ObjectiveTo explore the effects of the Tai Chi training on bone density， bone turnover markers， and heart rate variability for people with high-risk osteoporosis， and to provide evidence for the prevention of osteoporosis at early stage. MethodsSixty-six cases of people with high risk of osteoporosis were included， and they were divided into 33 cases each in the intervention group and the control group using the random number table method. The control group received osteoporosis health education three times a week， and the intervention group received Tai Chi training under the guidance of a trainer three times a week for 40 mins each time on the basis of the control group， and both groups were intervened for 12 weeks. Dual-energy X-ray absorptiometry was used to measure the bone density of L₁~L₄ vertebrae， bilateral femoral necks and bilateral total hips in the two groups before and after the intervention； enzyme-linked immunosorbent assay was used to determine bone turnover markers before and after the intervention， including pro-collagen type Ⅰ pro-amino-terminal prepropyl peptide （P1NP） and β-collagen type Ⅰ cross-linking carboxy-terminal peptide （β-CTX）. Seven cases with good compliance in the intervention group were selected. After wearing the heart rate sensor， they successively performed Tai Chi training and walking activities recommended by the guideline for 20 mins each， and the heart rate variability （HRV） during exercise was collected， including time-domain indexes such as standard deviation of normal sinus intervals （SDNN）， root-mean-square of the difference between adjacent RR intervals （RMSSD）， frequency-domain metrics such as low-frequency power （LF）， high-frequency power （HF）， and low-frequency/high-frequency power ratio （LF/HF）， as well as nonlinear metrics such as approximate entropy （ApEn）， sample entropy （SampEn）. ResultsFinally， 63 cases were included in the outcome analysis， including 30 cases in the intervention group and 33 cases in the control group. After the intervention， the differences of L₁~L₄ vertebrae， bone density of bilateral femoral neck and bilateral total hip in the intervention group were not statistically significant when compared with those before intervention （P＞0.05）， while the bone density of all parts of the control group decreased significantly compared with that before intervention （P＜0.05）， and the difference in the bone density of the L₁~L₄ vertebrae， bilateral femoral neck， and the right total hip before and after the intervention of the intervention group was smaller than that of the control group （P＜0.05）. The differences in P1NP and β-CTX between groups before and after intervention was not statistically significant （P＞0.05）. Compared with walking exercise， LF decreased， HF increased and LF/HF decreased during Tai Chi exercise （P＜0.05）； the time domain indexes and non-linear indexes between groups had no statistically significant difference （P＞0.05）. ConclusionTai Chi exercise can maintain lumbar， hip， and femoral bone density and improve sympathetic/parasympathetic balance in people at high risk for osteoporosis， but cannot significantly improve bone turnover markers.

Many triterpenoid compounds have been successfully heterologously synthesized in Saccharomyces cerevisiae. To increase the yield of triterpenoids, various metabolic engineering strategies have been developed. One commonly applied strategy is to enhance the supply of precursors, which has been widely used by researchers. Squalene, as a precursor to triterpenoid biosynthesis, plays a crucial role in the synthesis of these compounds. This study primarily investigates the effect of different squalene levels in chassis strains on the synthesis of triterpenoids(oleanolic acid and ursolic acid), and the underlying mechanisms are further explored using real-time quantitative PCR(qPCR) analysis. The results demonstrate that the chassis strain CB-9-5, which produces high levels of squalene, inhibits the synthesis of oleanolic acid and ursolic acid. In contrast, chassis strains with moderate to low squalene production, such as Y8-1 and CNPK, are more conducive to the synthesis of oleanolic acid and ursolic acid. The qPCR analysis reveals that the expression levels of ERG1, βAS, and CrCYP716A154 in the oleanolic acid-producing strain CB-OA are significantly lower than those in the control strains C-OA and Y-OA, suggesting that high squalene production in the chassis strains suppresses the transcription of certain genes, leading to a reduced yield of triterpenoids. Our findings indicate that when constructing S. cerevisiae strains for triterpenoid production, chassis strains with high squalene content may suppress the expression of certain genes, ultimately lowering their production, whereas chassis strains with moderate squalene levels are more favorable for triterpenoid biosynthesis.
Squalene/analysis* ; Saccharomyces cerevisiae/genetics* ; Triterpenes/metabolism* ; Metabolic Engineering ; Oleanolic Acid/biosynthesis* ; Ursolic Acid

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*

ObjectiveTo investigate the differences in clinical efficacy of different medication regimens of Wangbi Tablets （尪痹片） for knee osteoarthritis （KOA） in a real-world setting， providing a basis for rational clinical use of Wangbi Tablets. MethodsA prospective registry study was conducted， involving 2，999 KOA patients registered in 30 hospitals nationwide from January 26th， 2019， to December 17th， 2021. Based on the use of Wangbi Tablets during the observation period， patients were divided into a monotherapy group （1，507 cases） and a combination therapy group （1，492 cases）， and the combination group can be further divided into Wangbi Tablets plus Chinese medicine （CM）， Wangbi Tablets plus western medicine （WM）， and Wangbi Tablets plus Chinese and western medicine （CM+WM） subgroups. The baseline data of patients in the monotherapy group and the combination group were compared， including age， gender， body weight， medication time， clinical stage， K-L grade， and others. Efficacy indicators included the Visual Analog Scale （VAS） score， Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC） score， and EuroQol five-dimensional （EQ-5D） health index， which were evaluated before and after 4-， 8- and 12-week treatment， and the difference before and after treatment was calculated after 4， 8 and 12 weeks of treatment. The difference between the baseline and 12 weeks of treatment of all the above indicators was used as the dependent variables， and gender， age， body mass index （BMI）， course of disease， K-L grade， and clinical stage were used as independent variables， when multiple linear regression was taken to explore the influencing factors of the efficacy. At the same time， the occurrence of major symptoms （including morning stiffness， joint swelling， soreness of waist and knees， fear of wind， and fear of cold） was counted， and the disappearance of symptoms at each time point was counted after 4， 8， and 12 weeks of treatment. ResultsAt baseline， there were no statistically significant differences in gender and age distribution between the monotherapy and combination therapy groups （P＞0.05）； the proportion of patients in the acute stage and recovery stage was higher in the monotherapy group than in the combination therapy group， while the proportion in the remission stage was lower （P＜0.05）； the VAS score was higher in the monotherapy group， and the EQ-5D index was lower （P＜0.01）， with no statistically significant difference in total WOMAC score between the two groups （P＞0.05）. Compared to those measured before treatment and at previous timepoint， the VAS score and WOMAC total score significantly decreased in both groups， while EQ-5D value increased （P＜0.05）. The difference in VAS score between baseline and after 12-week treatment was higher in the monotherapy group than the combination group， while the differences in WOMAC total score and EQ-5D value between baseline and after 4-， 8- and 12-week treatment were higher in the combination group （P＜0.05）. Multiple linear regression showed that VAS score before treatment had greatest impact on pain improvement （P＜0.01）， and compared to Wangbi Tablets monotherapy， the combination of Wangbi tablets with WM or CM had larger associations with pain improvement （P＜0.05）； and Wangbi Tablets had better efficacy when the course of treatment was ＞28 days （P＜0.01）. Wangbi Tablets plus WM had a better effect on improving the overall function of the knee joint than Wangbi Tablets alone （P＜0.01）； and the efficacy of Wangbi Tablets with a course of treatment ＞28 days was better （P＜0.05）. The improvement of quality of life of patients in the attack and remission stages was more obvious than that in the recovery stage （P＜0.01）； Wangbi Tablets plus WM or CM had a better effect on improving quality of life than Wangbi Tablets alone （P＜0.05）. Before treatment， the proportion of patients with morning stiffness， soreness of waist and knees， fear of wind and chills in the monotherapy group was higher than that in the combination group （P＜0.01）. The proportion of main symptoms in both groups decreased after 4， 8 and 12 weeks of treatment （P＜0.05）. After 4 weeks of treatment， the disappearance rate of each main symptom in the combination group was higher than that in the monotherapy group， and after 12 weeks of treatment， the disappearance rate of fear of wind in the monotherapy group was higher than that in the combination group， while the disappearance rate of joint swelling and soreness of waist and knees was lower （P＜0.05）. ConclusionWangbi Tablets， whether used alone or in combination with other medications， is effective throughout the course of KOA， with greater benefits in improving joint function and quality of life during the acute and remission stages compared to the recovery stage. Combination therapy had a faster onset of effect， but began to converge with monotherapy after 8 weeks. The best efficacy was observed with the combination of Wangbi Tablets with WM， followed by combination with CM.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective:To investigate the alteration in iodine nutritional status and influence on thyroid function in the elderly aged≥65 years following water source modification in high iodine areas.Methods:Data from Yaoji Town, Xuzhou, Jiangsu(an area with high iodine due to water sources) of the national epidemiological survey on thyroid diseases, iodine nutrition, and diabetes(TIDE study) in 31 provinces and cities in China from 2015 to 2017 were utilized. Additionally, data from the screening, monitoring, and intervention on thyroid diseases(TOPS study) in the elderly(≥65 years) in Shunhe Town, Suqian, Jiangsu(an area with iodine levels exceeding the recommended amount), and Yaoji Town, Xuzhou from May to August 2021, are included. Each subject completed a questionnaire, physical examination, laboratory tests and thyroid ultrasound examinations. A total of 2 717 subjects aged≥65 years were included, including group 1, 258 subjects in TIDE study; Group 2, 1 313 subjects in TOPS Xuzhou area; Group 3, 1 146 subjects in TOPS Suqian area.Results:The urinary iodine concentration(UIC) in group 2 was significantly lower than that in group 1 [(235.16±67.09)μg/L vs (491.58±384.93)μg/L, P<0.001], but no significant difference compared with group 3 [(235.16±67.09) μg/L vs(231.62±66.11) μg/L, P>0.05]. The serum TSH level in group 2 was significantly lower than that in group 1 [(2.92±5.14)μIU/mL vs (4.15±9.19)μIU/mL, P<0.001]. Compared with group 2 and 3, the prevalence of subclinical hypothyroidism in the elderly in group 1 was the highest(22.48% vs 10.13% and 8.12%, P<0.001). TSH levels were linearly correlated with age in both excessive iodine and more than adequate iodine nutrition areas. TSH level was gradually increased with age. Conclusion:The alteration in TSH levels among the elderly is notably linked to both aging and iodine status. The prevalence of hypothyroidism in the elderly can be significantly reduced when the iodine nutrition status of the elderly returns to normal.

Gray matter heterotopia is a neurodevelopmental disorder characterized by abnormal distribution of gray matter in the brain cortex,and epilepsy is the most common clinical symptom of this disease.This article summarizes the etiology,pathogenesis,clinical manifestations,examination,and treatment of gray matter heterotopia and epilepsy,so as to improve the understanding of the disease.

Objective: Patients with schizophrenia are living at the border of society and their sexuality is often neglected. The aim of the study is to explore the association among The Brief Psychiatric Rating Scale (BPRS), quality of life (QoL), Taiwanese Depression Questionnaire, and Sexual Desire Inventory in people with schizophrenia (PwS). Methods: This study used a cross-sectional design with 277 psychiatric inpatients. A descriptive analysis, difference analysis, and logistic regression model were presented to identify relevant variables that may affect the probability of good QoL. Results: The study showed that male PwS had higher scores of standard deviation (SD) than females in PwS. The study also showed that smoking, early illness onset age, and shorter illness duration demonstrated a significantly higher SD. The logistic regression analysis showed that BPRS, depression, and SD significantly affected the probability of QoL. By structural equation model, SD would be positively correlated with mental status and SD would indirectly influence QoL. Conclusion Our results showed psychological and sociological factors interactions may contribute to the QoL and SD for PwS. This study also demonstrated a close relationship between SD, depression, and BPRS. These factors may predict the probability of good life quality for the PwS.

OBJECTIVE: To investigate the effect of phorbol-12-myristate-13-ace-tate (TPA) on the proliferation and apoptosis of acute promyelocytic leukemia cell line NB4 and its molecular mechanism. METHODS: The effect of different concentrations of TPA on the proliferation of NB4 cells at different time points was detected by CCK-8 assay. The morphological changes of NB4 cells were observed by Wright-Giemsa staining. The cell cycle and apoptosis of NB4 cells after TPA treatment were detected by flow cytometry. The mRNA expressions of NB4 cells after TPA treatment were analyzed by high-throughput microarray analysis and real-time quantitative PCR. Western blot was used to detect the protein expression of CDKN1A, CDKN1B, CCND1, MYC, Bax, Bcl-2, c-Caspase 3, c-Caspase 9, PIK3R6, AKT and p-AKT. RESULTS: Compared with the control group, TPA could inhibit the proliferation of NB4 cells, induce the cells to become mature granulocyte-monocyte differentiation, and also induce cell G₁ phase arrest and apoptosis. Differentially expressed mRNAs were significantly enriched in PI3K/AKT pathway. TPA treatment could increase the mRNA levels of CCND1, CCNA1, and CDKN1A, while decrease the mRNA level of MYC. It could also up-regulate the protein levels of CDKN1A, CDKN1B, CCND1, Bax, c-Caspase 3, c-Caspase 9, and PIK3R6, while down-regulate MYC, Bcl-2, and p-AKT in NB4 cells. CONCLUSION TPA induces NB4 cell cycle arrest in G₁ phase and promotes its apoptosis by regulating PIK3/AKT signaling pathway.
Humans ; Leukemia, Promyelocytic, Acute ; Caspase 3/metabolism* ; Caspase 9/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Cell Line, Tumor ; Cell Division ; Apoptosis ; RNA, Messenger ; Cell Proliferation