Ten ursolic acid derivatives were designed from the lead compound ursolic acid by introducing 1,2,3-triazole at C-3 and C-28. The target compounds were synthesized and characterized by ¹H NMR and ¹³C NMR. MTT assay was used to study the antitumor activity of these compounds in human cancer cells with high expression (MCF-7 and SGC-7901). The results showed that the antitumor activity of all compounds on MCF-7 and SGC-7901 tumor cells was significantly higher than that of ursolic acid. The compound II₄ exhibited significant antitumor activity which was equivalent to the positive control drug nilotinib, molecular docking showed that the compound II₄ have high binding ability with c-Kit, which deserves further research.

BACKGROUND: While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients. METHODS: This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively. RESULTS: The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge. CONCLUSION Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans ; Retrospective Studies ; Male ; Length of Stay/statistics & numerical data* ; Female ; Middle Aged ; Adult ; Psychological Distress ; Inpatients/psychology* ; Aged ; Anxiety/diagnosis* ; Depression/diagnosis*

OBJECTIVE: To explore the functional rehabilitation of patients with rheumatoid arthritis (RA) after total knee arthroplasty (TKA). METHODS: A retrospective analysis was conducted on 101 patients who needed TKA due to rheumatoid arthritis (RA) involving both knees from January 2017 to December 2020, including 16 males and 85 females, aged from 41 to 65 years old with an average of (58.13±5.53) years old;body mass index (BMI) ranged from 16.88 to 33.33 kg·m^-2 with an average of (23.16±3.49) kg·m^-2;63 patients with grade 1, 29 patients with grade 2, and 9 patients with grade 3 according to classification of American Society of Anesthesiologists (ASA). According to the latest follow-up results at 12 months after operation, 82 patients returned to work and 19 patients did not return to work. Visual analogue scale(VAS) was used to evaluate the degree of pain relief before operation and 12 months after operation, and work, osteoarthritis and joint replacement questionnaire (WORQ) was used to evaluate knee joint activity status of all patients before and after operation, and the working ability index was used to evaluate working ability of all patients before operation and 12 months after operation. For the 82 patients who returned to work, the labor time stopped before operation and within 12 months after operation was compared, and the changes in labor grades, types of work and labor hours of patients before and after operation were recorded. For the 19 patients who did not return to work, the specific reasons for their non-return to work was analyzed;the postoperative satisfaction of patients was evaluated by using Likert satisfaction scale. All patients were followed up for at least 12 months. VAS was decreased from (6.49±0.59) before operation to (1.10±0.43) at 12 months after operation (P<0.05);for WORQ questionnaire survey, scores of walking, sitting posture, standing and stair climbing were increased from (1.07±0.35), (1.05±0.29), (1.06±0.34) and (1.14±0.42) before operation to (3.00±0.00), (2.87±0.33), (2.95±0.21) and (2.95±0.21) after operation, respectively, had statistically significant (P<0.05);the labor work index of all patients increased from 1.11±0.46 before operation to 2.99±0.10 at 12 months after operation, and the difference was statistically significant (P<0.05). Among the 82 patients who returned to work after operation, regarding the time of stopping labor, 81 patients stopped working within 3 months before operation, 1 patient stopped working for 4 to 6 months after operation, and the number of patients who stopped working was 81, 1, and 0 respectively. Forty patients returned to work within 3 months after operation, 4 to 6 months after operation for 29 patients, and 12 months after operation for 13 patients. 95.1% (78/82) of patients engaged in light labor before operation, and 85.4% (70/82) of patients engaged in moderate labor after operation. At 12 months after operation, the types of jobs and working hours available to all patients increased compared with those before operation. Among 19 patients who did not return to work after TKA, 7 patients had poor control of rheumatoid arthritis, 5 patients still felt pain, swelling and numbness on knee joint, 2 patients had retired, and 5 patients had other reasons. Eighty-six patients (85%) expressed great satisfaction with the postoperative working ability, 8 patients (8%) expressed satisfaction with the postoperative working ability, 6 patients (6%) expressed acceptance of postoperative working ability, and 1 patient (1%) expressed dissatisfaction with postoperative working ability. CONCLUSION TKA is an effective treatment option for patients with RA. After undergoing TKA, patients could significantly improve pain and functional activities of knee joint, and effectively enhance the quality of life and working ability. For patients whose rehabilitation labor capacity is not fully met, postoperative management and personalized rehabilitation treatment need to be strengthened to achieve the best rehabilitation effect.
Humans ; Female ; Male ; Arthroplasty, Replacement, Knee/rehabilitation* ; Arthritis, Rheumatoid/physiopathology* ; Middle Aged ; Aged ; Retrospective Studies ; Adult

OBJECTIVE: To investigate the short-term efficacy and safety of low-dose venetoclax combined with CHG (cytarabine+homoharringtonine+G-CSF) priming regimen in patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy. METHODS: The data of 14 patients with AML or high-risk MDS admitted to the department of hematology/oncology of the First Hospital of Tsinghua University and 2 cooperative institutions from July 2022 to August 2023 were retrospectively analyzed. All the patients were treated with low-dose venetoclax combined with CHG priming regimen and the early induction (one course) efficacy and adverse reactions were observed. RESULTS: Among the 14 patients, 10 were males and 4 were females, with a median age of 69.5 (46-83) years. After 1 cycle of induction chemotherapy, the complete remission (CR) rate was 64.3% (9/14) and overall response rate (ORR) was 78.6% (11/14). Among the 10 patients with adverse prognosis according to cytogenetics and molecular genetics, the CR rate was 50.0% (5/10), and ORR was 70.0% (7/10). In 7 patients with TP53 mutation, the CR rate was 42.9% (3/7) and ORR was 71.4% (5/7). In the 6 patients with complex karyotype, CR rate was 33.3% (2/6) and ORR was 66.7% (4/6). While the CR rate and ORR of 8 non-complex karyotype patients were both 87.5% (7/8), and the difference in CR rate between patients with complex karyotype and non-complex karyotype was statistically significant ( P < 0.05). The adverse reactions of chemotherapy were tolerable, without early treatment-related deaths. CONCLUSION Low-dose venetoclax combined with CHG priming regimen can be used as an effective treatment for AML and high-risk MDS patients who are ineligible for intensive chemotherapy, and it is safe and worthy of clinical application.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Aged ; Male ; Female ; Sulfonamides/therapeutic use* ; Middle Aged ; Myelodysplastic Syndromes/drug therapy* ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Aged, 80 and over ; Retrospective Studies ; Cytarabine/administration & dosage* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Homoharringtonine/therapeutic use*

OBJECTIVE: To investigate the clinical features and prognosis of central nervous system (CNS) invasion in peripheral T-cell lymphoma (PTCL) and construct a risk prediction model for CNS invasion. METHODS: Clinical data of 395 patients with PTCL diagnosed and treated in the First Affiliated Hospital of Zhengzhou University from 1st January 2013 to 31st December 2022 were analyzed retrospectively. RESULTS: The median follow-up time of 395 PTCL patients was 24(1-143) months. There were 13 patients diagnosed CNS invasion, and the incidence was 3.3%. The risk of CNS invasion varied according to pathological subtype. The incidence of CNS invasion in patients with anaplastic large cell lymphoma (ALCL) was significantly higher than in patients with angioimmunoblastic T-cell lymphoma (AITL) (P <0.05). The median overall survival was significantly shorter in patients with CNS invasion than in those without CNS involvement, with a median survival time of 2.4(0.6-127) months after diagnosis of CNS invasion. The results of univariate and multivariate analysis showed that more than 1 extranodal involvement (HR=4.486, 95%CI : 1.166-17.264, P =0.029), ALCL subtype (HR=9.022, 95%CI : 2.289-35.557, P =0.002) and ECOG PS >1 (HR=15.890, 95%CI : 4.409-57.262, P <0.001) were independent risk factors for CNS invasion in PTCL patients. Each of these risk factors was assigned a value of 1 point and a new prediction model was constructed. It could stratify the patients into three distinct groups: low-risk group (0-1 point), intermediate-risk group (2 points) and high-risk group (3 points). The 1-year cumulative incidence of CNS invasion in the high-risk group was as high as 50.0%. Further evaluation of the model showed good discrimination and accuracy, and the consistency index was 0.913 (95%CI : 0.843-0.984). CONCLUSION The new model shows a precise risk assessment for CNS invasion prediction, while its specificity and sensitivity need further data validation.
Humans ; Lymphoma, T-Cell, Peripheral/pathology* ; Prognosis ; Retrospective Studies ; Central Nervous System Neoplasms/pathology* ; Neoplasm Invasiveness ; Male ; Female ; Central Nervous System/pathology* ; Middle Aged ; Adult

OBJECTIVE: To investigate the significance of serum β₂-microglobulin (β₂-MG) for survival and relapse of patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era. METHODS: Clinical data of 92 patients with DLBCL admitted from December 2003 to July 2015 were retrospectively analyzed. The optimal cutoff value of β₂-MG levels for predicting prognosis of the DLBCL patients was determined using receiver operating characteristic (ROC) curve. KaplanMeier analysis was used to estimate progression-free survival (PFS) and overall survival (OS). Cox logistic regression analysis was used to explore potential prognostic factors associated with survival. Binary logistic regression analysis was used to analyze the relationship between various factors and relapse. RESULTS: The most discriminative cutoff value for β₂-MG level was determined to be 2.25 mg/L by the ROC curve. Subgroup analysis showed that patients in the elevated β₂-MG (＞2.25 mg/L) group had significantly worse PFS(P =0.006) and a trend toward worse OS compared with those in the low β₂-MG (≤2.25 mg/L) group(P =0.053). Univariate analysis showed that elevated β₂-MG, age>60 years, Ann Arbor stage III-IV, as well as IPI score ≥3 were associated with worse PFS. Binary logistic regression analysis showed that age＞60 years and β₂-MG＞2.25 mg/L were potential influencing factors for relapse of DLBCL patients. CONCLUSION Serum β ₂-MG might be an important predictor for the survival and relapse of DLBCL patients in the rituximab era.
Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; beta 2-Microglobulin/blood* ; Rituximab ; Retrospective Studies ; Prognosis ; Female ; Male ; Middle Aged ; Recurrence ; ROC Curve

OBJECTIVE: To investigate the therapeutic potential of pseudolaric acid B (PAB) on non-alcoholic fatty liver disease (NAFLD) and its underlying molecular mechanism in vitro and in vivo. METHODS: Eight-week-old male C57BL/6J mice (n=32) were fed either a normal chow diet (NCD) or a high-fat diet (HFD) for 8 weeks. The HFD mice were divided into 3 groups according to a simple random method, including HFD, PAB low-dose [10 mg/(kg·d), PAB-L], and PAB high-dose [20 mg/(kg·d), PAB-H] groups. After 8 weeks of treatment, glucose metabolism and insulin resistance were assessed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Biochemical assays were used to measure the serum and cellular levels of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). White adipose tissue (WAT), brown adipose tissue (BAT) and liver tissue were subjected to hematoxylin and eosin (H&E) staining or Oil Red O staining to observe the alterations in adipose tissue and liver injury. PharmMapper and DisGeNet were used to predict the NAFLD-related PAB targets. Peroxisome proliferator-activated receptor alpha (PPARα) pathway involvement was suggested by Kyoto Encyclopedia of Genes and Genomes (KEGG) and search tool Retrieval of Interacting Genes (STRING) analyses. Luciferase reporter assay, cellular thermal shift assay (CETSA), and drug affinity responsive target stability assay (DARTS) were conducted to confirm direct binding of PAB with PPARα. Molecular dynamics simulations were applied to further validate target engagement. RT-qPCR and Western blot were performed to assess the downstream genes and proteins expression, and validated by PPARα inhibitor MK886. RESULTS: PAB significantly reduced serum TC, TG, LDL-C, AST, and ALT levels, and increased HDL-C level in HFD mice (P<0.01). Target prediction analysis indicated a significant correlation between PAB and PPARα pathway. PAB direct target binding with PPARα was confirmed through luciferase reporter assay, CETSA, and DARTS (P<0.05 or P<0.01). The target engagement between PAB and PPARα protein was further confirmed by molecular dynamics simulations and the top 3 amino acid residues, LEU321, MET355, and PHE273 showed the most significant changes in mutational energy. Subsequently, PAB upregulated the genes expressions involved in lipid metabolism and mitochondrial biogenesis downstream of PPARα (P<0.05 or P<0.01). Significantly, the PPARα inhibitor MK886 effectively reversed the lipid-lowering and PPARα activation properties of PAB (P<0.05 or P<0.01). CONCLUSION PAB mitigates lipid accumulation, ameliorates liver damage, and improves mitochondrial biogenesis by binding with PPARα, thus presenting a potential candidate for pharmaceutical development in the treatment of NAFLD.
Animals ; PPAR alpha/metabolism* ; Non-alcoholic Fatty Liver Disease/pathology* ; Male ; Mice, Inbred C57BL ; Lipid Metabolism/drug effects* ; Diterpenes/therapeutic use* ; Organelle Biogenesis ; Diet, High-Fat ; Humans ; Mice ; Liver/metabolism* ; Insulin Resistance ; Mitochondria/metabolism* ; Molecular Docking Simulation

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*