OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVE: To develop and validate a nomogram model for predicting 30-day mortality among elderly patients with sepsis-associated liver dysfunction (SALD), to identify high-risk patients and improve prognosis. METHODS: A retrospective cohort study was conducted using data extracted from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database for elderly patients with SALD who were first admitted to the intensive care unit (ICU) of Beth Israel Deaconess Medical Center between 2008 and 2019, including basic characteristics, severity scores, underlying diseases, infection foci, 24-hour vital signs, initial laboratory indicators, 24-hour complications, and prognosis related indicators. Patients were randomly assigned to training group and validation group in a ratio of 7 : 3. The training group used the LASSO regression analysis, as well as multivariate Logistic regression analysis to screen for independent risk factors for 30-day mortality. A nomogram prediction model was constructed, and receiver operator characteristic curve (ROC curve), calibration curves, and decision curve analysis (DCA) were used to evaluate the model, and validate the model using the validation cohort. RESULTS: A total of 630 elderly patients with SLAD were included in the study, including 441 in the training group and 189 in the validation group. Oxford acute severity of illness score (OASIS) for training group [odds ratio (OR) = 1.060, 95% confidence interval (95%CI) was 1.034-1.086], 24-hour pulse oxygen saturation (SpO₂; OR = 0.876, 95%CI was 0.797-0.962), initial mean corpuscular volume (MCV; OR = 1.043, 95%CI was 1.009-1.077), initial red blood cell distribution width (RDW; OR = 1.237, 95%CI was 1.123-1.362), initial blood glucose (OR = 1.008, 95%CI was 1.004-1.013), and initial aspartate aminotransferase (AST; OR = 1.000, 95%CI was 1.000-1.001) were independent risk factors for 30-day mortality in patients (all P < 0.05). Based on the above variables, a nomogram model was constructed, and the ROC curve showed that the area under the curve (AUC) of the model in the training group was 0.757 (95%CI was 0.712-0.803), with a sensitivity of 65.05% and a specificity of 74.90%; the AUC of the model in the validation group was 0.712 (95%CI was 0.631-0.792), with a sensitivity of 58.67% and a specificity of 81.58%. The calibration curves of the training and validation groups show that both the fitted curves were close to the standard curves. The Hosmer-Lemeshow test: the training group (χ ² = 6.729, P = 0.566), the validation group (χ ² = 13.889, P = 0.085), indicating that the model can fit the observed data well. The DCA curve shows that when the threshold probability of the training group was 16% to 94% and the threshold probability of the validation group was 27% to 99%, the net benefit of the model was good. CONCLUSIONS OASIS, 24-hour SpO₂, initial MCV, initial RDW, initial blood glucose and initial AST are independent risk factors for 30-day mortality in elderly patients with SALD. The nomogram based on these six variables demonstrates good predictive performance.
Humans ; Sepsis/complications* ; Retrospective Studies ; Nomograms ; Aged ; Prognosis ; Risk Factors ; Liver Diseases/mortality* ; Intensive Care Units ; ROC Curve ; Male ; Female ; Logistic Models

OBJECTIVE: Acupuncture therapies are known for their effectiveness in treating a variety of gastric diseases, although the mechanisms underlying these effects are not fully understood. This study tested the effectiveness of electroacupuncture (EA) at acupoints Zhongwan (RN12) and Weishu (BL21) for managing gastric motility disorder (GMD) and investigated the underlying mechanisms involved. METHODS: A GMD model was used to evaluate the impact of EA on various aspects of gastric function including the amplitude of gastric motility, electrogastrogram, food intake, and the rate of gastric emptying. Immunofluorescence techniques were used to explore the activation of spinal neurons by EA, specifically examining the presence of cholera toxin B subunit (CTB)-positive neurons and fibers emanating from acupoints RN12 and BL21. The stimulation of γ-aminobutyric acid (GABA)-ergic neurons in the spinal dorsal horn, the inhibition of sympathetic preganglionic neurons in the spinal lateral horn, and their collective effects on the activity of sympathetic nerves were examined. RESULTS: EA at RN12 and BL21 significantly improved gastric motility compromised by GMD. Notably, EA activated spinal neurons, with CTB-positive neurons and fibers from RN12 and BL21 being detectable in both the dorsal root ganglia and the spinal dorsal horn. Further analysis revealed that EA at these acupoints not only stimulated GABAergic neurons in the spinal dorsal horn but also suppressed sympathetic preganglionic neurons in the spinal lateral horn, effectively reducing excessive activity of sympathetic nerves triggered by GMD. CONCLUSION EA treatment at RN12 and BL21 effectively enhances gastric motility in a GMD model. The therapeutic efficacy of this approach is attributed to the activation of spinal neurons and the modulation of the spinal GABAergic-sympathetic pathway, providing a neurobiological foundation for the role of acupuncture in treating gastric disorders. Please cite this article as: Zhang MT, Liang YF, Dai Q, Gao HR, Wang H, Chen L, Huang S, Wang XY, Shen GM. A spinal neural circuit for electroacupuncture that regulates gastric functional disorders. J Integr Med. 2025; 23(1): 56-65.
Electroacupuncture ; Animals ; Male ; Acupuncture Points ; Stomach Diseases/physiopathology* ; Rats, Sprague-Dawley ; Gastrointestinal Motility ; Rats ; Gastric Emptying ; Neurons ; Spinal Cord ; Stomach/physiopathology*

Nigella sativa L. seeds have been traditionally utilized in Chinese folk medicine for centuries to treat vitiligo. This study revealed that the ethanolic extract of Nigella sativa L. (HZC) enhances melanogenesis and mitigates oxidative stress-induced cellular senescence and dysfunction in melanocytes. In accordance with established protocols, the ethanol fraction from Nigella sativa L. seeds was extracted, concentrated, and lyophilized to evaluate its herbal effects via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, tyrosinase activity evaluation, measurement of cellular melanin contents, scratch assays, senescence-associated β-galactosidase (SA-β-gal) staining, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis for expression profiling of experimentally relevant proteins. The results indicated that HZC significantly enhanced tyrosinase activity and melanin content while notably increasing the protein expression levels of Tyr, Mitf, and gp100 in B16F10 cells. Furthermore, HZC effectively mitigated oxidative stress-induced cellular senescence, improved melanocyte condition, and rectified various functional impairments associated with melanocyte dysfunction. These findings suggest that HZC increases melanin synthesis in melanocytes through the activation of the MAPK, PKA, and Wnt signaling pathways. In addition, HZC attenuates oxidative damage induced by H₂O₂ therapy by activating the nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway and enhancing the activity of downstream antioxidant enzymes, thus preventing premature senescence and dysfunction in melanocytes.
Oxidative Stress/drug effects* ; Melanocytes/cytology* ; Cellular Senescence/drug effects* ; Nigella sativa/chemistry* ; Plant Extracts/pharmacology* ; Seeds/chemistry* ; Mice ; Animals ; Melanins/metabolism* ; Monophenol Monooxygenase/metabolism* ; Humans

OBJECTIVE: CRISPR-Cas protects bacteria from exogenous DNA invasion and is associated with bacterial biofilm formation and pathogenicity. METHODS: We analyzed the type I-F CRISPR-Cas system of Legionella pneumophila WX48, including Cas1, Cas2-Cas3, Csy1, Csy2, Csy3, and Cas6f, along with downstream CRISPR arrays. We explored the effects of the CRISPR-Cas system on the in vitro growth, biofilm-forming ability, and pathogenicity of L. pneumophila through constructing gene deletion mutants. RESULTS: The type I-F CRISPR-Cas system did not affect the in vitro growth of wild-type or mutant strains. The biofilm formation and intracellular proliferation of the mutant strains were weaker than those of the wild type owing to the regulation of type IV pili and Dot/Icm type IV secretion systems. In particular, Cas6f deletion strongly inhibited these processes. CONCLUSION The type I-F CRISPR-Cas system may reduce biofilm formation and intracellular proliferation in L. pneumophila.
Legionella pneumophila/pathogenicity* ; CRISPR-Cas Systems ; Biofilms/growth & development* ; Phenotype ; Bacterial Proteins/metabolism* ; Gene Deletion

ObjectiveTo evaluate the application of prostate-specific membrane antigen （PSMA）PET/CT in prostate biopsy screening， and propose effective strategies for prostate biopsy decision making based on PSMA PET/CT detection. MethodsA retrospective analysis was conducted on PSMA PET/CT imaging and clinical pathological data from 155 patients with suspected prostate cancer between January 2020 and December 2023. PRIMARY score was used as the standardized evaluation method for PSMA PET/CT in the diagnosis of prostate cancer. And compared the positive prostate biopsy rates， missed diagnosis rates and biopsy reduction rates were compared regarding different PRIMARY scores. Receiver operating characteristic （ROC） curves were used to analyze prostate-specific antigen （PSA） and its derived parameters and identify the most suitable supplementary screening indicators for combined use with the PRIMARY score. ResultsAmong patients with PRIMARY scores of 1 to 5， the proportions of patients diagnosed with prostate cancer were 15.8% （3/19）， 17.1% （7/41）， 50% （12/24）， 95.2% （20/21） and 98% （49/50）， respectively. Using PRIMARY score of 3-5 as the biopsy screening strategy resulted in a positive prostate biopsy rate of 85.3% and biopsy reduction rate of 38.7%， but a missed diagnosis rate of 11%. PSA density > 0.15 ng/（mL·cm³） was selected as a supplementary screening criterion to detect prostate cancer from patients with PRIMARY scores of 1-2. The combined application of the above two screening criteria reduced the missed diagnosis rate to 2.2%. ConclusionThis study proposes a novel biopsy screening strategy for suspected prostate cancer patients using PSMA PET/CT， that is， a PRIMARY score of 3-5 or a PRIMARY score of 1-2 but PSA density>0.15 ng/（mL·cm³）， which can effectively avoid unnecessary biopsies and significantly reduce the missed diagnosis rate.

Objective Low-density lipoprotein cholesterol(LDL-C)is causally associated with atherosclerotic cardiovascular disease(ASCVD).Proprotein convertase subtilisin/kexin type 9(PCSK9)increases the degradation of low-density lipoprotein receptor(LDL-R),thereby promoting lipid accumulation.This study investigated the mechanism of microRNA(miRNA)-125a-5p in regulating PCSK9 transcriptional expression and lipid accumulation through histone deacetylase sirtuin 6(SIRT6)-mediated histone acetylation.Methods RAW264.7 macrophages exposed to oxidized low-density lipoprotein(ox-LDL)were used to establish a macrophage lipid accumulation model.The cells were divided into eight groups:control group(Group A),ox-LDL group(Group B),SIRT6 agonist group(Group C),si-SIRT6 group(Group D),miR-125a-5p mimic group(Group E),miR-125a-5p mimic negative control group(Group F),miR-125a-5p inhibitor group(Group G),and miR-125a-5p inhibitor negative control group(Group H).Oil red O staining was used to verify lipid ac-cumulation in macrophages.Real-time fluorescent quantitative polymerase chain reaction(PCR)was employed to detect the gene expression levels of miR-125a-5p,SIRT6 and PCSK9.Western blotting was used to detect the protein expression levels of SIRT6,histone 3 lysine 9 acetylation(H3K9ac),histone 3(H3),and PCSK9.An LDL-C kit was used to measure cellular LDL-C con-tent.Results Compared with Group A,Group B exhibited increased relative gene expression of miR-125a-5p,decreased relative SIRT6 gene and its protein expression,increased H3K9ac/H3 rati-o,increased relative gene and protein expression of PCSK9,and elevated LDL-C levels,with statis-tically significant differences(P＜0.01).In Group B,a positive correlation was observed between H3K9ac and PCSK9 protein expression(r=0.935 0,P＜0.01),as well as between PCSK9 and LDL-C(r=0.981 3,P＜0.01).Compared with Group B,Group C showed no significant change in miR-125a-5p expression(P＞0.05),but increased relative SIRT6 gene and its protein expres-sion,decreased H3K9ac/H3 ratio,decreased relative gene and protein expression of PCSK9,and reduced LDL-C levels(P＜0.01).In contrast,Group D,compared with Group B,had no signifi-cant change in miR-125a-5p gene expression(P＞0.05),but decreased relative gene and protein expression of SIRT6,increased H3K9ac/H3 ratio,increased relative PCSK9 gene and its protein expression,and elevated LDL-C levels(P＜0.05 or P＜0.01).Group E,compared with Group B,showed increased relative gene expression of miR-125a-5p,decreased relative SIRT6 gene and its protein expression,increased H3K9ac/H3,increased relative PCSK9 gene and its protein ex-pression,and elevated LDL-C levels(P＜0.01).Group G,compared with Group B,had de-creased relative gene expression of miR-125a-5p,increased relative gene and protein expression of SIRT6,decreased H3K9ac/H3 ratio,decreased relative PCSK9 gene and protein expression,and reduced LDL-C levels(P＜0.01).No significant changes were observed in miR-125a-5p,SIRT6,H3K9ac/H3 ratio,PCSK9,or LDL-C levels in Groups F and H compared with Group B(P＞0.05).Conclusion Epigenetics is an important regulatory mechanism in the development of ather-osclerosis(AS).Elevated LDL-C is a significant risk factor for AS,and increased PCSK9 expres-sion exacerbates lipid accumulation.Imbalance in histone acetylation is a novel mechanism involved in PCSK9-mediated lipid accumulation,potentially serving as an early detection marker for lipid me-tabolism disorders.SIRT6 acts as a protective factor by reversibly regulating PCSK9 transcriptional expression,reducing lipid accumulation,and delaying AS progression.MiR-125a-5p,as an up-stream regulatory gene of SIRT6,targets and inhibits SIRT6 transcription,thereby modulating his-tone acetylation,and may serve as a new target for early screening and prevention of dyslipidemia.

At present, the cause of traditional Chinese medicine(TCM) in China has entered a new period of high-quality development. How to strengthen the foundation for the TCM industry from the source is an important issue that deserves the attention of the authorities, industry, and academia. This study systematically analyzed the regulatory system of TCM raw materials and preparations. The study took the TCM industry chain and the product life cycle as a clue and focused on the dimensions of TCM resource protection and plant cultivation(farming), production and quality supervision of TCM raw materials and preparations, and their market access and distribution. It analyzed the current situation of the regulation of TCM raw materials and preparations under the regulatory system of drugs, discussed the main problems, and put forward corresponding suggestions. The results can provide an important reference value for the subsequent improvement of the regulatory system of drugs and the construction of a prominent regulatory system of drugs in accordance with TCM characteristics.
Drugs, Chinese Herbal/economics* ; Medicine, Chinese Traditional/standards* ; China ; Quality Control ; Humans ; Plants, Medicinal/chemistry*

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

OBJECTIVE: To review the latest research advancements in surgical techniques for the treatment of limb lymphedema. METHODS: The relevant literature at home and abroad in recent years was extensively reviewed, and the research on the treatment of limb lymphedema by surgical techniques were summarized and analyzed. RESULTS: Lymphovenous anastomosis has demonstrated good effectiveness for early to mid-stage limb lymphedema, however its long-term effectiveness and applicability for late-stage limb lymphedema still require further validation. Autologous lymphatic/venous grafting has shown clinical feasibility in the treatment of secondary limb lymphedema. Research on tissue-engineered lymphatic scaffolds remains insufficient, primarily due to the complexity of lymphatic anatomical structures and the technical challenges involved. Nevertheless, its potential application is promising. Vascularized lymph node flap transplantation has shown significant effectiveness in treating limb lymphedema, particularly yielding good outcomes in upper limb cases. However, it can not guarantee a complete cure for the condition. Charles' operation is the most effective treatment option for patients with late-stage limb lymphedema, but its extensive incision and severe postoperative complications limit its application. Liposuction has the advantages such as minimal invasiveness, high safety, and repeatability. It is suitable for patients with late-stage limb lymphedema who have failed conservative treatment or developed adiposity. However, its effectiveness is limited in patients with significant limb fibrosis. CONCLUSION Current treatments for limb lymphedema require further improvement, and there is considerable debate regarding treatment strategies for different stages of the condition. Future high-quality, multi-system combined treatment approaches are anticipated to guide clinical practice.
Humans ; Lymphedema/surgery* ; Surgical Flaps/blood supply* ; Lymphatic Vessels/surgery* ; Anastomosis, Surgical/methods* ; Lymph Nodes/transplantation* ; Lipectomy/methods* ; Extremities/surgery* ; Treatment Outcome ; Tissue Engineering ; Tissue Scaffolds ; Veins/transplantation*