OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy

OBJECTIVE: Glucocorticoid-induced osteoporosis (GIOP) is a common complication of prolonged glucocorticoid therapy. Chlorogenic acid (CGA), a polyphenol with antioxidant properties that is extracted from traditional Chinese medicines such as Eucommiae Cortex, has potential anti-osteoporotic activity. This study aimed to investigate the possible effects of CGA on GIOP in mice and murine long bone osteocyte Y4 (MLO-Y4) cells and explore the underlying molecular mechanisms. METHODS: The protective effects of CGA were initially evaluated in the GIOP mouse model induced by dexamethasone (Dex). The micro-computed tomography, hematoxylin-eosin staining, silver nitrate staining, and serum detection were used to assess the efficacy of CGA for improving bone formation in vivo. Then, network pharmacology analysis was used to predict the potential targets and molecular mechanisms underlying the therapeutic efficacy of CGA against GIOP. After that, 2',7'-dichlorofluorescein diacetate staining, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, and Western blotting were used to verify the mechanisms of CGA against GIOP in vitro. RESULTS: Animal experiments showed that CGA treatment effectively attenuated Dex-induced decreases in bone mass and strength and improved disrupted osteocyte morphology in mice. The protein-protein interaction analysis highlighted erb-b2 receptor tyrosine kinase (ERBB2), which is also known as human epidermal growth factor receptor 2 (HER2), caspase-3, kinase insert domain receptor, matrix metallopeptidase 9, matrix metallopeptidase 2, proto-oncogene tyrosine-protein kinase Src, and epidermal growth factor receptor as core targets. The Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched pathways (P < 0.05), including the ERBB, phosphoinositide 3 kinase-AKT serine/threonine kinase 1 (AKT), and mechanistic target of rapamycin kinase (mTOR) pathways. Cellular experiments verified that CGA enhanced bone formation and promoted autophagy while inhibiting apoptosis in MLO-Y4 cells exposed to Dex, which was associated with the upregulated expression of HER2 and activation of the HER2/AKT/mTOR signaling pathway. CONCLUSION CGA exerted anti-osteoporotic effects against GIOP, partially through targeting osteocytes and modulating the HER2/AKT/mTOR signaling pathway. Please cite this article as: Xie AN, Zhang SZY, Zhang Y, Cao JL, Wang CL, Wang LB, Wu HJ, Zhang J, Dai WW. Chlorogenic acid mitigates glucocorticoid-induced osteoporosis via modulation of HER2/AKT/mTOR signaling pathway. J Integr Med. 2025; 23(6):670-682.
Animals ; Chlorogenic Acid/therapeutic use* ; Osteoporosis/metabolism* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Mice ; Glucocorticoids/adverse effects* ; Receptor, ErbB-2/metabolism* ; Proto-Oncogene Mas ; Dexamethasone/adverse effects* ; Osteocytes/drug effects* ; Osteogenesis/drug effects* ; Male ; Cell Line ; Mice, Inbred C57BL ; Humans

Objective:To investigate the efficacy of lightroom therapy on depressive mood and sleep problems in patients with depression, and the potential effects on physiological indices related to circadian rhythms.Methods:From October 2021 to July 2023, 54 patients with acute-phase depression hospitalized in the Mental Health Center of the First Hospital of Hebei Medical University were recruited. The participants were randomly assigned to either medication combined with the bright light therapy group (bright light group, n=36) or medication combined with the dim light therapy group (dim light group, n=18). Both groups received light therapy for 2 weeks, at 10 000 lx in the bright light group and 300 lx in the dim light group. Both groups received 30 minutes of light therapy from 7:30-8:00 a.m daily over two weeks, followed up for 1 week post-treatment. The Hamilton Depression Rating Scale (HAMD 17) was used to assess patients′ depressive symptoms, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess patients′ sleep quality at baseline, at the end of every week. The 32-Item Hypomania Checklist (HCL-32) was used at the end of week 2 to assess the risk of manic switching after treatment. Daily measurements of body temperature, heart rate, and blood pressure were taken before and after light therapy, along with recording adverse events related to the therapy. Paired t- tests were used to compare changes in physiological indicators before and after treatment, and repeated measures ANOVA was applied to compare clinical symptom changes between the two groups. Results:Thirty-one and fifteen patients completed this study in the bright light and dim light groups, respectively, with no statistically significant difference in dropout rates( P>0.05). There were significant interaction effects between the time and group for HAMD 17 and PSQI score( F=5.51,4.11, both P<0.05). Both groups showed significant reductions in HAMD 17 and PSQI scores at baseline, week 1, week 2, and week 3 ( P<0.001). In the bright light group, body temperature increased significantly post-treatment on days 1-4, day 7, and day 12 (all P<0.05). Heart rate elevated on day 5 ( P<0.05).Systolic blood pressure decreased on days 4, 5, 11, and 12 compared to the pre-treatment baseline(all P<0.05). In the dim light group, systolic blood pressure increased on day 11 ( P<0.05). Diastolic blood pressure in the bright light group decreased on days 1, 5, and 6( P<0.05). No serious adverse events, vision loss, ocular structural changes occurred in either group. No hypomania or mania episodes were observed. The incidence of adverse events did not differ significantly ( P>0.05). Conclusion:Medication combined with indoor bright light is more effective than the combination of dim light for depressive symptoms and sleep problems in patients with depression. Patients receiving bright light also may exhibit a higher body temperature, accelerated heart rate, and reduced blood pressure.

Objective To investigate the effects of Bushen Shengjing Tiaohe Qixue Prescription on rats with diminished ovarian reserve(DOR)based on Wnt/β-catenin signaling pathway.Methods Totally 60 8-week-old SD female rats were randomly divided into control group,model group,estradiol valerate group and TCM low-,medium-and high-dosage groups,with 10 rats in each group.Except for the control group,the rats in the other groups were given a single intraperitoneal injection of cyclophosphamide 75 mg/kg to replicate the DOR rat model.From the next day of modeling,the corresponding drugs was administered for medication groups by gavage for 3 weeks.The general conditions of the rats were observed,ELISA was used to detect the contents of serum follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),anti-mullerian hormone(AMH)and inhibin B(INHB),HE staining was used to observe the morphologic changes in ovarian tissue,Western blot was used to detect GSK3β,β-catenin,CyclinD1 and c-MYC protein expressions in ovarian tissues,immunohistochemical staining was used to observe β-catenin expression in ovarian tissue,RT-qPCR was used to detect Wnt1,Wnt2,Wnt4,GSK3β,β-catenin,CyclinD1 and c-MYC mRNA expression in ovarian tissue,transmission electron microscopy was used to observe ultrapathologic structure of ovarian granulosa cells.Results Compared with the control group,the rats in the model group had reduced intake of food and water,slow or even reduced body mass gain,and disturbed estrous cycle,the serum contents of FSH and LH increased(P<0.01),the contents of E2,AMH and INHB decreased(P<0.01);the number of follicles of all levels in ovarian tissue was reduced,and there was increased number of atretic follicles with disturbed arrangement of the granulosa cells;the expression of GSK3β protein in ovarian tissue increased(P<0.01),the expression of β-catenin,CyclinD1 and c-MYC protein decreased(P<0.05,P<0.01),and β-catenin positive expression decreased(P<0.01),the expression of Wnt1,Wnt2,Wnt4,β-catenin,CyclinD1 and c-MYC mRNA in ovarian tissue decreased(P<0.01),GSK3β mRNA expression was increased(P<0,01);organelles such as mitochondria and nuclei of ovarian granulosa cells were highly swollen and partially lysed.Compared with the model group,the rats in the administered group all had different degrees of body mass increase,partial restoration of the motility cycle,serum FSH and LH contents decreased,and serum E2,AMH and INHB contents increased(P<0.01,P<0.05);the number of follicles at all levels in ovarian tissue increased to varying degrees,and the atretic follicles were reduced;the expression of GSK3β protein in ovarian tissue decreased,β-catenin,CyclinD1 and c-MYC protein expressions increased,β-catenin positive expression increased,the expression of Wnt1,Wnt2,Wnt4,β-catenin,CyclinD1 and c-MYC mRNA in ovarian tissue increased,and GSK3β mRNA expression decreased,with statistical significance in estradiol valerate group and TCM high-dosage group(P<0.05,P<0.01);mitochondria,endoplasmic reticulum and other organelles of ovarian granulosa cells were mildly to moderately swollen.Conclusion Bushen Shengjing Tiaohe Qixue Prescription can improve ovarian function and regulate serum sex hormone levels in DOR model rats,and its mechanism might be related to the activation of Wnt/β-catenin signaling pathway.

Objective To use AI-assisted motor dysfunction assessment for quantitative evaluation of motor function in Parkinson's disease(PD)and multiple system atrophy-Parkinsonian type(MSA-P)in order to achieve accurate differential diagnosis.Methods A total of 105 participants aged ≥60 years were consecutively enrolled from the First and Third Medical Centers of Chinese PLA General Hospital between January and September 2024.Based on diagnostic criteria,they were divided into a PD group(48 cases),a MSA-P group(31 cases),and a control group(26 cases).The general information was collected,and the motor function was evaluated with Move-ment Dysfunction Assessment Software in order to assess the diagnostic value of the AI-assisted assessment in differentiating between PD and MSA-P.Results Significantly differences were observed among the three groups in terms of facial expression indicators,bilateral finger tapping frequency,bilateral hand movement frequency,right hand movement amplitude change rate,bilat-eral palm flipping frequency,bilateral toe tapping frequency,freezing load of bilateral toe tapping,bilateral leg flexibility frequency,right leg flexibility amplitude change rate,freezing load of bilat-eral leg flexibility,upright extension angular velocity,turnaround time,forward step frequency,backward step frequency,forward average stride length,backward average stride length,forward average walking speed,backward average walking speed,forward average step width,backward average step width,bilateral postural tremor frequency,bilateral postural tremor maximum am-plitude,bilateral action tremor frequency,bilateral action tremor maximum amplitude,and com-parison of bilateral resting tremor frequency(P＜0.05,P＜0.01).The MSA-P group exhibited significantly lower blink frequency,maximum amplitude and frequency of facial tremors,upright extension angular velocity,and step frequency,while higher ratio of mouth opening duration and longer turnaround time when compared with the PD group(P＜0.05,P＜0.01).The AUC value of the combined nine motor function indicators and the five facial expression indicators in differ-entiating PD from MSA-P was 0.943(95％CI:0.895-0.991,P=0.000)and 0.925(95％CI:0.870-0.981,P=0.000),respectively,both better than that of individual indicators.Conclusion Combi-nation assessment of facial expression,posture,gait with AI assistance can contribute to the dif-ferential diagnosis of PD and MSA-P.

Objective:To analyze the value of 18F-FDG PET/CT combined with MRI in the diagnosis and differential diagnosis of ductal carcinoma in situ (DCIS) and early stage invasive ductal carcinoma (IDC). Methods:From September 2019 to December 2023, 12 patients with DCIS (all females; age 36-67 years) and 34 patients with early stage IDC (all females; age 36-73 years) in Qingdao Central Hospital were retrospectively analyzed. The general clinical information, MRI features, and 18F-FDG PET/CT features of patients were analyzed. χ2 test, Fisher exact test, and Mann-Whitney U test were used to analyze the data. The independent predictors of DCIS were analyzed by logistic regression analysis. The value of different indicators in diagnosing DCIS was analyzed using ROC curves analysis, and Delong test was used to assess the differences among AUCs. Results:The differences in tumor metabolic volume (MTV; 18.55(10.90, 76.30) vs 4.00(2.00, 11.45)cm 3) and total lesion glycolysis (TLG; 44.85(25.30, 125.30) vs 9.40(6.68, 22.35)g) of breast lesion, enhancement pattern (non-mass enhancement (NME); 8/12 vs 29.4%(10/34)), lobulation sign (0/12 vs 58.8%(20/34)), and apparent diffusion coefficient (ADC; 1.33 (1.16, 1.63)×10 -3vs 1.08 (0.75, 1.28)×10 -3mm 2/s) between DCIS and early stage IDC groups were statistically significant ( Z values: from -3.91 to -2.56, χ2=5.17, all P<0.05). When differentiating DCIS from early stage IDC, NME (odds ratio ( OR)=36.50, 95% CI: 2.15-618.52, P=0.013), ADC ( OR=7.85, 95% CI: 1.11-55.46, P=0.044), and TLG ( OR=1.06, 95% CI: 1.02-1.11, P=0.007) were independent predictors. The AUC of the three predictors combination was 0.941, which was higher than those of single predictors ( Z values: 2.00-2.80, P values: 0.005-0.046). Conclusion:The combination of 18F-FDG PET/CT and MRI improves the efficacy of differential diagnosis between DCIS and early stage IDC, thereby providing a basis for developing personalized treatment plans for patients.

Objective:To analyze the changes in the costs of hospital rehabilitation after the reform of health insurance payments in the past 6 years, and to identify relevant factors which can provide a reference for the reform of the health insurance payment system in rehabilitation department.Methods:Information on 16, 827 patients hospitalized in the rehabilitation department of The First Affiliated Hospital of Xi′an Jiaotong University between May 2018 and May 2024 was collected and subjected to non-parametric analysis.Results:The average hospitalization cost of rehabilitation department patients over the six years was Y14, 574.92±10, 524.79. During that time the proportion of the cost attributable to Western medicine decreased from 17.1% in 2018 to 7.6% in 2024. The proportion of the patients with hypertension was 51.94%, followed by diabetes mellitus (20.10%). Those with infections had the highest total hospitalization costs. Motor disorders were the most common dysfunction (59.02%), followed by speech disorders (17.45%). Patients with swallowing disorders had the highest hospitalization costs. After the payment system shifted from fee-for-service (FFS) to payment by diagnosis-related group (DRG) in 2023, the average daily inpatient expenditures for rehabilitation patients with all types of diseases gradually declined, reaching its lowest level in 2024.Conclusions:After the health insurance payments shifted from FFS to DRG, the proportion of in patients′ total drug costs decreased annually, and the average daily costs of patients with different types of diseases also decreased significantly, but the comprehensive service fee and diagnostic costs increased.

Objective:To explore the clinical features and genetic etiology of a child with a SETD1B gene variant causing seizures and language delay. Methods:A child with a SETD1B gene variant admitted to the Department of Pediatric Neurology at the Third Affiliated Hospital of Zhengzhou University in September 2022 was selected as the study subject. Clinical data of the child were collected, and peripheral blood samples from the child and her parents were obtained. Whole exome sequencing (WES) was performed for genetic testing, and Sanger sequencing was used for familial validation of the candidate variant. Using " SETD1B" and " epilepsy" as the Chinese and English keywords, relevant cases were retrieved from databases including CNKI, Wanfang Data, OMIM and PubMed, with the search period spanning from database inception to June 2024. Results:① The child was a 6-year-old female presenting with myoclonic seizures accompanied by global developmental delay. ② WES and Sanger sequencing revealed that the child has carried a de novo SETD1B gene variant, namely, c. 5582G>A (p.Cys1961Tyr). According to the American College of Medical Genetics and Genomics (ACMG) guidelines for sequence variant interpretation, this variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP2+ PP3). ③ The child was not controlled with effective doses of valproate, levetiracetam, or clonazepam but was successfully managed with low-dose lamotrigine. Follow-up electroencephalography showed normal results, and developmental progress gradually improved. ④ A total of 37 epilepsy cases with SETD1B gene variants were reported across six studies. The predominant seizure types included absence seizures and myoclonic absence seizures, accompanied by delayed language development. The response to pharmacological treatment was generally poor, with no statistically significant difference in incidence between males and females. Conclusion:SETD1B gene variant may induced neurological disorders with drug-resistant epilepsy and severe clinical manifestations. Lamotrigine is effective in controlling the epileptic seizures.

Biochemistry,as a fundamental course for science and engineering majors related to biology and chemistry,holds a significant position in the curriculum.The course team at Dalian Minzu University is committed to teaching innovation,adopting the outcome-based education(OBE)concept for teaching de-sign and incorporating ideological and political elements,in order to achieve the dual goals of knowledge transmission and value guidance.The team has established a three-dimensional teaching goal of"knowl-edge,morality,and ability",covering"consolidating core knowledge,cultivating moral sentiment,and enhancing innovation ability".Through a multi-dimensional integrated teaching method of"three integra-tions and five combinations",multiple rounds of teaching practice have been carried out in the applied chemistry major using"classification and specificity of enzyme"as an example.The output of teaching re-sults and survey questionnaires show that students highly recognize the teaching design and its"process-based learning"evaluation method,fully reflecting the student-centered teaching idea.Research has shown that OBE design combined with ideological and political elements can effectively promote students' knowl-edge acquisition,moral growth,and innovation ability improvement in the course of Biochemistry.This teaching design not only helps students construct correct worldviews,outlooks on life,and values,but also significantly enhances their innovative thinking and practical abilities.This teaching design can not only ef-fectively improve the teaching quality of the course,but also provide new perspectives and ideas for the teaching design of Biochemistry,realizing the organic integration of professional knowledge imparting and i-deological and political education,and has certain innovation and practical significance.

OBJECTIVES: To evaluate the application value of genetic newborn screening (gNBS) in the Yunnan region. METHODS: A prospective study was conducted with a random selection of 3 001 newborns born in the Yunnan region from February to December 2021. Traditional newborn screening (tNBS) was used to test biochemical indicators, and targeted next-generation sequencing was employed to screen 159 genes related to 156 diseases. Positive-screened newborns underwent validation and confirmation tests, and confirmed cases received standardized treatment and long-term follow-up. RESULTS: Among the 3 001 newborns, 166 (5.53%) were initially positive for genetic screening, and 1 435 (47.82%) were genetic carriers. The top ten genes with the highest variation frequency were GJB2 (21.29%), DUOX2 (7.27%), HBA (6.14%), GALC (3.63%), SLC12A3 (3.33%), HBB (3.03%), G6PD (2.94%), SLC25A13 (2.90%), PAH (2.73%), and UNC13D (2.68%). Among the initially positive newborns from tNBS and gNBS, 33 (1.10%) and 47 (1.57%) cases were confirmed, respectively. A total of 48 (1.60%) cases were confirmed using gNBS+tNBS. The receiver operating characteristic curve analysis demonstrated that the areas under the curve for tNBS, gNBS, and gNBS+tNBS in diagnosing diseases were 0.866, 0.982, and 0.968, respectively (P<0.05). DeLong's test showed that the area under the curve for gNBS and gNBS+tNBS was higher than that for tNBS (P<0.05). CONCLUSIONS gNBS can expand the range of disease detection, and its combined use with tNBS can significantly shorten diagnosis time, enabling early intervention and treatment.
Humans ; Infant, Newborn ; Neonatal Screening ; Genetic Testing ; Female ; Male ; Follow-Up Studies ; Prospective Studies ; China