OP model was constructed),experimental-L group(50 mg·kg-1 hypericin was given by intragastric administration after constructing COPD combined with OP model),experimental-H group(100 mg·kg-1 hypericin was given intragastric administration after constructing COPD combined with OP model),positive group(subcutaneous injection of 16 U·kg-1 salmon calcitonin after constructing COPD combined with OP model);each group was given 12 rats for 90 days.The lung function of rats was detected by pulmonary function apparatus;bone mineral density(BMD)was detected by micro-computed tomography(CT);serum bone metabolism and inflammatory factors were detected by enzyme-linked immunosorbent assay(ELISA);Western blot assay was used to detect the relevant indicators of the pathway.Results The levels of forced vital capacity(FVC)in control group,model group,experimental-H group and positive group were(10.42±1.40),(4.10±0.60),(6.75±0.37),(4.18±0.33)mL,respectively;BMD levels were(0.31±0.04),(0.12±0.02),(0.28±0.03),(0.29±0.04)g·mm-3,respectively;bone alkaline phosphatase(BALP)levels were(200.04±20.03),(80.80±6.00),(148.16±14.23),(173.97±23.55)U·L1,respectively;interleukin-1β(IL-1β)levels were(122.60±8.70),(695.59±74.84),(422.41±44.86),(527.90±39.36)pg·mL-1,respectively;phosphorylated p38 mitogen-activated protein kinase(p-P38)protein expression levels were 0.99±0.11,0.36±0.05,0.79±0.08,0.36±0.04,respectively.Compared with the control group,the above indexes in the model group had statistical significance(all P＜0.05);the above indexes in experimental-H group were significantly different from those in model group(all P＜0.05).Conclusion Hypericin can inhibit inflammatory response,improve bone metabolism and biomechanics.

Objective:To summarise and analyse the experience in the diagnosis and management of abdominal aortic endograft infection in recent years.Methods:Retrospectively summarised and analysed the general data, clinical presentation, laboratory and imaging findings, causative organisms and treatment choices of 14 patients with abdominal aortic endograft infection treated in Beijing Friendship Hospital, Capital Medical University, from January 2018 to June 2024, and analysed the prognosis of the patients and the risk factors associated with prognosis.Results:Positive bacterial cultures were 10 out of 14 patients. One non-operatively treated patient died of infectious toxic shock. Thirteen surgically treated patients underwent axillary-bifemoral artery bypass, removal of the infected stent, and closure of the aortic stump. Four of the 13 cases had combined aortoenteric fistula, 3 cases underwent one-stage enterocutaneous fistula repair, 1 case only fistula drainage, 3 cases of gastrojejunal anastomosis, all of them underwent gastric or jejunal nutrient tube implantation. Two of the 13 patients had combined the infection foci spread to the renal artery openings. To save the kidney, intraoperative left kidney autologous renal transplantation was performed in 1 case, and autologous saphenous vein reconstruction from celiac trunk artery-left renal artery and superior mesenteric artery-right renal artery was performed in the other case. All 14 patients were retrospectively summarised and followed up in August 2024, with 5 deaths in the early postoperative period (< 3 months), 3 deaths in the mid- to long-term period (≥3 months), and 5 survivors, with a median follow-up time of 2 years (1-5 years) for surviving patients. Among the 13 operated patients, 4 cases were combined with aortoenteric fistula, and 3 cases died in the early postoperative period; 4 cases of abdominal aortic infection foci involving renal artery openings, 2 cases of early postoperative death; 4 cases with pleural effusion, 4 cases died in the early postoperative period; 2 cases of combined creatinine elevation, 2 cases of early postoperative death; 2 cases of postoperative infection of artificial blood vessels.Conclusions:Abdominal aortic endograft infection are aggressive. The risk of early death is increased in patients who are elderly, in poor general condition, with aortoenteric fistula or with pre-existing cardiac, pulmonary, hepatic and renal insufficiency, but surgery based on adequate anti-infective therapy remains an effective means of saving the patient′s life.

Objective To explore the clinical efficacy and safety of Beimu Zhizhu Prescription(derived from the modification of Zhizhu Pills)in the treatment of GERC by retrospectively analyzing the clinical data of 297 patients with gastroesophageal reflux cough(GERC).Methods A retrospective cohort study was conducted in a total of 297 patients with GERC of rebellious stomach qi type who were admitted to the Outpatient Department of Wangjing Hospital of China Academy of Chinese Medical Sciences from July 2021 to July 2023.The patients were divided into an exposure group(136 cases)and a non-exposure group(161 cases)according to the medication of Beimu Zhizhu Prescription or not.The exposure group was treated with Beimu Zhizhu Decoction,and the non-exposure group was treated with proton pump inhibitor of Esomeprazole Magnesium Enteric-coated Tablets.A total of 119 pairs of cases were obtained after propensity score matching(PSM)at the ratio of 1 to 1.The changes of salivary pepsin level before and after treatment in the two groups were observed.After two weeks and eight weeks of treatment,the cough response rate and the remission rates for reflux-related symptoms of acid reflux,heartburn,belching and gastric distension were compared between the two groups,and the incidence of adverse reactions was recorded.Results(1)After two weeks of treatment,the comparison of symptom remission rate after PSM showed that the cough response rate and the remission rates for reflux-related symptoms of acid reflux,heartburn,belching and gastric distension in the exposure group were 84.87％(101/119),80.77％(84/104),82.61％(76/92),82.5％(66/80),84.42％(65/77),respectively,and those in the non-exposure group were 73.95％(88/119),72.90％(78/107),70.41％(69/98),65.38％(51/78),64.38％(47/73),respectively.The intergroup comparison showed that the remission rates for all of the symptoms except for acid reflux in the exposure group was significantly superior to that in the non-exposure group(P＜0.05 or P＜0.01).After eight weeks of treatment,the cough response rate and the remission rates for reflux-related symptoms of acid reflux,heartburn,belching,and gastric distension in the exposure group were 94.74％(36/38),91.67％(33/36),91.43％(32/35),93.75％(30/32),94.12％(32/34),respectively,and those in the non-exposure group were 77.78％(35/45),74.42％(32/43),71.43％(30/42),68.42％(26/38),66.67％(24/36),respectively.The intergroup comparison showed that the remission rate of all of the symptoms in the exposure group was significantly superior to that in the non-exposure group(P＜0.05 or P＜0.01).(2)After two weeks of treatment,the comparison of salivary pepsin level after PSM showed that the salivary pepsin level of the exposure group was significantly lower than that before treatment(P＜0.01),while that of the non-exposure group was not significantly decreased(P＞0.05).The decrease of salivary pepsin level in the exposure group was significantly superior to that in the non-exposure group.Statistically significant differences were presented in the post-treatment salivary pepsin level after two weeks of treatment and in the pre-and post-treatment difference of salivary pepsin level between the two groups(P＜0.05 or P＜0.01).(3)There were four cases(2.48％)of adverse reactions in the non-exposure group,while no related adverse reactions occurred in the exposure group.There was no significant difference in the incidence of adverse reactions between the two groups(x2=1.180,P=0.178).Conclusion Beimu Zhizhu Decoction can effectively relieve cough and reflux-related symptoms of acid reflux,heartburn,belching,and gastric distension in patients with GERC of rebellious stomach qi type,reduce the level of salivary pepsin,and has high safety.

Based on the long bud stage phenotype of a new Lonicera japonica Flos variety "Huajin 6", using "Huajin 6" and "Da Mao Hua" as materials, probing the mechanism of its phenotype formation. Detection of endogenous Jasmonic acid hormones (JAs) content; the genes related to jasmonic acid (JA) synthesis were identified by transcriptome analysis of Lonicera japonica; flower buds and flowers of "Huajin 6" and "Da Mao Hua" were collected at different periods, and the qRT-PCR (quantitative real-time PCR) technique was used to analyze the trend of the expression of synthesis-related enzyme genes in Lonicera japonica Flos during the bud stage. The study found that the content of JAs in "Huajin 6" Lonicera japonica Flos was significantly lower than that in "Da Mao Hua"; applying exogenous methyl-jasmonate (MeJA) to "Huajin 6" can restore its flowering phenotype, making it close to wild type Lonicera japonica Flos; there are significant differences in the expression of two allene oxide synthase genes (AOS), three lipoxygenase genes (LOX), and two allene oxide cyclase genes (AOC) in the flowers and buds of "Huajin 6" and "Da Mao Hua" at different periods. It is hypothesized that the low expression of JA synthesis-related enzyme genes in " Huajin 6" leads to the blockage of JA synthesis, which causes the formation of the long bud phenotype. This study laid a certain foundation for the genetic breeding of Lonicera japonica, provided a new idea for the improvement of Lonicera japonica varieties, and provided a reference for the study of JAs in plant flower organs.

Objective To explore the effect of CircCSNK1G1 on the proliferation,apoptosis and migration of gastric cancer(GC)cells by regulating the miR-381-3p/S kinase-related protein 2(Skp2)axis.Methods HGC-27 cells were divided into non transfected group,si-NC group,si-CircCSNK1G1 group,si-CircCSNK1 G1+anti-miR-NC group,and si-CircCSNK1G1+anti-miR-381-3p group.The expressions of CircCSNK1G1,miR-381-3p and Skp2 mRNA in GC tumor tissues and GC cell lines were detected by qRT-PCR respectively;cell proliferation was detected by MTT assay;the number of cell clones was detected by clonogenic assay;apoptosis was detected by flow cytometry;cell migration and invasion ability were determined by transwell;the expression of E-cadherin and Vimentin was detected by Western Blot;and the targeting relationship among CircCSNK1G1,miR-381-3p and Skp2 was verified by double luciferase experiment.Results Compared with GES-1 in normal tissues adjacent to cancer and normal human gastric mucosal epithelial cells,the expression of CircCSNK1 G1 and Skp2 mRNA in GC tumor tissues and GC cell lines is high,and the expression of miR-381-3p is low(P＜0.05),and the expression level of miR-381-3p in HGC-27 cells is the lowest,and the expression level of CircCSNK1G1 and Skp2 mRNA is the highest,therefore,HGC-27 cells were selected and CircCSNK1G1 was knocked down for the experiment.Compared with untransfected group and si-CircCSNK1G1-NC group,transfection of si-CircCSNK1G1 could reduce the expression of CircCSNK1G1,Skp2 mRNA,cell proliferation activity,cell migration number,and the expression of Vimentin protein in HGC-27 cells(P＜0.05),the expression of miR-381-3p,apoptosis rate,and the expression of E-cadherin protein were increased(P＜0.05).The double luciferase experiment verified that CircCSNK1G1 and Skp2 had a targeting relationship with miR-381-3p,moreover,CircCSNK1G1 could be used as sponge RNA of miR-381-3p to further regulate the expression and activity of Skp2.Conclusion Knockdown of CircCSNK1G1 can target up-regulate the expression of miR-381-3p,and inhibit the expression of Skp2,thus promoting the apoptosis of GC cells,and inhibiting their proliferation and migration.