Objective:To detect the expression of autophagy-related genes (ATGs) involved in the late stage of autophagy in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS), analyze the difference and explore its possible clinical significance.Methods:① Peripheral blood specimens and clinical data were collected from 90 AS patients (AS group) who attended the outpatient clinic of the Department of Rheumatology and Immunology of the Affiliated Hospital of North Sichuan Medical College from March 2022 to August 2023, among which 30 patients were treated with secukinumab monoclonal antibody for 24 weeks (the treatment group), and clinical data and peripheral blood specimens from 45 healthy individuals (the HC group) who had medical checkups in the Affiliated Hospital of Chuanbei Medical College during the same period were used as the control group. As the control group, the mRNA expression levels of six ATGs (ATG5, ATG7, LC3-Ⅱ, ATG4B, ATG2A, ATG10) involved in the late autophagy stage were detected in PBMCs of peripheral blood specimens by RT-qPCR, and were compared among different groups, and the measured data conformed to the normal distribution were analyzed using the paired t-test, and the abnormal distribution date were analyzed using the Wilcoxon signed-rank test. Wilcoxon signed-rank test was used for measurement data, and Spearman correlation analysis was used for correlation analysis. ② Receiver operating curve (ROC) was used to verify the difference in the expression of ATGs in the late stage of autophagy between AS group and HC group to evaluate its value in the diagnosis of AS and the inflammatory state of the disease. Results:① Compared with the HC group, ATG2A [2.00(1.10, 2.70)×10 -3, 7.50(4.60, 10.0)×10 -3, Z=-6.67, P<0.001], ATG5 [3.60 (2.30, 5.30)×10 -3, 7.20(5.50, 9.20)×10 -3, Z=-3.63, P=0.001], LC3Ⅱ[25.70(8.50, 35.00)×10 -3, 52.20(45.00, 69.10)×10 -3, Z=-5.87, P<0.001] and ATG7[5.50(3.20, 8.10)×10 -3, 8.30(5.20, 9.80)×10 -3, Z=-2.38, P=0.017] the mRNA expressions were significantly decreased in the AS group. ②ATG5 mRNA expression was negatively correlated with platelet count ( r=-0.35, P=0.008), LC3-Ⅱ was negatively correlated with estimated glomerular filtration rate ( r=-0.33, P=0.017), ATG7 was positively correlated with absolute basophil count ( r=0.33, P=0.011),ATG10 was negatively correlated with estimated glomerular filtration rate and C-reactive protein (CRP) was negatively correlated ( r=-0.30, P=0.032). ③ The area under the ROC curve (AUC) of ATG2A mRNA expression level for predicting AS was 0.910, and the sensitivity and specificity were 94.6% and 83.8% respectively. ④ After 24 weeks of treatment with secukinumab, the mRNA expression levels of ATG2A[2.00(1.20, 2.90)×10 -3, 4.90(0.10, 7.40)×10 -3, Z=-3.75, P<0.001] and LC3-Ⅱ[2.00(1.20, 2.90)×10 -3, 4.90(0.10, 7.40)×10 -3, Z=-3.75, P<0.001]were elevated in the AS patients. Conclusion:Late autophagy-related genes ATG2A, ATG5, LC3II, ATG7 may be involved in AS development.The AUC of ATG2A in AS is 0.91, suggesting that ATG2a is expected to be a biological indicator for early diagnosis of AS. Secukinumab may be involved in the regulation of autophagy by affecting the expression of late autophagy genes, but the specific mechanism needs to be further explored.

OBJECTIVE: The present study evaluated the effects of deep acupuncture at Weizhong acupoint (BL40) on bladder function and brain activity in a rat model of overactive bladder (OAB), and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture. METHODS: Adult female Sprague-Dawley rats were randomly divided into six groups, comprising a control group, model group, group treated with deep acupuncture at BL40, group treated with shallow acupuncture at BL40, group treated with acupuncture at non-acupoint next to BL40, and group treated with acupuncture at Xuanzhong (GB39). Urodynamic evaluation was used to observe the urination, and functional magnetic resonance imaging was used to observe the brain activation. The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay, and the mechanism was verified by stabilizing mast cells (MCs) or blocking tibial nerve. RESULTS: Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex (M1), periaquaductal gray matter (PAG), and pontine micturition center (PMC). It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC. Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes. Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine, substance P, and histamine in the tissues around BL40. Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats. CONCLUSION Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve, thereby regulating the activation of the brain area that controls the lower urinary tract. Please cite this article as: Liu X, Zhang CY, Du XY, Li SS, Wang YQ, Zheng Y, Deng HZ, Fang XQ, Li JY, Wang ZQ, Xu SF, Mi YQ. Acupuncture at Weizhong (BL40) attenuates acetic acid-induced overactive bladder in rats by regulating brain neural activity through the modulation of mast cells and tibial nerves. J Integr Med. 2025; 23(1): 46-55.
Animals ; Urinary Bladder, Overactive/physiopathology* ; Mast Cells/physiology* ; Rats, Sprague-Dawley ; Female ; Acupuncture Therapy ; Acupuncture Points ; Rats ; Brain/physiopathology* ; Tibial Nerve/physiopathology* ; Acetic Acid ; Urinary Bladder/physiopathology*

Objective:To explore the correlation between the post-traumatic stress disorder(PTSD)level and postoperative fear disease progression and quality of life in patients undergoing laparoscopic myomectomy,and to analyze the related factors affecting the occurrence of PTSD in patients.Methods:120 patients who underwent laparoscopic myomectomy in Ruijin People's Hospital from April 2022 to April 2024 were selected,the PTSD occurrence was assessed with the Civilian version of PTSD checklist-civilian version(PCL-C)1 month after operation,and the progression of fear of Disease was assessed with the fear of progression questionnaire-short form(FoP-Q-SF),the quality of life was assessed with uterine fibroid symptoms and health-related quality of life questionnaire(UFS-QOL).The correlation between PTSD level and postoperative fear disease progression and quality of life in patients undergoing laparoscopic myomectomy was analyzed,and the factors of PTSD in patients undergoing laparoscopic myomectomy were analyzed by multivariate Logistic regression.Results:PTSD scores of in patients undergoing laparoscopic myomectomy was(36.93±5.69)score,fear of disease progression was(26.00±1.66)score,quality of life was(54.27±4.82)score.The total score of PCL-C was positively correlated with the total score of FoP-Q-SF,and negatively correlated with the total score of UFS-QOL(P＜0.05).The patients were divided into PTSD group(n=30)and non-PTSD group(n=90)according to whether or not occurrence of PTSD at 1 month after operation.Univariate analysis showed that,there were significant differences in age,education level,family income,number of fibroids,operation time and preoperative anxiety level between the PTSD group and the non-PTSD group(P＜0.05).Multivariate Logistic regression analysis showed that age ≥35 years old,operation time ≥90 min,preoperative anxiety level of moderate to severe,and increased total score of FoP-Q-SF were independent risk factors for PTSD in patients undergoing laparoscopic myomectomy(P＜0.05),and increased total score of UFS-QOL were protective factors(P＜0.05).Conclusion:The PTSD level in patients undergoing laparoscopic myomectomy is positively correlated with fear disease progression and negatively correlated with quality of life.Age,operation time,preoperative anxiety,fear disease progression and quality of life were the factors that influenced the occurrence of PTSD.

Objective To investigate the efficacy of an interpretable integrated learning model combining clinical indicators,CT image features and radiomics features for the differential diagnosis of lung squamous cell carcinoma and adenocarcinoma,so as to provide references for clincal treatment decisions.Methods A retrospective analysis was conducted on clinical and imaging data from 220 patients(231 lesions)with primary non-small cell lung cancer at Jiangjin Central Hospital of Chongqing(Center 1)and 83 patients(84 lesions)at Chongqing General Hospital(Center 2).In Center 1,the squamous cell carcinoma group consisted of 60 patients(60 lesions),while the adenocarcinoma group included 160 patients(171 lesions).In Center 2,the squamous cell carcinoma group comprised 18 patients(18 lesions),and the adenocarcinoma group involved 65 patients(66 lesions).The patients were categorized into squamous cell carcinoma and adenocarcinoma groups based on pathological findings.Center 1 was randomly partitioned into a training set and a validation set at a 7∶3 ratio,while Center 2 served as the independent test set.Firstly,a deep learning model,VB-Net,was used to automatically segment the tumor region on the lung window image;secondly,the SMOTE(synthetic minority oversampling technique)method was used to balance the categories in the training set and standardize the extracted features with Z-scores;thirdly,the least absolute shrinkage and selection operator(LASSO)were used to select the optimal radiomics features and calculate the radiomics score(Radscore),and univariate and multivariate logistic regression was used to screen clinical indicators and independent clinical factors for differentiating lung squamous cell carcinoma and adenocarcinoma in CT image features;finally,three ensemble learning algorithms(AdaBoost,Bagging decision tree and XGBoost)were used to combine independent clinical factors and Radscore to construct the model.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic performance of the models.SHAP technique was used to analyze the feature contribution and model decision-making process.Results Among the evaluated ensemble models,AdaBoost and Bagging decision trees demonstrated overfitting tendencies.In contrast,the XGBoost model showed the best performance,achieving AUC values of 0.939,0.887 and 0.853 in the training,validation and independent test sets,respectively.SHAP indicated that Radscore was the most important feature affecting the performance of the model.The decision diagram enabled the visualization of the diagnostic process of the model.Conclusion The interpretable integrated learning model based on clinical indicators,CT image and radiomics features is expected to non-invasively diagnose lung squamous cell carcinoma and adenocarcinoma before treatment and assist clinicians make treatment decisions as early as possible.[Chinese Medical Equipment Journal,2025,46(7):12-20]

Objective:To analyze the research progress and hotspots of clinical pathway informatization at home and abroad, and provide references and guidance for the construction of clinical pathway informatization in China.Methods:The relevant literature on clinical pathway informatization research were retrieved from China National Knowledge Infrastructure and Web of Science databases, which were published from January 1, 2000 to July 20, 2023. Bibliometric and thematic analysis methods were used to analyze the commonalities and differences in annual publication volume, high-frequency author collaboration networks, high-frequency keywords, and research hotspots of domestic and foreign literature.Results:This study included a total of 257 domestic literature and 174 foreign literature. The number of domestic publications had gradually increased since 2005, with the highest number in 2012 and a significant downward trend after 2015; The overall number of foreign publications was on the rise. Domestic high-frequency authors mostly came from medical institutions, while foreign high-frequency authors were mainly concentrated in universities and research institutes, and both had formed author collaboration networks. However, the research continuity of foreign authors were better than that of domestic authors. There were commonalities in the electronicization and semantics of clinical pathways, process design and management, disease management, and clinical decision support in relevant research hotspots at home and abroad, but there were significant differences in system integration, process design, pathway analysis, and disease management. Foreign related researches had the advantages of leading technology.Conclusions:There were certain similarities and differences in the research topics of clinical pathway informatization at home and abroad, and relevant studies abroad had shown certain frontiers in the application of new technologies. In the future, China should learn from international advanced experience, utilize emerging technologies such as machine learning and big language models, strengthen patient-centered, promote the precise and intelligent development of clinical pathway management, and improve the quality of medical services.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

This study aims to investigate the molecular mechanism by which naringin alleviates cerebral ischemia/reperfusion(CI/R) injury through DRP1/LRRK2/MCU signaling axis. A total of 60 SD rats were randomly divided into the sham group, the model group, the sodium Danshensu group, and low-, medium-, and high-dose(50, 100, and 200 mg·kg~(-1)) naringin groups, with 10 rats in each group. Except for the sham group, a transient middle cerebral artery occlusion/reperfusion(tMCAO/R) model was established in SD rats using the suture method. Longa 5-point scale was used to assess neurological deficits. 2,3,5-Triphenyl tetrazolium chloride(TTC) staining was used to detect the volume percentage of cerebral infarction in rats. Hematoxylin-eosin(HE) staining and Nissl staining were employed to assess neuronal structural alterations and the number of Nissl bodies in cortex, respectively. Western blot was used to determine the protein expression levels of B-cell lymphoma-2 gene(Bcl-2), Bcl-2-associated X protein(Bax), cleaved cysteine-aspartate protease-3(cleaved caspase-3), mitochondrial calcium uniporter(MCU), microtubule-associated protein 1 light chain 3(LC3), and P62. Mitochondrial structure and autophagy in cortical neurons were observed by transmission electron microscopy. Immunofluorescence assay was used to quantify the fluorescence intensities of MCU and mitochondrial calcium ion, as well as the co-localization of dynamin-related protein 1(DRP1) with leucine-rich repeat kinase 2(LRRK2) and translocase of outer mitochondrial membrane 20(TOMM20) with LC3 in cortical mitochondria. The results showed that compared with the model group, naringin significantly decreased the volume percentage of cerebral infarction and neurological deficit score in tMCAO/R rats, alleviated the structural damage and Nissl body loss of cortical neurons in tMCAO/R rats, inhibited autophagosomes in cortical neurons, and increased the average diameter of cortical mitochondria. The Western blot results showed that compared to the sham group, the model group exhibited increased levels of cleaved caspase-3, Bax, MCU, and the LC3Ⅱ/LC3Ⅰ ratio in the cortex and reduced protein levels of Bcl-2 and P62. However, naringin down-regulated the protein expression of cleaved caspase-3, Bax, MCU and the ratio of LC3Ⅱ/LC3Ⅰ ratio and up-regulated the expression of Bcl-2 and P62 proteins in cortical area. In addition, immunofluorescence analysis showed that compared with the model group, naringin and positive drug treatments significantly decreased the fluorescence intensities of MCU and mitochondrial calcium ion. Meanwhile, the co-localization of DRP1 with LRRK2 and TOMM20 with LC3 in cortical mitochondria was also decreased significantly after the intervention. These findings suggest that naringin can alleviate cortical neuronal damage in tMCAO/R rats by inhibiting DRP1/LRRK2/MCU-mediated mitochondrial fragmentation and the resultant excessive mitophagy.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/genetics* ; Flavanones/administration & dosage* ; Rats ; Dynamins/genetics* ; Male ; Brain Ischemia/genetics* ; Protein Serine-Threonine Kinases/genetics* ; Signal Transduction/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage*

OBJECTIVE: Photodynamic therapy has become an important method in clinical tumor treatment. This study aimed to investigate the effects of hematoporphyrin on multiple myeloma (MM) and its potential applications. METHODS: The MM cell line RPMI 8226 was treated with hematoporphyrin derivative (HPD), and CCK-8 assay was used to determine cell viability, apoptosis was detected by flow cytometry, intracellular reactive oxygen species (ROS) levels were measured using a detection kit combined with flow cytometry, and Western blot assay was used to detect apoptosis-related proteins and key signaling pathway protein levels. RESULTS: The optimal incubation time for the maximum absorption of HPD in RPMI 8226 cells was 4 hours. HPD significantly inhibited the proliferation of RPMI 8226 cells in a dose- and illumination time-dependent manner ( r =0.981; r =0.961). Additionally, HPD induced apoptosis in RPMI 8226 cells, but had no significant inhibitory effect on peripheral blood mononuclear cells derived from healthy individuals. HPD combined with illumination treatment significantly increased the intracellular ROS level, upregulated the expression of apoptosis-related proteins such as cleaved PARP, cleaved caspase-3 and Bax, and down-regulated the expression of proteins that maintain cell survival, such as NF-κB and Akt. CONCLUSION The HPD can inhibit the proliferation and induce apoptosis of multiple myeloma cells.
Humans ; Multiple Myeloma/pathology* ; Hematoporphyrins/pharmacology* ; Apoptosis/drug effects* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Cell Proliferation/drug effects* ; Photochemotherapy ; Cell Survival/drug effects* ; Signal Transduction

OBJECTIVE: To investigate possible associations between physical function assessment scales, such as Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS), with all-cause mortality in acute decompensated heart failure (ADHF) patients. METHODS: A total of 108 ADHF patients were analyzed from October 2020 to October 2022, and followed up to May 2023. The association between baseline clinical characteristics and all-cause mortality was analyzed by univariate Cox regression analysis, while for SPPB and BBS, univariate Cox regression analysis was followed by receiver operating characteristic curves, in which the area under the curve represented their predictive accuracy for all-cause mortality. Incremental predictive values for both physical function assessments were measured by calculating net reclassification index and integrated discrimination improvement scores. Optimal cut-off value for BBS was then identified using restricted cubic spline plots, and survival differences below and above that cut-off were compared using Kaplan-Meier survival curves and the log-rank test. The clinical utility of BBS was measured using decision curve analysis. RESULTS: For baseline characteristics, age, female, blood urea nitrogen, as well as statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors, were predictive for all-cause mortality for ADHF patients. With respect to SPPB and BBS, higher scores were associated with lower all-cause mortality rates for both assessments; similar area under the curves were measured for both (0.774 for SPPB and 0.776 for BBS). Furthermore, BBS ≤ 36.5 was associated with significantly higher mortality, which was still applicable even adjusting for confounding factors; BBS was also found to have great clinical utility under decision curve analysis. CONCLUSIONS BBS or SPPB could be used as tools to assess physical function in ageing ADHF patients, as well as prognosticate on all-cause mortality. Moreover, prioritizing the improvement of balance capabilities of ADHF patients in cardiac rehabilitation regimens could aid in lowering mortality risk.

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*