ObjectiveTo observe the analgesic efficacy and safety of Qihuang acupuncture theory combined with opioid analgesics in patients with moderate to severe cancer pain due to lung cancer. MethodsPatients with moderate to severe cancer pain from lung cancer were randomly divided into Qihuang acupuncture group and control group， with 33 cases in each group. The control group was treated with long-acting opioid analgesics at maintenance doses and supplementary analgesic medications as needed. In case of breakthrough pain， short-acting opioids were used for rescue. The Qihuang acupuncture group received Qihuang acupuncture treatment in addition to the treatment used in the control group， administered once every other day， with 3 sessions constituting one treatment course. The treatment duration for both groups was 5 days. The primary outcome was the change in pain intensity， measured using the numerical rating scale （NRS） before and after treatment， and the NRS change rate was calculated. Secondary endpoints included the daily NRS change rate， the Eastern Cooperative Oncology Group （ECOG） Performance Status （PS） score， the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire （EORTC QLQ-C30） score， and the 24-hour equivalent hydrocodone sustained-release tablet dose. Laboratory tests， including routine blood， urine， stool， liver function， and kidney function， were performed before and after treatment. Adverse events were recorded throughout the trial. ResultsAll patients completed the trial， and both groups showed a decrease in average NRS scores and PS scores after treatment， with the Qihuang acupuncture group showing lower average NRS scores and PS scores than the control group （P＜0.05 or P＜0.01）. After treatment， the NRS change rate in the Qihuang acupuncture group was （0.42±0.17）， significantly higher than that in the control group （0.14±0.27， P＜0.01）. The daily NRS change rate during treatment was also higher in the Qihuang acupuncture group compared to the control group （P＜0.01）. The Qihuang acupuncture group showed an increase in overall health status and functional scores in the EORTC QLQ-C30， and a decrease in symptom scores for fatigue， nausea and vomiting， pain， dyspnea， insomnia， appetite loss， constipation， and financial difficulties. In contrast， overall health status and constipation scores in the control group increased， while scores of fatigue， nausea and vomiting， pain， and appetite loss decreased （P＜0.05 or P＜0.01）. After treatment， the 24-hour equivalent hydrocodone sustained-release tablet dose did not show significant difference in the Qihuang acupuncture group （P＞0.05）， while the control group showed a significant increase in the 24-hour dose （P＜0.01）. No significant abnormalities were observed in laboratory tests before and after treatment in either group. During the study， the incidence of nausea and vomiting as well as constipation in the Qihuang acupuncture group was both 3.03% （1/33）， while the incidence in the control group was 27.27% （9/33） and 36.36% （12/33）， respectively， with the Qihuang acupuncture group showing significantly lower incidence （P＜0.01）. No serious adverse reactions were observed in either group. ConclusionQihuang acupuncture therapy combined with opioid analgesics is more effective than using opioids alone in relieving pain in patients with moderate to severe cancer pain due to lung cancer. It can improve the patients' physical condition and quality of life， reduce the dose of opioid analgesics， and has good safety.

Objective To investigate the effect of gentiopicroside on osteogenic differentiation of human bone marrow mesenchymal stem cells (BMSCs), and to determine whether its mechanism involves the stromal cell-derived factor 1(SDF-1)/C-X-C chemokine receptor 4 (CXCR4) pathway. Methods BMSCs were divided into six groups: normal culture control group, osteogenic induction model group, low-dose gentiopicroside (L-gentiopicroside, 10 μmol/L) group, medium-dose gentiopicroside (M-gentiopicroside, 20 μmol/L) group, high-dose gentiopicroside (H-gentiopicroside, 40 μmol/L) group, and H-gentiopicroside+SDF-1/CXCR4 pathway inhibitor (AMD3100) group (H-gentiopicroside+AMD3100, 40 μmol/L gentiopicroside+10 μg/mL AMD3100). Cell viability, apoptosis, ALP activity, mineralized nodule formation, and protein levels of the SDF-1/CXCR4 pathway were assessed using the CCK-8 assay, flow cytometry, ALP staining, Alizarin Red S staining, and Western blotting, respectively. Results No mineralized nodules were observed in either the control and model group, although the color of the model group deepened. Compared with the control group, the model group showed significantly increased A value, ALP activity, expression levels of Runt related transcription factor 2 (RUNX2), osteopontin (OPN), SDF-1, CXCR4 proteins, along with a lower apoptosis rate. Compared with the model group, the L-gentiopicroside, M-gentiopicroside and H-gentiopicroside groups showed dose-dependently (L Humans ; Receptors, CXCR4/genetics* ; Mesenchymal Stem Cells/metabolism* ; Chemokine CXCL12/genetics* ; Iridoid Glucosides/pharmacology* ; Osteogenesis/drug effects* ; Cell Differentiation/drug effects* ; Signal Transduction/drug effects* ; Cells, Cultured ; Apoptosis/drug effects* ; Bone Marrow Cells/metabolism*

OBJECTIVES: To explore the mechanism through which moxibustion promotes endometrial repair in rats with in thin endometrium (TE). METHODS: Female SD rats were randomized into control group, 95% anhydrous ethanol-induced TE model group and moxibustion (at "Guan Yuan") group. High-throughput sequencing was used to identify the target genes of TE, and the targeting relationship between miR-223-3p and NLRP3 was verified using a dual luciferase assay. Histopathological of rat uterus was observed with HE staining, and expressions of miR-223-3p and NLRP3 were detected using RT-qPCR; serum levels of IL-1β and IL-18 of the rats were detected using ELISA, and protein expressions of NLRP3, ASC, caspase-1 and GSDMD in the uterus were detected with Western blotting. The pregnancies of the rats after treatment were counted. RESULTS: Enrichment analysis of the differential genes suggested up-regulated inflammatory response in TE, and dual luciferase assay verified targeted inhibition of NLRP3 expression by miR-223-3p. The rat models of TE had significantly decreased endometrial thickness and reduced endometrial glands and blood vessels with enhanced mRNA expression of NLRP3, increased serum levels of IL-1β and IL-18, up-regulated protein expressions of NLRP3, ASC, caspase-1 and GSDMD, lowered pregnancy rates on both the affected and unaffected sides and the overall number of pregnancies. Treatment of the rat models with mo-xibustion obviously increased the endometrial thickness and the density of glands and blood vessels, up-regulated miR-223-3p expression, lowered serum IL-1β and IL-18 levels and the protein expressions of NLRP3, ASC, caspase-1 and GSDMD, and significantly increased the number of pregnancies. CONCLUSIONS Moxibustion at "Guan Yuan" acupoint up-regulates the expression of miR-223-3p, which results in targeted inhibition of NLRP3 to suppress pyroptosis and promote endometrial repair in rat models of TE.
Animals ; Female ; MicroRNAs/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Endometrium/pathology* ; Rats, Sprague-Dawley ; Rats ; Moxibustion ; Pyroptosis ; Up-Regulation ; Interleukin-1beta/metabolism* ; Interleukin-18 ; Caspase 1/metabolism*

Objective:To analyze regional differences in MMACHC gene variations among patients with cblC-type methylmalonic acidemia (MMA) in China and to explore the relationship between these variations and neonatal screening, biochemical markers and prognosis.Methods:Retrospective case summary. Clinical and laboratory data, including general condition, biochemical markers and genetic analysis, were collected from 1 859 cblC MMA patients from 2005 to 2023. Patients were divided into 7 groups according to their regions: north China, northeast China, east China, central China, south China, southwest China and northwest China. They were also classified into neonatal screening and non-neonatal screening groups. Mann-Whitney U and Kruskal-Wallis tests were used to compare biochemical marker levels. In contrast, the Chi-square test was applied to compare MMACHC gene variant frequencies, neonatal screening proportion, onset age and prognosis between groups. Results:Among 1 859 cases of cblC MMA, 1 019 were male and 840 were female, with a consultation age of 1.0 (0.1, 5.0) month. A total of 1 787 cases carried compound heterozygous or homozygous variants and only 1 variant site was identified in 72 cases. The 10 most frequent variants were c.609G>A (1 238 cases), c.658_660delAAG (343 cases), c.80A>G (284 cases), c.482G>A (239 cases), c.567dupT (191 cases), c.656_658delAGA (131 cases), c.217C>T (109 cases), c.394C>T (105 cases), c.445_446delTG (51 cases) and c.1A>G (50 cases). The frequency of the c.609G>A was the lowest in northwest China (28.8% (44/154), χ2=-18.42, P<0.05). The frequency of the c.567dupT was the most common in southwest China (25.0% (20/80), χ2=71.70, P<0.001) and c.656_658delAGA had the highest frequency in northeast China (9.3% (19/205), χ2=32.08, P<0.001). Non-missense variants (91.2% (62/68), 88.5% (46/52)) and early-onset patients (90.0% (36/40), 94.4% (34/36)) were both more prevalent in southwest and south China ( χ2=14.95, 31.69, both P<0.05). The proportion of neonatal screening was the lowest in south China (22.2% (8/36), χ2=98.48, P<0.05), where the mortality rate was the highest (19.1% (4/21), χ2=38.98, P<0.001). East China exhibited the highest frequency of missense variants (21.5% (339/1 579)), the highest proportion of patients identified through neonatal screening (54.5% (465/853)), and a more significant proportion of patients with good prognosis (36.6% (227/621), χ2=14.57, 93.49, 38.98, all P<0.05). In addition, the c.482G>A variant was more frequent in patients diagnosed by neonatal screening compared to those diagnosed by other methods (8.3% (132/1 586) vs. 5.9% (122/2 060), χ2=7.97, P<0.05). Conclusions:The frequency of MMACHC gene variation varies across different regions. The c.609G>A was least frequent in northwest China, c.567dupT was most common in southwest China, and c.656_658delAGA was most prevalent in northeast China. South China had the lowest neonatal screening rate and the highest mortality. At the same time, east China exhibited the highest frequency of missense variants, the highest proportion of patients identified through neonatal screening and the best prognosis. The c.482G>A variant was more frequent in patients diagnosed by neonatal screening compared to those diagnosed by other methods.

Background::Evidence indicates that low muscle strength is associated with an increased cardiovascular diseases (CVDs) risk. However, the association between muscle strength changes based on repeated measurements and CVD incidence remains unclear.Methods::The study used data from the China Health and Retirement Longitudinal Study in 2011 (Wave 1), 2013 (Wave 2), 2015 (Wave 3), and 2018 (Wave 4). Low muscle strength was defined as handgrip strength <28 kg for men or <18 kg for women, or chair-rising time ≥12 s. Based on changes in muscle strength from Waves 1 to 2, participants were categorized into four groups of Normal-Normal, Low-Normal, Normal-Low, and Low-Low. CVD events, including heart disease and stroke, were recorded using a self-reported questionnaire during Waves 3 and 4 visits. Cox proportional hazards models were used to investigate the association between muscle strength changes and CVD incidence after multivariable adjustments. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated with the Normal-Normal group as the reference.Results::A total of 1164 CVD cases were identified among 6608 participants. Compared to participants with sustained normal muscle strength, the CVD risks increased progressively across groups of the Low-Normal (HR = 1.20, 95% CI: 1.01-1.43), the Normal-Low (HR = 1.35, 95% CI: 1.14-1.60), and the Low-Low (HR = 1.76, 95% CI: 1.49-2.07). Similar patterns were observed for the significant associations between muscle strength status and the incidence risks of heart disease and stroke. Subgroup analyses showed that the significant associations between CVD and muscle strength changes were consistent across age, sex, and body mass index (BMI) categories.Conclusions::The study found that muscle strength changes were associated with CVD risk. This suggests that continuous tracking of muscle status may be helpful in screening cardiovascular risk.

ObjectiveTo investigate the current status and development needs of evidence-based medicine （EBM） capability in ethnic minority medicine， and explore effective strategies to enhance EBM capability in this field. MethodsThe questionnaire survey was conducted in various ethnic minority medical institutions and research organisations. The questionnaire covered three dimensions， firstly， perceptions and attitudes towards evidence-based medicine； secondly， advantages and challenges in the development of ethnic minority medicine； thirdly， demands and recommendations for enhancing evidence-based medicine capability in ethnic minority medicine. ResultsA total of 501 valid questionnaires were collected， of which 103 questionnaires were collected by re-sending to minority medicine regions with insufficient participation. The questionnaires included 354 responses （70.66%） from practitioners of minority medicine， including Tibetan medicine， Mongolian medicine， Uyghur medicine， Zhuang medicine， and Korean medicine. Among the 501 questionnaires， 146 respondents （29.14%） indicated that they knew about EBM， 355 respondents （70.86%） had either a "general understanding" or had "not heard about" EBM before， and 469 respondents （93.61%） believed that introducing ECM could promote the development of ethnic minority medicine. The primary challenge in promoting EBM in the field of ethnic minority medicine is the lack of professionals in EBM and a lack of understanding of how to apply it into clinical practice （442 respondents， 88.22%）. In the 9-point importance rating for enhancing evidence-based abilities， high scores were achieved in standardization of clinical practice guidelines （7.50±1.90） and methods for sample sizes in clinical research （7.45±1.90）. Regarding the demand for improving clinical research literacy， expert academic lectures， and experience sharing （404 respondents， 80.64%） and evidence-based methodology monographs on ethnic minority medicine （401 respondents， 80.04%） were emphasized. ConclusionsPractitioners in ethnic minority medicine hold a positive attitude towards integrating EBM. However， there remains substantial room for the education and dissemination of EBM. Enhancing evidence-based capabilities can be achieved through specific measures such as cultivating or recruiting talents in EBM， establishing evidence-based support platforms for clinical research， organizing regular academic lectures and exchanges， and strengthening the construction of theoretical frameworks and evaluation systems tailored to ethnic minority medicine， thereby following a path of evidence-based practices aligned with the unique characteristics of ethnic minority medicine.

The microcosmic syndrome differentiation is expounded from the the trinity life view of the body， qi， and spirit. This article analysed the relationship between micro-indicators and body， qi and spirit， considering that the abnormalities of micro-indicators in pathological states involve three different levels in terms of body， qi and spirit， and may reflect the degree of malfunction of body， qi and spirit and the dynamic changes of the focus during different pathological processes.Accordingly， based on the syndrome differentiation and treatment of traditional Chinese medicine， it is proposed that the macroscopic and the microscopic， the local and the whole， as well as the imbalance of body， qi and spirit reflected by microscopic and macroscopic indicators at different stages of disease should be combined to determine the corresponding treatment， thereby restoring the “harmony of body and spirit” of the human body.

Objective:To investigate the characteristics of 18F-FDG and 18F-9-fluoropropyl-(+ )-dihydrotetrabenazine (FP-(+ )-DTBZ; short for DTBZ) brain vesicular monoamine transporter type 2 (VMAT2) PET/CT imaging and analyze its clinical diagnostic value in Parkinson′s disease (PD) patients with or without rapid eye movement sleep behaviour disorder (RBD). Methods:From July 2022 to June 2023, 50 patients clinically confirmed with primary PD who underwent 18F-FDG and 18F-DTBZ PET/CT imaging in the First Affiliated Hospital of Zhengzhou University were prospectively collected. Among them, 18 patients with PD accompanied by RBD (PD-RBD(+ ) group; 16 males, 2 females, age (59.2±9.3) years); 32 patients without RBD (PD-RBD(-) group; 16 males, 16 females, age (57.7±10.2) years). Moreover, 10 healthy controls matched with the age of PD patients were included (5 males, 5 females, age (60.3±9.6) years). 18F-DTBZ specific uptake ratio (SUR) of bilateral striatum, caudate nucleus, anterior putamen, posterior putamen, nucleus accumbens, substantia nigra and other brain regions were obtained with occipital cortex as the reference region. Striatal anterior-posterior gradient and other related semi-quantitative indicators were calculated according to the corresponding formula. One-way analysis of variance (the least significant difference (LSD)- t test), Kruskal-Wallis rank sum test (Bonferroni correction), independent-sample t test and Mann-Whitney U test were used to analyze the data. Pearson correlation and Spearman rank correlation analyses were used to evaluate the correlations. ROC curve analysis was also performed. The differences in global glucose metabolism in two groups were compared using statistical parametric mapping (SPM). Results:PD-RBD(+ ) group had a significantly lower Mini-Mental State Examination (MMSE) or PD Sleep Scale (PDSS) score than PD-RBD(-) group ( z values: -3.12, -3.08, both P<0.01), and its contralateral striatal anterior-posterior gradient of the predominantly affected limbs was significantly lower than that in PD-RBD(-) group ( t=-2.73, P=0.009). SPM analysis showed that the glucose metabolism in the contralateral prefrontal lobe was higher than that in the PD-RBD (-) group ( t values: 3.11-3.57, all P<0.001). 18F-DTBZ SUR in the bilateral striatum, caudate nucleus, anterior putamen, posterior putamen, nucleus accumbens, substantia nigra were considerably lower in both groups compared to the healthy control group ( F values: 6.24-147.61, H values: 8.66-24.43, all P<0.05; post-hoc: LSD- t test, Bonferroni correction, all P<0.01). In the PD-RBD(-) group, contralateral striatal anterior-posterior gradient were negatively correlated with unified PD Rating Scale (UPDRS) score and modified Hoehn-Yahr (mH-Y) stage ( r=-0.35, P=0.048; rs=-0.39, P=0.026). The AUC for distinguishing PD-RBD(+ ) and PD-RBD(-) with a contralateral striatal anterior-posterior gradient was 0.706 (95% CI: 0.562-0.851, P=0.016), with the sensitivity and specificity of 59.4%(19/32) and 16/18, respectively. Conclusions:The decrease of contralateral striatal anterior-posterior gradient of VMAT2 is more obvious in patients with PD-RBD(+ ), and there are differences in brain metabolism between the two groups, suggesting that there may be different neuropathological changes and different pathophysiological mechanisms between PD patients with and without RBD. 18F-DTDZ PET/CT can provide imaging basis for the differential diagnosis of the disease subtypes.

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female ; Humans ; Uterine Cervical Neoplasms/drug therapy* ; Prospective Studies ; Quality of Life ; Neoplasm Staging ; Chemoradiotherapy ; Chemotherapy, Adjuvant/adverse effects* ; Adjuvants, Immunologic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies

Background Perfluoroalkyl substances (PFASs) are classified as persistent organic pollutants and have been widely detected in human. Studies investigating the associations between PFASs exposure and estimated glomerular filtration rate (eGFR) yielded inconsistent results, and little is known about the effects of PFASs on eGFR in population without kidney disease. Objective To explore the associations of exposure to PFASs with eGFR and renal dysfunction in population without kidney disease. Methods A total of 609 participants with an eGFR > 60 mL·min⁻¹·1.73 m⁻² and without renal impairment matched for sex and age (1∶1) were recruited from endocrinology department and medical examination center of two hospitals in Tianjin, China, from April 2021 to March 2022. Each subject was interviewed using a structured questionnaire to collect information about sex, age, height, weight, disease history, smoking, alcohol intake, etc. Clinical parameters were obtained from medical record, such as fasting blood glucose (FBG), creatinine (Cre), total cholesterol (TC), and triglyceride (TG). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by professionals using standard methods. The serum concentrations of PFASs were determined by liquid chromatography/mass spectrometry. Multivariable linear and logistic regression models were performed to evaluate the associations of PFASs exposure with eGFR and renal dysfunction, respectively. Subgroup analyses stratified by age and sex were also performed to assess the modified effects of covariates on the associations of PFASs exposure with eGFR. Results There were 283 males, accounting for 46.5% of the total population. The mean age of the participants was (56.86±12.47) years, and the average body mass index (BMI) was (25.59±3.84) kg·m⁻². Perfluoro-n-octanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluoro-n-nonanoic acid (PFNA), perfluoro-n-decanoic acid (PFDA), perfluoro-n-undecanoic acid (PFUnDA), sodium 1H, 1H, 2H, 2H-perfluoro-1-octanesulfonate (6:2 FTS), and perfluoropentane sulfonic acid (PFPeS) were positive in more than 75% of serum samples, and the corresponding median concentrations were 9.50, 1.67, 17.22, 1.86, 1.41, 0.78, 0.42, and 0.43 μg·L⁻¹, respectively. After full adjustments of sex, age, BMI, hypertension, diabetes, TC, TG, smoking, and drinking, the linear regression models showed that log₂-transformed PFHxS concentration was negatively associated with eGFR (b=−1.160, 95%CI: −2.280, −0.410). Compared with the lowest exposure tertile, the estimated change of eGFR in the highest tertile for PFHxS was significantly decreased (b=−2.471, 95%CI: −4.574, −0.368). Furthermore, compared with males, the negative association of PFHxS with eGFR was strengthened among females (female: b=−1.281, 95%CI: −2.388, −0.174; male: b=−0.781, 95%CI: −2.823, 1.261, P_interaction=0.043). Conclusion A significant negative association between serum PFHxS and eGFR is observed in the sampled population without kidney disease, and females are more susceptible to PFASs exposure than the males.