ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Cinnabar(HgS) was widely used in ancient times for medicinal purposes, religious rituals, and pigments. A group of bright red powdery clumps was excavated from Mawangdui Tomb No.3 of the Han Dynasty. Early studies considered the clumps as evidence of cinnabar's medicinal use during the Qin-Han period. This study employed a range of archaeometric techniques, including extended-depth-of-field stereo imaging, micro-CT, scanning electron microscopy-energy dispersive spectroscopy, Raman spectroscopy, and Fourier transform infrared spectrometry FTIR, to systematically analyze the material composition and structural characteristics of these remains. The results revealed that the cinnabar particles were granular, finely ground, and tightly bound to silk matrix, with no detectable excipients typically associated with medicinal formulations. Micro-CT imaging indicated a well-preserved textile structure, with clear signs of sedimentary accumulation and mechanical damage. Based on historical and archaeological studies, this study suggested that these remains were more likely degraded accumulations of cinnabar-colored silk textiles rather than medicinal cinnabar. By clarifying the diversity of ancient cinnabar applications and preservation states, this study provides new insights for the archaeological identification of mineral medicinal materials and contributes to the standardized study of Chinese medicinal materials and understanding of the historical use of cinnabar.
History, Ancient ; China ; Humans ; Medicine, Chinese Traditional/history* ; Archaeology ; Drugs, Chinese Herbal/history* ; Spectroscopy, Fourier Transform Infrared ; Spectrum Analysis, Raman ; Mercury Compounds

Smoking is a well-established risk factor for periodontitis, yet the precise mechanisms by which smoking contributes to periodontal disease remain poorly understood. Recent advances in spatial transcriptomics have enabled a deeper exploration of the periodontal tissue microenvironment at single-cell resolution, offering new opportunities to investigate these mechanisms. In this study, we utilized Visium HD single-cell spatial transcriptomics to profile gingival tissues from 12 individuals, including those with periodontitis, those with smoking-associated periodontitis, and healthy controls. Our analysis revealed that smoking disrupts the epithelial barrier integrity, induces fibroblast alterations, and dysregulates fibroblast-epithelial cell communication, thereby exacerbating periodontitis. The spatial analysis showed that endothelial cells and macrophages are in close proximity and interact, which further promotes the progression of smoking-induced periodontal disease. Importantly, we found that targeting the endothelial CXCL12 signalling pathway in smoking-associated periodontitis reduced the proinflammatory macrophage phenotype, alleviated epithelial inflammation, and reduced alveolar bone resorption. These findings provide novel insights into the pathogenesis of smoking-associated periodontitis and highlight the potential of targeting the endothelial-macrophage interaction as a therapeutic strategy. Furthermore, this study establishes an essential information resource for investigating the effects of smoking on periodontitis, providing a foundation for future research and therapeutic development for this prevalent and debilitating disease.
Humans ; Gingiva/cytology* ; Smoking/adverse effects* ; Male ; Periodontitis/pathology* ; Single-Cell Analysis ; Female ; Adult ; Middle Aged ; Macrophages ; Fibroblasts ; Endothelial Cells ; Case-Control Studies ; Chemokine CXCL12/metabolism*

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*

OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective To measure the transaction costs of compact urban medical groups and analyze the evaluation of transaction costs by various stakeholders.Methods Using the typical sampling method,it took the Compact Urban Medical Group of J District General Hospital in Zhengzhou City,Henan Province as an example.A questionnaire sur-vey was conducted on the construction party(health administration department,leading hospital and member units)and related staff from January 19 to 24,2024.The contents of the survey included institutional statements,basic information of the respondents,relevant fees or costs of each participant,and the evaluation of transaction costs by the staff of each institutional participant.Results In 2023,the total transaction cost of District J Medical Group in Zhengzhou City was 75 811 014.49 yuan;the majority of transaction costs were borne by the leading hospi-tal(98.1％);all stakeholders confirmed the existence of transaction costs in the medical group,but there were dif-ferences in the perception of the manifestations and distribution of transaction costs(P＜0.05).Conclusion The transaction costs of compact urban medical group are high,most of which are borne by the leading hospital;The stakeholders have not yet clearly understood the form and distribution of transaction costs.The measures to deal with transaction costs include"facing up to the widespread existence of transaction costs","improving the compensation incentive mechanism"and"establishing a saving system supply path".

Objective To measure the transaction costs of compact county medical alliance and propose counter-measures.Methods Based on Williamson-Zhang Wuchang analysis paradigm,it established the measure matrix of transaction cost of compact county medical alliance.Through the typical sampling method,the medical community of D city in Haixi Prefecture,Qinghai Province was selected as a research example to carry out an empirical study.Results The total transaction cost of the compact county medical community was 6 292 500.00 yuan,the transac-tion cost of the leading hospital was 6 234 300.00 yuan,accounting for 99.07％,and the special investment of the leading hospital reached to 5 887 100.00 yuan,accounting for 94.43％.The total transaction cost of the 298 referred patients was 308 400.00 yuan,and the average transaction cost per patient was 1 035.05 yuan.Conclusion The transaction costs of compact county medical alliance was generally high,most of which was borne by the leading hospital,and the patients also had to bear the corresponding transaction costs.In the next stage,the transaction costs should be dealt with from three aspects,including recognizing the secrecy and universality of the transaction costs,establishing economical system supply and establishing a sound compensation mechanism.

Objective To measure the transaction costs of the health management alliance with the clue of the re-ferral treatment of patients with hypertension and diabetes.Methods Based on the Williamson-Zhang Wuchang analy-sis paradigm,a transaction cost measurement matrix of health management alliance was established.Through the typical sampling method,the health management alliance of County N in Shandong Province was selected as a re-search example to carry out empirical research.Results In 2023,the total transaction costs of the sampled health management alliance reached to 6 726 700.00 yuan,and the average transaction cost per referral patient was 3 846 yuan.The leading hospital accounted for 79.45％of the transaction cost,followed by the CDC.Meanwhile,busi-ness coordination cost accounted for 47.18％of the total transaction cost,and the average transaction cost per refer patient with hypertension or diabetes was 700.90 yuan.Conclusion The total transaction costs of the health manage-ment alliance was large,and it was mainly borne by the leading hospital.Patients also need to bear considerable transaction costs.The countermeasures included improving the service integration mechanism,establishing economi-cal system supply path,and coordinating actions between social health insurance system and health care system.

OBJECTIVE To investigate the efficacy and safety of clobazam in the additional treatment of refractory epilepsy in children， and provide reference for clinically safe and rational drug use. METHODS The literatures about additional clobazam treatment for refractory epilepsy in children were searched from PubMed， The Cochrane Library， Embase， CNKI， VIP and Wanfang database during the inception to November 2023. After literature screening and data extraction， the quality of included literature was evaluated according to quality evaluation tool for methodological evaluation indicators of non-randomized controlled trial， and then meta-analysis of single-group rate and sensitivity analysis were performed by using RevMan 5.3 software. RESULTS Finally， 18 one-arm studies were included， with a total of 1 424 children. The results showed that compared with before additional treatment， the proportion of patients with seizures-free （proportion of patients with seizure reduction of 100%） was 24%[95%CI （0.18，0.32）， P＜0.000 01] after conversion； the proportion of patients with seizure reduction ≥75% was 32%[95%CI（0.25，0.40）， P＜0.000 1] after conversion； the proportion of patients with seizure reduction ≥50% was 53%[95%CI（0.44，0.61），P＜0.000 01]； the proportion of patients with seizure reduction ＜50% or no change was 35%[95%CI（0.24，0.49），P＝0.04] after conversion； the proportion of patients with seizure increase was 9%[95%CI（0.05，0.18），P＜0.000 01] after conversion. The proportion of patients with adverse reactions was 31%[95%CI（0.23，0.40），P＜0.000 1] after conversion； the proportion of patients with discontinuation due to adverse reactions was 10%[95%CI（0.07， 0.15）， P＜0.000 01] after conversion. The common adverse drug reactions were drowsiness， fatigue and behavior change， etc. The results of the sensitivity analysis showed that the study was robust. CONCLUSIONS Clobazam is an effective additional therapy for refractory epilepsy in children， but its adverse effects should be vigilant.