OBJECTIVE: Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA. METHODS: Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment. RESULTS: Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex. CONCLUSION EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects. Please cite this article as: Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 2025; 23(2): 159-168.
Animals ; Electroacupuncture ; Male ; Magnetic Resonance Imaging ; Depression/diagnostic imaging* ; Mice, Inbred C57BL ; Brain/diagnostic imaging* ; Disease Models, Animal ; Mice ; Pain/diagnostic imaging* ; Acupuncture Points

BACKGROUND: The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular disease in previous studies. However, it is unclear whether elderly people with long-term high AIP levels are more likely to develop coronary heart disease (CHD). Therefore, the aim of this study was to investigate the relationship between AIP trajectory and CHD incidence in elderly people. METHODS: 19,194 participants aged ≥ 60 years who had three AIP measurements between 2018 and 2020 were included in this study. AIP was defined as log₁₀ (triglyceride/high-density lipoprotein cholesterol). The group-based trajectory model was used to identify different trajectory patterns of AIP from 2018 to 2020. Cox proportional hazards models were used to estimate the hazard ratio (HR) with 95% CI of CHD events between different trajectory groups from 2020 to 2023. RESULTS: Three different trajectory patterns were identified through group-based trajectory model: the low-level group (n = 7410, mean AIP: -0.25 to -0.17), the medium-level group (n = 9981, mean AIP: 0.02-0.08), and the high-level group (n = 1803, mean AIP: 0.38-0.42). During a mean follow-up of 2.65 years, a total of 1391 participants developed CHD. After adjusting for potential confounders, compared with the participants in the low-level group, the HR with 95% CI of the medium-level group and the high-level group were estimated to be 1.24 (1.10-1.40) and 1.43 (1.19-1.73), respectively. These findings remained consistent in subgroup analyses and sensitivity analyses. CONCLUSIONS There was a significant correlation between persistent high AIP level and increased CHD risk in the elderly. This suggests that monitoring the long-term changes in AIP is helpful to identify individuals at high CHD risk in elderly people.

AIM To study the chemical constituents from the petroleum ether fraction of the roots of Gypsophila licentiana Hand.-Mazz.METHODS Silica gel,Sephadex LH-20 and semi-preparative HPLC were used for isolation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Eighteen compounds were isolated and identified as dibutyl phthalate(1),glyceryl arachidate(2),bis(2-ethylhexyl)terephthalate(3),9,12-octadecadienoic acid(Z,Z)-methyl ester(4),(3'S,4'S)-3'-acetoxy-4'-angeloyloxy-3',4'-dihydroseselin(5),3-(4-hydroxy-3-methoxyphenyl)-propanoic acid(6),bis(2-ethylhexyl)phthalate(7),2,2'-oxybis(1,4)-di-tert-butylbenzene(8),gypsogenin(9),3-keto,16α-hydroxy,24-noroleanolic acid(10),3-oxo-olean-12-en-28-oic acid(11),10-eicosenoic acid(12),hexacosanic acid(13),enniatin B(14),(R,Z)-21-methyl-8-pentatriacontene(15),ethyl gallate(16),stellarine A(17),pentacosane(18).CONCLUSION All compounds are isolated from this plant for the first time.

Objective To explore the predictive value of growth differentiation factor 15(GDF-15)for atrial fibrillation(AF)in patients with coronary heart disease(CHD).Methods A prospective observation cohort of 1261 elderly CHD patients was randomly sampled from the First Medical Center of Chinese PLA General Hospital from January 2012 to December 2015.ELISA was used to detect GDF-15 level in all the subjects,and their baseline data were collected.Until March 2023,93 patients were lost during the follow-up period,and finally 1168 patients completed the follow-up,with a median time of 9.4 years.According to AF occurred or not during the period,the eligible patients were divided into an AF group(197 cases)and a non-AF group(971 cases),and based on their medical history,also assigned into a stable angina pectoris(SAP,n=304)and an acute coronary syndrome group(ACS,n=864).Logistic regression analysis was used to determine whether GDF-15 is a risk factor for AF in elderly CHD patients.ROC curve was plotted to assess the predictive value of GDF-15,guideline recommended CHARGE-AF scoring model,and their combination for AF events in the patients.Results The AF group had significantly advanced age,larger proportions of smoking history,type 2 diabetes,hypertension,old myocardial infarction,stroke,ACS and administration of statins,higher ratio of angiotensin converting enzyme inhibi-tor/angiotensin receptor blocker,and elevated levels of GDF-15 and N-terminal pro-B-type natri-uretic peptide,and lower left ventricular ejection fraction,SAP incidence,and low-density lipopro-tein cholesterol,total cholesterol and triglycerides levels when compared with the non-AF group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that GDF-15 was not a risk factor for AF in elderly CHD patients(OR=0.92,95％CI:0.74-1.16,P=0.489),but was a risk factor for AF in SAP patients(OR=1.38,95％CI:1.07-2.79,P=0.015),and in ACS patients,still not a risk factor for AF(OR=0.81,95％CI:0.63-1.05,P=0.814).ROC curve analysis showed that the AUC value of GDF-15 combined with the CHARGE-AF scoring model in predic-ting AF was 0.682 in the elderly CHD patients,0.746 in the SAP patients,and 0.680 in the ACS patients.Conclusion Elevated GDF-15 level is an independent risk factor and predictor of AF in elderly SAP patients.In SAP patients,the combination of GDF-15 and CHARGE-AF scoring model further improves the predictive performance of AF occurrence.

AIM To study the chemical constituents from the petroleum ether fraction of the roots of Gypsophila licentiana Hand.-Mazz.METHODS Silica gel,Sephadex LH-20 and semi-preparative HPLC were used for isolation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Eighteen compounds were isolated and identified as dibutyl phthalate(1),glyceryl arachidate(2),bis(2-ethylhexyl)terephthalate(3),9,12-octadecadienoic acid(Z,Z)-methyl ester(4),(3'S,4'S)-3'-acetoxy-4'-angeloyloxy-3',4'-dihydroseselin(5),3-(4-hydroxy-3-methoxyphenyl)-propanoic acid(6),bis(2-ethylhexyl)phthalate(7),2,2'-oxybis(1,4)-di-tert-butylbenzene(8),gypsogenin(9),3-keto,16α-hydroxy,24-noroleanolic acid(10),3-oxo-olean-12-en-28-oic acid(11),10-eicosenoic acid(12),hexacosanic acid(13),enniatin B(14),(R,Z)-21-methyl-8-pentatriacontene(15),ethyl gallate(16),stellarine A(17),pentacosane(18).CONCLUSION All compounds are isolated from this plant for the first time.

Objective To explore the predictive value of growth differentiation factor 15(GDF-15)for atrial fibrillation(AF)in patients with coronary heart disease(CHD).Methods A prospective observation cohort of 1261 elderly CHD patients was randomly sampled from the First Medical Center of Chinese PLA General Hospital from January 2012 to December 2015.ELISA was used to detect GDF-15 level in all the subjects,and their baseline data were collected.Until March 2023,93 patients were lost during the follow-up period,and finally 1168 patients completed the follow-up,with a median time of 9.4 years.According to AF occurred or not during the period,the eligible patients were divided into an AF group(197 cases)and a non-AF group(971 cases),and based on their medical history,also assigned into a stable angina pectoris(SAP,n=304)and an acute coronary syndrome group(ACS,n=864).Logistic regression analysis was used to determine whether GDF-15 is a risk factor for AF in elderly CHD patients.ROC curve was plotted to assess the predictive value of GDF-15,guideline recommended CHARGE-AF scoring model,and their combination for AF events in the patients.Results The AF group had significantly advanced age,larger proportions of smoking history,type 2 diabetes,hypertension,old myocardial infarction,stroke,ACS and administration of statins,higher ratio of angiotensin converting enzyme inhibi-tor/angiotensin receptor blocker,and elevated levels of GDF-15 and N-terminal pro-B-type natri-uretic peptide,and lower left ventricular ejection fraction,SAP incidence,and low-density lipopro-tein cholesterol,total cholesterol and triglycerides levels when compared with the non-AF group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that GDF-15 was not a risk factor for AF in elderly CHD patients(OR=0.92,95％CI:0.74-1.16,P=0.489),but was a risk factor for AF in SAP patients(OR=1.38,95％CI:1.07-2.79,P=0.015),and in ACS patients,still not a risk factor for AF(OR=0.81,95％CI:0.63-1.05,P=0.814).ROC curve analysis showed that the AUC value of GDF-15 combined with the CHARGE-AF scoring model in predic-ting AF was 0.682 in the elderly CHD patients,0.746 in the SAP patients,and 0.680 in the ACS patients.Conclusion Elevated GDF-15 level is an independent risk factor and predictor of AF in elderly SAP patients.In SAP patients,the combination of GDF-15 and CHARGE-AF scoring model further improves the predictive performance of AF occurrence.

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

Objective To evaluate the pharmacokinetics(PK)of tenofovir alafenamide Fumarate tablets(25 mg)in healthy Chinese subjects after single oral administration to provide a basis for bioequivalence evaluation.Methods Using a single-dose,randomized,open-lable,two-period,two-way crossover design under fasting condition,while three-way crossover design under fed condition,42 healthy subjects respectively for fasting and fed study were enrolled,and randomized into two groups to receive a single dose of test product(T)or reference product(R)25 mg.Plasma concentration of tenofovir alafenamide and tenofovir were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.The pharmacokinetic parameters were calculated by WinNonlin software(8.1 version)using non-compartmental model,and bioequivalence evaluation was performed for the two preparations.Relevant safety evaluations were performed during the trial.Results The test product and the reference product under fasting study,the main PK parameters of tenofovir alafenamide were as follows:Cmax were(215.17±94.24)and(199.30±71.11)ng·mL-1;AUC0-t were(135.44±71.60)and(123.91±53.82)h·ng·mL-1;the main PK parameters of tenofovir were as follows:Cmax were(7.30±2.27)and(7.12±1.74)ng·mL-1,AUC0-t of tenofovir were(237.16±47.09)and(230.06±43.41)h·ng·mL-1,respectively.The test product and the reference product under fed study,the main PK parameters of tenofovir were as follows:Cmax were(197.69±82.19)and(197.10±110.54)ng·mL-1;AUC0-t were(197.69±82.19)and(197.10±110.54)h·ng·mL-1;the main PK parameters of tenofovir were as follows:CMax were(2.57±1.37)and(2.58±1.31)ng·mL-1;AUC0-t were(227.08±74.33)and(238.51±128.30)h·ng·mL-1,respectively.The 90％confidence interval for geometric mean ratio of Cmax,AUC0-tof T and R under fed condition were between 80.00％-125.00％,respectively.The incidence of adverse events in fasting and fed tests was 21.43％and 30.95％,respectively,and no serious adverse event was reported.Conclusion The test formulation and reference formulation of tenofovir alafenamide fumarate tablets were equivalent and was safe.

Objective To evaluate the feasibility of emergency percutaneous coronary intervention(PCI)with extracorporeal membrane oxygenation(ECMO)support in critically ill patients with acute myocardial infarction(AMI)and cardiogenic shock(CS).Methods Retrospective analysis of clinical data of AMI combined with CS patients admitted to the department of emergency of the Second Hospital of Hebei Medical University from December 2018 to December 2021,including gender,age,body mass index(BMI),past history(smoking,coronary heart disease,arrhythmia,diabetes,hypertension,hyperlipidemia,cerebrovascular disease);acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)score,highest vasoactive-inotropic score(VIS)within 24 hours of admission,the worst auxiliary examination values within 24 hours after admission:blood lactic acid(Lac),arterial partial pressure of oxygen(PaO2),cardiac troponin I(cTnI),alanine aminotransferase(ALT),total bilirubin(TBil),creatinine(Cr),serum potassium,left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF)],presence of malignant arrhythmia or cardiac arrest during emergency PCI,completion of PCI,and the 30-day prognosis,etc.Patients were divided into an ECMO group and a non-ECMO group based on whether ECMO was applied,to analyze differences in the above indicators between the two groups.Results There were no statistically significant differences between the ECMO group and the non-ECMO group in terms of gender,age,BMI,past history,APACHEⅡ,VIS and the worst auxiliary examination value within 24 hours after admission.The incidence of malignant arrhythmia or cardiac arrest events and 30-day mortality rate during emergency PCI in the ECMO group were significantly lower than those in the non-ECMO group[the incidence of malignant arrhythmia or cardiac arrest during emergency PCI was 17.9％(7/39)vs.45.0％(9/20),and the 30-day mortality was 46.2％(18/39)vs.75.0％(15/20),both P<0.05].The completion rate of PCI in the ECMO group was significantly higher than that in the non-ECMO group[100.0％(39/39)vs.80.0％(16/20),P<0.05].Conclusions For critically ill patients with AMI combined with CS,ECMO support can reduce the risk of malignant arrhythmia or cardiac arrest during emergency PCI,increase the completion rate of PCI,and reduce the 30-day mortality.With the support of the ECMO team,ECMO support emergency PCI is feasible.

Sucrose synthase plays a crucial role in the plant sugar metabolism pathway by catalyzing the production of uridine diphosphate (UDP)-glucose, which serves as a bioactive glycosyl donor for various metabolic processes. In this study, a sucrose synthase gene named CtSus was cloned from Cistanche tubulosa, a traditional Chinese medicine known for its rich content of diverse glycosides, based on transcriptome analysis results. The open reading frame of CtSus was 2 418 bp long encoding 805 amino acids. Sequence analysis revealed conserved domains associated with the plant sucrose synthase family at both the N-terminal and C-terminal regions of CtSus protein. Phylogenetic analysis demonstrated that CtSus shares a close evolutionary relationship with sucrose synthases from other plants within the same order. Functional identification of CtSus was performed through whole-cell catalysis coupling with UGT71BD1, a characterized glycosyltransferase enzyme. The results showed that the introduction of CtSus significantly enhanced the conversion rate of glycosylation catalyzed by UGT71BD1. The soluble expression of CtSus in Escherichia coli was further achieved using the pCold^TM TF expression vector. In vitro enzymatic assay indicated the activity of CtSus to catalyze the formation of UDP-glucose in the presence of sucrose and UDP. Real-time quantitative-polymerase chain reaction results showed that the expression patterns of CtSus gene in different parts of C. tubulosa and the suspension cell cultures of C. tubulosa under drought stress correlated with the accumulation patterns observed for phenylethanol glycosides, respectively. Furthermore, key amino acids and their interactions between enzyme and substrate were explored based on protein structure prediction and molecular docking results. Overall, our findings identify a sucrose synthase CtSus responsible for the supply of the active glycosyl donor UDP-glucose during the biosynthesis of glycoside products in C. tubulosa and have also provided a gene element that can be utilized in engineering strain construction for glycoside products production.