Objective To investigate the expression of YWHAQ protein in gastric adenocarcinoma tissues and its correlation with clinical pathological features and prognosis. Methods A total of 127 patients with gastric cancer who underwent radical surgery were enrolled. Clinical data and postoperative cancer tissue samples were collected from the patients. Immunohistochemistry was used to detect the protein expression of YWHAQ in gastric adenocarcinoma tissues. The relationship between YWHAQ expression and clinical pathological features and prognosis was analyzed. Bioinformatics prediction was performed to identify potential pathways regulated by YWHAQ in gastric adenocarcinoma. A protein-protein interaction network for YWHAQ was constructed using the STRING database. Results YWHAQ gene expression was significantly higher in gastric adenocarcinoma tissues than in normal tissues (P<0.05). The expression level of the YWHAQ protein was significantly correlated with age, tumor invasion depth, lymph node metastasis, and tumor stage (P<0.05). Kaplan-Meier survival analysis showed that patients with high YWHAQ expression had significantly poorer long-term survival than those with low expression (P<0.0001). Cox regression analysis revealed that high YWHAQ expression and distant metastasis were independent risk factors for gastric cancer (HR>1, P<0.05). Enrichment analysis indicated that YWHAQ positively regulated processes such as cell cycle, angiogenesis, and DNA damage repair. Conclusion YWHAQ is highly expressed in gastric adenocarcinoma tissues and may be associated with the occurrence, invasion, and metastasis of gastric adenocarcinoma. High YWHAQ expression and distant metastasis are independent risk factors for the prognosis of gastric adenocarcinoma patients.

To summarise the clinical experience of Professor TONG Xiaolin in treating prediabetes combined with overweight or obesity using the method of relieving depression and reducing turbidity. It is believed that prediabetes belongs to the category of "spleen-heat syndrome" in traditional Chinese medicine， and its core pathogenesis is center fullness with internal heat， while obesity is the initiating factor for exacerbating center fullness and internal heat， therefore， it is of great significance to reduce the risk of diabetes by interrupting the transformation between overweight， obesity and glucose metabolism abnormality. It is proposed that the main pathogenesis of prediabetes combined with overweight or obesity is qi depression and turbidity obstruction in middle jiao， with qi depression as the root and turbidity obstruction as the cause， forming a treatment idea with the method of relieving depression and reducing turbidity as the core. In clinic， Dahuang Huanglian Xiexin Decoction （大黄黄连泻心汤） is used as the basic prescription， with a primary focus on directing the turbid downward， supplemented by regulating qi， which embodies the concept of "promoting movement through descent， then figuring out the root of spleen-heat syndrome. Furthermore， the treatment is flexibly modified based on the patient's deficiency-excess syndrome to ensure individualized therapy.

OBJECTIVE To investigate the activation of xanthine oxidase(XO)from the human liver by vitamin K3 and the mechanism.METHODS Using human liver S9(0.1 g·L-1)as the source,XO was incubated with substrate xanthine of 0,2,4,8,and 16 μmol·L-1 at 37℃ for 90 min.The Michaelis constant(Km)of the reaction of xanthine oxidation was determined using the liquid chromatography diode array method.At the concentration of Km,the three-point method(1,10 and 100 μmol·L-1)was used to detect the activity of vitamin K3 activators.The multi-point method(vitamin K3 1,2,5,10,20,50,100,200 and 400 μmol·L-1)was adopted to determine the half effective concentration(EC50)of activated XO.Kinetic parameters(Km and Vmax)and the fit of double reciprocal curves were determined via vitamin K3 of 1/2EC50,EC50 and 2EC50.The changes in kinetic behavior at different concentrations of vitamin K3 were observed and their types of activation were analyzed.The interactions between XO and activator vitamin K3 were explored via molecular docking.RESULTS The Km of XO-mediated xanthine oxidation reac-tion was 4.71 μmol·L-1.As an activator of this reaction,vitamin K3 activated XO in a concentration-dependent manner(according to the logistic fitting formula y=A2+(A1-A2)/(1+(x/x0)^p),with an EC50 of 32.0 μmol·L-1.The kinetic parameters also changed after the addition of vitamin K3.The Km value decreased(4.71-1.34 μmol·L-1)with the increase of vitamin K3 concentrations,while the Vmax value increased(0.08-1.31 μmol·min-1·g-1),leading to an increase in Vmax/Km(17.0-977.6 mL·min·g-1).In addition,the double reciprocal curve fitting found that the activation type of vitamin K3 on XO was mixed.The molecular docking results showed that vitamin K3 bound to the molybdopterin domain of XO and maintained hydrogen bonding interactions with Arg599 and Ser605.CONCLUSION Vitamin K3 is an activator of XO,which can form hydrogen bonds with Arg599 and Ser605 in the XO domain,regu-late its affinity with the substrate xanthine,activate XO and increase the uric acid level.

Objective The aim of this study was to investigate the prospective association between physical activity (PA),independently or in conjunction with other contributing factors,and osteoporosis (OP) outcomes. Methods The Physical Activity in Osteoporosis Outcomes (PAOPO) study was a community-based cohort investigation. A structured questionnaire was used to gather the participants' sociodemographic characteristics. Bone mineral density (BMD) measurements were performed to assess OP outcomes,and the relationship between BMD and OP was evaluated within this cohort. Results From 2013 to 2014,8,471 participants aged 18 years and older were recruited from Tangshan,China's Jidong community. Based on their PA level,participants were categorized as inactive,moderately active,or very active. Men showed higher physical exercise levels than women across the activity groups. BMD was significantly higher in the very active group than in the moderately active and inactive groups. Individuals aged>50 years are at a higher risk of developing OP and osteopenia. Conclusion The PAOPO study offers promising insights into the relationship between PA and OP outcomes,encouraging the implementation of PA in preventing and managing OP.

Objective:To explore the efficiency of a modified caries risk assessment tool(MCAT)on caries-risk prediction of children in Nanning.Methods:MCAT was designed based on caries-risk assessment tool(CAT)of American Academy of Pediatric Dentistry(AAPD)and the caries related factors of the primary school children in Guangxi,China.A cohort study was conducted in 332 children aged 3-year-old in kindergarten of Jiangnan District,Nanning,Guangxi.The data were integrated through questionnaires and oral exam-ination.The MCAT data were respectively scored by CAT and Cariogram and the caries-risk of the children was evaluated.The develop-ment of increased average caires incidece over a period of 1.5 years was compared,the predictive capacity of the methods was com-pared.Results:The ranks of caires risk assessed by CAT and Cariogram were significant different(Z=-10.34,P＜0.001),and the consistency of the 2 methods was poor(Kappa=0.234,P＜0.001).After 1.5 years,there was significant statistical difference of the caries prevalence rate between the low-high and moderate-high risk groups,and dmft increments between the moderate-high risk groups e-valuated by CAT(P＜0.05).There was significant difference of the caries prevalence rate between each risk groups and dmft increments between the low-high and moderate-high risk groups evaluated by Cariogram(P＜0.05).The AUC of CAT and Cariogram was 0.571 and 0.722 respectively(P＜0.001).In the prediction models of caries risk,the fitting of CAT was poor(P＜0.001),while that of Cariogram was better(P=1.00).Cariogram analysis showed that the chance of developing new caries lesions of the subjects with moderate and high caries risk was 2.86 and 11.65 times more than those with low caries risk.Conclusion:MCAT com-bined with Cariogram can more efficiently predict new caries de-velopment in 3-year-old children.

Objective:To explore the clinical value of a trinity strategy for the treatment of multiple orthopedic trauma.Methods:A retrospective case series study was conducted to analyze the clinical data of 1 267 patients with multiple orthopedic trauma admitted to Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and the First Affiliated Hospital of Navy Medical University from June 2013 to May 2023, including 862 males and 405 females, aged 18-93 years [(55.2±19.8)years]. Associated injuries included hemorrhagic shock in 632 patients, traumatic wet lung in 274, cranial injuries in 135, abdominal and pelvic bleeding in 116, pneumothorax in 89, urinary injury in 13, and vesical rupture in 8. All the patients were treated with the trinity strategy and the treatment process was divided into the phases of first aid, remodeling, and rehabilitation. The first aid phase focused on stabilizing symptoms and saving lives; the remodeling phase centered on restoring the anatomical structure and alignment; the rehabilitation phase aimed for functional recovery through the integration of both Western and traditional Chinese medicine. The all-cause mortality within 30 days after surgery and fracture healing time were calculated; the excellent and good rates of Constant-Murley shoulder score, Mayo elbow score, Gartland-Werley wrist score, Harris hip score, Hospital for Special Surgery (HSS) knee score and the American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot score at the last follow-up and the overall excellent and good rate of all joint function scores were measured. The short form health survey (SF-36) scores were collected preoperatively and at 6 months postoperatively, including 8 aspects such as physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health. The incidence of postoperative complications was recorded.Results:All the patients were followed up for 6-18 months [(10.2±4.2)months]. The mortality rate during the acute phase (within 30 days after surgery) was 2.37% with 12 deaths due to hemorrhagic shock, 10 due to traumatic brain injury, 6 due to multiple organ dysfunction syndrome (MODS), and 2 due to pulmonary infection. The average fracture healing time averaged 3.8-18 months [(11.5±4.2)months], with 89.49% of the patients having bone union within 12 months after surgery, 8.93% having bone union within 18 months after surgery, and 1.58% undergoing reoperation. For the patients with internal fixation failure and nonunion, the average healing time was extended to (10.2±2.2)months and (13.7±3.3)months respectively. At the last follow-up, the excellent and good rates of Constant-Murley shoulder score, Mayo elbow score, Gartland-Werley wrist score, Harris hip score, HSS knee score, and AOFAS ankle-hindfoot score were 83.93%, 90.24%, 94.12%, 85.57%, 88.46%, and 92.31% respectively, with an overall excellent and good rate of 89.11%. At 6 months after surgery, the SF-36 scores of all the patients in the eight dimensions,including the physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health were (74.4±8.6)points, (44.7±14.4)points, (77.4±10.9)points, (68.4±18.2)points, (72.5±16.0)points, (76.8±8.7)points, (49.9±17.6)points, and (72.8±17.9)points, significantly improved compared with those before operation [(63.4±12.7)points, (30.9±17.4)points, (56.4±18.0)points, (55.4±24.7)points, (53.5±21.0)points, (55.8±24.3)points, (36.9±24.0)points, (58.8±21.6)points] ( P<0.01). Complications of different degrees occurred in 214 patients (16.89%), including lung infections in 118 patients (9.31%), lower extremity deep vein thrombosis in 50(3.95%), pressure injuries in 26(2.05%), internal fixation failure in 12(0.95%), and nonunion in 8(0.63%). Conclusions:The trinity strategy provides whole-process management, personalized treatment, and overall rehabilitation for multiple orthopedic trauma. It can decrease mortality, shorten fracture healing time, improve joint function and quality of life, and reduce the incidence of complications.

Objective To optimize the preparation process of Swertia patens,Burk.standard decoction and establish its quality standard by using the quality by design(QbD)concept.Methods Critical Quality Attributes(CQAs)were predicted and analyzed according to the quality marker(Q-marker)theory of traditional Chinese medicine;Failure mode and effects analysis(FMEA)was used to screen critical process parameters(CPPs);The measurement method of key quality attributes was established;The extraction process was optimized by Box Behnken test after the preliminary range was determined according to the single factor test;The entropy method was used for comprehensive scoring;The design space was established and the optimal operation space for process validation was selected;Standard decoction of Swertia patens Burk in fifteen batches with different habitats were prepared with the best technology,and the quality standards for the extraction rate,extract,thin layer chromatography,fingerprint,content,and the content transfer rate were established finally.Results The key quality attributes were swertiamarin content,gentiopicrin content,and paste yield;The key process parameters were soaking time,water amount,and decocting time;The established model had statistical significance;The optimum conditions were as follows:soaking time 90 min,adding water 15 times,decocting time 30 min(second decocting 20 min);The paste yield was 21.13％-30.73％;The extract was 82.00％-88.00％;The spot of swertiamarin was clear in TLC;The similarity between each samples in 15 batches and reference atlas were＞0.85％;The content of swertiamarin was 250.64-385.21 mg·g-1,and the transfer rate was 43.76％-77.73％;The content of gentiopicrin was 0.69-2.70 mg·g-1,and the transfer rate was 56.02％-105.29％.Conclusion Based on the above methods and techniques,the preparation process of Swertia patens Burk.The standard decoction was screened,which provides a reference for the preparation development and quality control of its formula granules.

Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(ROS)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.

Objective This paper explores the role of long-term care insurance(LTCI)in China on the unmet long-term care needs of middle-aged and elderly people and its influencing factors.Methods Based on China health and retirement longitudinal study data for 3 periods from 2013 to 2018.We use difference-in-difference method to explore the impacts of LTCI on unmet long-term care needs of middle-aged and elderly people.Results The implementation of LTCI resulted in an average release of 0.051 long-term care needs(P＜0.1)and an average increase of 0.045 unmet long-term care needs(P＜0.05)among middle-aged and older adults aged 45 years and older in China.Heterogeneity analysis shows that the implementation of LTCI promotes the growth of long-term care needs and unmet needs of residents in urban areas,rural hukou residents,high-income residents and moderately and severely disabled residents.Conclusion Our findings demonstrate the role of LTCI in reducing family caregiving burden and promoting the release of caregiving demand,and provide guidance for the further promotion of LTCI in China.

OBJECTIVE: To explore the diagnostic yield of bronchoscopic rapid on-site evaluation (B-ROSE) in patients with severe invasive bronchopulmonary aspergillosis (IBPA) and provide evidence for starting antifungal treatment before microbiological results were available. METHODS: A prospective cohort study was conducted to select patients with severe pneumonia suspected of IBPA admitted to the respiratory intensive care unit (RICU) in the First Affiliated Hospital of Xinjiang Medical University from June 2014 to June 2022, and those who were primarily infected with other pathogens (such as bacteria, Mycobacterium tuberculosis) at admission were excluded. Whether the antifungal treatment was initiated or not on the basis of the bedside B-ROSE, the B-ROSE was administered as soon as possible within 24 hours after admission to RICU. The current international definition of invasive aspergillosis was used as the gold diagnostic standard, the diagnostic accordance rate, the sensitivity and specificity of B-ROSE were calculated respectively, and the receiver operator characteristic curve (ROC curve) was also plotted, to evaluate the predictive value in diagnosing IBPA. RESULTS: A total of 176 patients with severe pneumonia suspected of IBPA were included in the study. According to international diagnostic standards, there were 81 cases of IBPA and 95 cases of non-IBPA. According to the early diagnosis of B-ROSE, there were 89 cases of IBPA and 87 cases of non-IBPA. The diagnostic accordance rate of B-ROSE was 84.09% (148/176), the area under the ROC curve for B-ROSE in diagnosing severe IBPA was 0.844, the 95% confidence interval (95%CI) was 0.782-0.905, the sensitivity was 87.65%, the specificity was 81.05%, the positive predictive value was 79.78%, the negative predictive value was 88.51%, the rate of underdiagnosis was 12.35% (10/81), and the rate of misdiagnosis was 18.95% (18/95). Compared with the true negative group, the proportion of long-term (≥ 14 days) use of glucocorticoid [70.0% (7/10) vs. 9.1% (7/77), P < 0.01] and the proportion of cases with diabetes [40.0% (4/10) vs. 10.4% (8/77), P < 0.05] were significantly higher in the false negative group (underdiagnosis group). However, B-ROSE of both groups showed mucosal bleeding, congestion and edema [100.0% (10/10) vs. 94.8% (73/77), P > 0.05], indicating that acute mucosal inflammation was non-characteristic. Compared with the true positive group, the proportion of long-term (≥ 14 days) use of glucocorticoid in the false positive group (misdiagnosis group) was significantly reduced [33.3% (6/18) vs. 60.6% (43/71), P < 0.05]. The B-ROSE results showed the proportion of cases with mucosal white spots, black plaques and pseudomembrane was significantly reduced [16.7% (3/18) vs. 52.1% (37/71), P < 0.01] in the misdiagnosed group, which suggest that cases of long-term use of glucocorticoid and cases with B-ROSE showing mucosal white spots, black plaques and pseudomembrane were less likely to be misdiagnosed. The main diseases that were easily misdiagnosed as IBPA included pulmonary tuberculosis (38.9%, 7/18), inflammatory lung adenocarcinoma (27.8%, 5/18) and pulmonary vasculitis (16.7%, 3/18). CONCLUSIONS Before obtaining microbiological evidence, B-ROSE can assist in decision-making of early anti-aspergillus treatment for severe IBPA. This method is prompt, simple, and has high accuracy and reliability. If B-ROSE lacks characteristic manifestations, especially for severe pneumonia in patients with long-term use of glucocorticoid or diabetes, attention should be paid to the underdiagnosis of IBPA. Diseases such as lung tuberculosis, inflammatory lung adenocarcinoma and lung vasculitis should be vigilant against misdiagnosis as IBPA.
Humans ; Prospective Studies ; Antifungal Agents ; Glucocorticoids ; Rapid On-site Evaluation ; Reproducibility of Results ; Pulmonary Aspergillosis ; Pneumonia ; Diabetes Mellitus ; Adenocarcinoma of Lung ; Vasculitis ; Retrospective Studies