The clinical antiprotozoal drug nitazoxanide has been demonstrated to improve the experimental diabetes mellitus, lipid metabolism disorders, atherosclerosis and inhibit inflammation. Since the pathogenesis of heart failure with preserved ejection (HFpEF) is multifactorial and closely associated with the aforementioned diseases, we aim to study the effect of nitazoxanide on high-fat diet (HFD) plus L-NAME (N ω-nitro-l-arginine methyl ester)-induced HFpEF and metabolic syndrome in mice. We found that oral nitazoxanide improved cardiac hypertrophy, cardiac fibrosis, cardiac diastolic dysfunction, increased blood pressure, impaired exercise tolerance, impaired glucose handling, serum lipid disorders, hepatic steatosis, increased weight of white adipose tissues and kidney fibrosis in HFD + L-NAME-treated mice. In the established HFD + L-NAME-induced HFpEF and metabolic syndrome mouse model, therapeutic treatment with nitazoxanide rescued HFD + L-NAME-induced pathological phenotypes as mentioned above. The in vitro experiments revealed that tizoxanide, the active metabolite of nitazoxanide, increased the basal mitochondria metabolism of cardiomyocytes, inhibited cardiomyocyte hypertrophy and collagen secretion from cardiac fibroblasts, and relaxed phenylephrine- and U46619-induced constriction of rat mesenteric arteries, indicating that the direct effect of tizoxanide might partly contribute to the protective effect of nitazoxanide against HFpEF in vivo. The present study suggests that nitazoxanide might be a potential drug for HFpEF and metabolic syndrome therapy.

Drug addiction, a disorder characterized by chronic relapse and compulsive drug use, poses a significant threat to public safety and human health. Addictive substances can be categorized as natural, semi-synthetic, or synthetic based on their origin. Additionally, they can be classified into three groups according to their pharmacological targets: opioids, hallucinogens, and cannabinoids that act on G-protein-coupled receptors (GPCRs); alcohols, nicotine, ketamine, barbiturates, and benzodiazepines (BDZs) that affect ligand-gated ion channel-type receptors; and psychostimulants that interact with monoamine transporters. Current treatments for drug addiction primarily include substitution therapy and non-pharmacological approaches. However, these methods have limitations, particularly in addressing the underlying causes of relapse. Several drugs in clinical trials have demonstrated potential therapeutic effects for addiction to opioids, heroin, cocaine, and other substances. This review examines the origins and pharmacological mechanisms of addiction to naturally-derived psychoactive substances (NPS) and provides an overview of recent advancements in pharmacotherapy for drug addiction.
Humans ; Substance-Related Disorders/drug therapy* ; Psychotropic Drugs/therapeutic use* ; Animals

Objective To investigate the effect and mechanism of Xuanfu Daizhe Decoction on the proliferation,migration,and invasion activities of esophageal cancer cells.Methods Human e-sophageal cancer cell line EC 109 was treated with Xuanfu Daizhe Decoction at different concentrations,and the cells were divided into high-concentration group(200 μg/mL),medium-concentration group(100 μg/mL),low-concentration group(50 μg/mL),and blank group(0 μg/mL)based on the concentration.CCK-8 assay,wound healing assay,and Transwell invasion assay were used to detect the proliferation,migration,and invasion activities of the cells in each group,respectively.Western blot and cellular immunofluorescence staining were employed to detect the protein expression levels of glycolysis-related enzymes[hexokinase 2(HK2),lactate dehydrogenase A(LDHA),and phospho-fructokinase 1(PFK1)]in the cells of each group,and real-time quantitative fluorescent polymerase chain reaction(qRT-PCR)was used to detect the relative expression levels of mRNA encoding these enzymes.A nude mouse tumor-bearing model was established and divided into control group and Xuanfu Daizhe Decoction-fed group(20 mg/kg)to observe the effect of Xuanfu Daizhe Decoction on the growth of esophageal cancer in vivo.Results The results of CCK-8 assay,wound healing as-say,and Transwell invasion assay showed that Xuanfu Daizhe Decoction could inhibit the prolifera-tion,migration,and invasion activities of EC 109 cells in a concentration-dependent manner.West-ern blot and cellular immunofluorescence analysis revealed that compared with the blank group,the protein expression levels of HK2,LDHA,and PFK1 in the low-concentration,medium-concentra-tion,and high-concentration groups were decreased(P＜0.05).The qRT-PCR results showed that compared with the blank group,the relative expression levels of HK2 mRNA,LDHA mRNA,and PFK1 mRNA in the low-concentration,medium-concentration,and high-concentration groups were all reduced(P＜0.01 or P＜0.000 1).The tumor volume in the subcutaneous tissue on the back of nude mice in the Xuanfu Daizhe Decoction-fed group was smaller than that in the control group,and the protein expression level of LDHA in the tumor tissue of the Xuanfu Daizhe Decoction-fed group was lower than that in the control group,while the expression level of the pro-apoptotic protein Bax was higher than that in the control group(P＜0.05).Conclusion Xuanfu Daizhe Decoction can inhibit the glycolysis process of esophageal cancer cells in a concentration-dependent manner,there-by inhibiting cell proliferation,migration,invasion,and tumor growth in vivo.

Objective To explore the value of T2*mapping in quantitatively evaluate changes in knee joint cartilage and subchon-dral bone of new recruits before and after intensive training.Methods MRI scans of the right knee joint were performed three times on 20 new recruits:before intensive training,after one week of intensive training,and after one month of rest.The knee joint cartilage was divided into six regions:lateral femur(LF),medial femur(MF),lateral tibia(LT),medial tibia(MT),patella cartilage(PC),and trochlea cartilage(TC).Using the posterior angle of the meniscus as a boundary,LF and MF were divided into the cLF/cMF and pLF/pMF.Divid-ed into superficial zone(SZ)cartilage and deep zone(DZ)cartilage based on a thickness of 1/2 of the cartilage.The subchondral bone was divided into superficial bone(SB)within 5 mm of the joint cartilage,and deep bone(DB)within 6-10 mm of the joint cartilage.The T2*values of each region of cartilage and subchondral bone were evaluated through region of interest(ROI)analysis.Single fac-tor analysis of variance was used to compare the changes in T2*values.The LSD test method was used for inter-group comparison.Results After one week of intensive training,MT-SZ,cMF-SZ,PC-SZ,TC-SZ were significantly higher than before intensive training(P＜0.05).After one month of rest,there was no statistically significant difference in the T2*value of the cartilage area compared with before intensive training(P＞0.05).There was a trend of"rising first and then falling".There was no statistically signifi-cant difference in the T2*value of subchondral bone of the knee joint before intensive training and after one week of intensive training(P＞0.05).Compared with after one month of rest,except for cLF-DB,pLF-DB,trochlea cartilage-deep bone(TC-DB),the T2*value of the subchondral bone of the remaining knee joint increased before intensive training and after one week of intensive training,with sta-tistically significant differences(P＜0.05).Conclusion T2*mapping can display the changes in the ultrastructure and biochemical components of joint cartilage and subchondral bone after the new recruits intensive training,detect early injuries and conduct non-invasive quantitative evaluation.

Objective To investigate the dosimetric differences of different types of multileaf collima-tors(MLCs)on the planning target volume(PTV)and organs at risk(OARs)in volumetric modulated arc therapy(VMAT)for cervical cancer.Methods Twenty postoperative patients with cervical cancer receiving radiotherapy in this hospital from May 2023 to January 2024 were selected as the study subjects.For each pa-tient,two kinds of VMAT plans(MLCi2-MLC and AgilityTM-MLC)after cervical cancer operation were de-signed.The dosimetric parameters of the planning target volume(PTV),exposure dose by organs at risk(OAR),y passing rate and monitor units(MU)were compared between the two plans.Results Compared with MLci2-MLC,prescription dose(V45),conformity index(CI)and homogeneity index(HI)in AgilityTM-MLC were better,and the differences were statistically significant(P＜0.05),Compared with MLCi2-MLC,bladder V30,V40,average dose(Dmean),rectal V10,V20,V30,left femoral head V10,Dmean and small intestine V10,V30,Dmean and Dmax were lower,bladder V45,rectal V45,right femoral head V20 were higher,and the differences were statistically significant(P＜0.05).Compared with MLCi2-MLC,the y passing rate in AgilityTM-MLC was lower[(98.31±0.64)％vs.(99.73±0.37)％],and the difference was statistically significant(P＜0.05);while MU had no statistical difference between AgilityTM-MLC and MLCi2-MLC(996.74±65.46 vs.996.80±49.77,P＞0.05).Conclusion AgilityTM-MLC demonstrates better PTV conformity and homogenei-ty,as well as good protection on OARs in both high and low dose regions.

Objective To investigate the clinical characteristics of adult patients with community acquired pneumonia (CAP) caused by acute Mycoplasma pneumoniae (MP) infection, and provide evidence for early identification of MP infection. Methods A prospective, multicenter and cross-sectional study was conducted. 452 adult patients with CAP admitted to Beijing Friendship Hospital, Beijing Guangwai Hospital and Air Force General Hospital from August 2011 to October 2015 were enrolled. The diagnosis of adult MP infection was confirmed by the combined application of double serum antibody titer and MP-DNA nested polymerase chain reaction (PCR) through testing serum and throat swab samples from patients to identify acute infections, past infections, pathogen carrying, and non-MP infection. The clinical characteristics of patients with acute MP infection were summarized by analyzing the baseline data, clinical parameters and chest imaging findings in patients with non-MP infection and acute MP infection. Results Of 452 enrolling patients with CAP, 288 patients (63.7%) suffered from MP infection, and 164 patients (36.3%) with non-MP infection. There were 56 patients (12.4%) with acute infection, 10 patients (2.2%) with past infections, 222 patients (49.1%) with pathogen carriers in MP infective patients indicating susceptible to MP in adult patients. There were no significant differences in gender, age, fever extent, duration of fever, sputum production, shortness of breath, rales, underlying diseases, etc. between non-MP infection and acute MP infection patients, which suggested that the baseline data of the two groups were equilibrium. The acute infection rates of MP in summer and autumn (43.9% and 43.5% respectively) were more than those in spring and winter (13.3% and 12.3% respectively). It was shown by laboratory examination results that serum cardiac troponin T (cTnT) increased significantly in acute MP infectious patients more than that in non-MP infection patients (30.4% vs. 9.8%, P < 0.01), which indicated that patients with acute MP infection were more likely to have myocardial injury. While there were no significant differences in blood routine, blood electrolytes, blood glucose, as well as heart, liver and kidney function between the two groups. It was shown by chest imaging that the diffuse lesions (57.1% vs. 37.2%), mediastinal lymphadenopathy (60.7% vs. 37.8%) were less founded in the middle lobe of the right lung (12.5% vs. 32.9%), which were the main manifestations in patients with acute MP infection as compared with non-MP infection patients with statistical difference (all P < 0.01). There were no significant differences in the chest imaging performances of pulmonary ground glass shadow, lobar and segmental consolidation, patch shadow, a shadow, acinar nodules, grinding glass density nodules, the photic zone, hilar lymphadenopathy and pleural effusion occurrence between the two groups. Conclusion Adult CAP patients are easy to carry MP, myocardial damage is a common complication in acute MP infectious patients which are characteristic of image findings of diffuse lung disease, mediastinal lymphadenopathy and less founded in the middle lobe of the right lung.

BACKGROUND:Previous studies on posterior cervical single door and double door laminoplasty for repair of multilevel cervical myelopathy mainly focus onneurological function and clinical parameters and lack of certain comprehensiveness.
OBJECTIVE:To explore the effects of posterior cervical single door and double door laminoplasty for repair of multilevel cervical myelopathy.
METHODS:We selected 120 patients with multilevel cervical myelopathy and randomly divided into single door group (n=60) and double door group (n=60). The single door group underwent single door laminoplasty. The double door group underwent double door laminoplasty. The blood loss,length of stay, complication rate, neurological function improvement, motion range of cervical vertebrae and imaging changes were compared between the two groups.
RESULTS AND CONCLUSION:(1) Blood loss was significantly less, length of stay was significantly shorter, and the incidence of axial symptom was significantly reduced in the double door group than in the single door group (alP< 0.05). (2) No significant difference in complication rate such as side leakage of cerebrospinal fluid, hematoma, infection and paralysis was detected between the two groups (P> 0.05). The incidence of axial symptoms was significantly less in the double door group than in the single door group (P< 0.05). (3) There were no significant differences in preoperative Japanese Orthopaedic Association scores, postoperative Japanese Orthopaedic Association scores, and improvement in neurological function between the two groups (P> 0.05). Postoperative Japanese Orthopaedic Association scores were significantly increased as compared with that preoperatively in both groups (P<0.05). (4) No significant difference in motion range of cervical vertebrae, inflexion, extension angle and sagittal diameter of spinal canal was detectable between the two groups (P> 0.05). Motion range of cervical vertebrae, extension angle, and inflexion angle were smaler after treatment compared with that preoperatively in both groups (P< 0.05). The increased degree of sagittal diameter of spinal canal was smaler, and the motion range of cervical vertebrae kept better in the double door group than in the single door group. (5) These results indicate that the effect of double door laminoplasty for repair of multilevel cervical myelopathy was significant. The double door laminoplasty can shorten the length of stay, reduce blood loss, axial symptoms, and loss rate of motion range of the cervical vertebrae. In the clinic, treatment can be carried out according to different indications.

Objective To search a new,simple,minimally invasive,safety and effective method to treat the cervical disc herniation.Methods 210 patients with cervical disc herniation received percutaneous nucleoplasty were evaluated.Results They were followed prospectively from two weeks to two months,fifty-nine patients improved significantly,the general clinical effective rate was 96.2%.No complication occurred.Conclusion The percutaneous nucleoplasty is an effective,rapid suited to outpatient,minimally invasive and safe procedure for cervical disc heriation.