G protein-coupled receptors (GPCRs) are the largest family of membrane proteins in eukaryotes, with nearly 800 genes coding for these proteins. They are involved in many physiological processes, such as light perception, taste and smell, neurotransmitter, metabolism, endocrine and exocrine, cell growth and migration. Importantly, GPCRs and their ligands are the targets of approximately one third of all marketed drugs. GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane. However, emerging evidence suggests that GPCRs are also localized on mitochondria, where they play critical roles in modulating mitochondrial functions. These mitochondrial GPCRs (mGPCRs) can influence processes such as mitochondrial respiration, apoptosis, and reactive oxygen species (ROS) production. By interacting with mitochondrial signaling pathways, mGPCRs contribute to the regulation of energy metabolism and cell survival. Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling, highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction. This expanding understanding of mGPCR function on mitochondria opens new avenues for research, particularly in the context of diseases where mitochondrial dysfunction plays a key role. Abnormalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease, diabetes, obesity and Alzheimer's disease. In this review, we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases. We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease, and to underscore their potential as therapeutic targets in the treatment of these conditions.

Objective Based on U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,the signal mining of tizanidine adverse drug events(ADEs)was conducted to explore the occurrence characteristics of ADE,hoping to provide references for the safe clinical application of tizanidine.Methods The reporting odds ratio(ROR)and medicines and healthcare products regulatory agency methods(MHRA)were used to analyse the ADE of tizanidine using FAERS registration data from the first quarter of 2004 to the second quarter of 2022.After valid signals were obtained,the MedDRA was used for translation and system organ classification.Results A total of 7 135 reports of tizanidine ADE were obtained,including 1 732 patients,1 304 ADE types were involved.According to the results of 2 ADE signal mining methods,at the preferred term(PT)level,177 signals were detected.There were 32 PT signals not included in the drug instructions,including potassium wasting nephropathy,cardio-respiratory arrest,and foetal growth restriction etc.In 1 732 patients,the number of ADE cases of female was 2.37 times that in male(1 057 vs.446),and the age group between 40 and 64 accounted for a large proportion(36.03％).The highest proportion(32.79％)reported by consumers.The system organ class involved mainly included various neurological diseases and psychosis.The median time to onset of tizanidine-related ADEs was 75 d(interquartile range:28-223 d),but it was necessary to be vigilant that ADE may still occur 1 year after starting the drug(13.38％).Conclusion This study aims to suggest that clinical application of tizanidin-related ADE should be paid full attention to the occurrence of ADE such as potassium-wasting nephropathy and suicidally completed,as well as key populations such as women and patients of 40-64 years old.

AIM: To study the bioequivalence of two tadalafil tablets in Chinese healthy male subjects. METHODS: A randomized, open-label, two-period, two-sequence, crossover study designing was adopted in the study. Thirty-six healthy male subjects were enrolled under fasting condition and fed condition, respectively. Each subject was given a single oral dose of tadalafil tablet (20 mg). The concentration of tadalafil in plasma was determined by LC-MS/MS. The pharmacokinetic parameters were calculated by WinNonlin 8.0 program, and statistical analysis was performed by using SAS 9.4 statistics software. RESULTS: Under fasting condition, the pharmacokinetic parameters of tadalafil of the test (T) and reference (R) preparation were as follows: C

Objective:To understand the epidemiological and pathogenic characteristics of Legionella in artificial water environment of public places in Shanghai from 2011 to 2018, and to provide scientific basis for the prevention and control of Legionellosis.Methods:A total of 4 817 samples of artificial water environment were collected from 31 public places in Huangpu, Jing′an, Xuhui and Songjiang districts of Shanghai from 2011 to 2108. Epidemiological characteristics of the collected years and months, regional and site types, and sample types were analyzed. After treatment, culture and isolation of the collected water samples, the positive samples were analyzed for Legionella typing characteristics.Results:The positive rate of Legionella pneumophila was 21.57% (1 039/4 817), of which 96.25% (1 000/1 039) was single type, 84.31% (876/1 039) was Legionella pneumophila type 1, followed by Legionella pneumophila type 7 and 6, which accounted for 4.72% (49/1 039) and 3.75% (39/1 039), respectively, and 29 (29/1 039) were multi-type positive. Further typing. From May to October, the highest positive rates were found in July and August, 27.61%(222/804)and 28.61% (230/804)respectively. There were significant differences between different months ( P<0.001); the highest positive rates were found in central air-conditioning cooling water and chilled water (32.40%) and there were significant differences among different water samples ( P<0.001). Legionella pneumophila type 1, type 7 and type 6 were the main diversity distribution characteristics in artificial water environment of different regions, different time, different places and different types of public places. Legionella pneumophila type 1 accounted for the highest proportion, and the proportion of positive samples under different epidemiological characteristics was more than 71.64%. Conclusion:There is relatively serious pollution of Legionella pneumophila type 1 in the artificial water environment of public places in Shanghai. It is necessary to strengthen the disinfection of cooling water/freezing water of central air conditioning in public places in July and August every year.

Objective:To understand the epidemiological and pathogenic characteristics of Legionella in artificial water environment of public places in Shanghai from 2011 to 2018, and to provide scientific basis for the prevention and control of Legionellosis.Methods:A total of 4 817 samples of artificial water environment were collected from 31 public places in Huangpu, Jing′an, Xuhui and Songjiang districts of Shanghai from 2011 to 2108. Epidemiological characteristics of the collected years and months, regional and site types, and sample types were analyzed. After treatment, culture and isolation of the collected water samples, the positive samples were analyzed for Legionella typing characteristics.Results:The positive rate of Legionella pneumophila was 21.57% (1 039/4 817), of which 96.25% (1 000/1 039) was single type, 84.31% (876/1 039) was Legionella pneumophila type 1, followed by Legionella pneumophila type 7 and 6, which accounted for 4.72% (49/1 039) and 3.75% (39/1 039), respectively, and 29 (29/1 039) were multi-type positive. Further typing. From May to October, the highest positive rates were found in July and August, 27.61%(222/804)and 28.61% (230/804)respectively. There were significant differences between different months ( P<0.001); the highest positive rates were found in central air-conditioning cooling water and chilled water (32.40%) and there were significant differences among different water samples ( P<0.001). Legionella pneumophila type 1, type 7 and type 6 were the main diversity distribution characteristics in artificial water environment of different regions, different time, different places and different types of public places. Legionella pneumophila type 1 accounted for the highest proportion, and the proportion of positive samples under different epidemiological characteristics was more than 71.64%. Conclusion:There is relatively serious pollution of Legionella pneumophila type 1 in the artificial water environment of public places in Shanghai. It is necessary to strengthen the disinfection of cooling water/freezing water of central air conditioning in public places in July and August every year.

Objective: To explore the relationship between the level of mental stimulation and the suicide attempts of rural residents in Shandong Province. Methods: A 1:1 matched case-control study was designed to collect 1 200 cases from a survey of three suicide attempts in rural areas of Shandong Province. Controls were selected according to the following matched factors: age difference within 3 years, same gender, same village or neighboring village, no blood relationship, no suicide history. The basic characteristics of all subjects were collected through the questionnaire, and the level of mental stimulation of life events was measured. Multivariate conditional logistic regression model was used to analyze the relationship between the level of mental stimulation of life events and suicide attempts. Results: The mean age of the case group and the control group was both (36.6±0.3) years old, and 35.8% (430/1 200) were males in each group. The low-medium level of mental stimulation of negative life events in the case group was 16.7% (200/1 200) and 61.7% (740/1 200), respectively, which was higher than that in the control group, about 2.5% (30/1 200) and 29.3% (352/1 200) (all P values <0.05), respectively. A total of 11.1% (133/1 200) of the case group had positive life events, which was lower than that of the control group [16.8% (201/1 200)] (all P values<0.05). Multivariate logistic regression model analysis showed that after the adjustment of gender, age, place of residence, education level, marital status, occupation, family income, somatic disease, mental disorders, family history of suicide, and opposite life events, the low-medium and high level of mental stimulation of negative life events were risk factors for suicide attempts, with OR (95%CI) as 5.88 (4.53-7.64) and 13.94 (8.15-23.86), respectively. Mental stimulation of positive life events was protective factor of suicide attempts, with OR (95%CI) as 0.58 (0.41-0.82). Conclusion Mental stimulation of negative and positive life events were risk and protective factors for suicide attempts.

Objective To explore the relationship between the level of mental stimulation and the suicide attempts of rural residents in Shandong Province. Methods A 1:1 matched case?control study was designed to collect 1 200 cases from a survey of three suicide attempts in rural areas of Shandong Province. Controls were selected according to the following matched factors: age difference within 3 years, same gender, same village or neighboring village, no blood relationship, no suicide history. The basic characteristics of all subjects were collected through the questionnaire, and the level of mental stimulation of life events was measured. Multivariate conditional logistic regression model was used to analyze the relationship between the level of mental stimulation of life events and suicide attempts. Results The mean age of the case group and the control group was both (36.6±0.3) years old, and 35.8% (430/1 200) were males in each group. The low?medium level of mental stimulation of negative life events in the case group was 16.7% (200/1 200) and 61.7% (740/1 200), respectively, which was higher than that in the control group, about 2.5% (30/1 200) and 29.3% (352/1 200) (all P values<0.05), respectively. A total of 11.1% (133/1 200) of the case group had positive life events, which was lower than that of the control group [16.8% (201/1 200)] (all P values<0.05). Multivariate logistic regression model analysis showed that after the adjustment of gender, age, place of residence, education level, marital status, occupation, family income, somatic disease, mental disorders, family history of suicide, and opposite life events, the low?medium and high level of mental stimulation of negative life events were risk factors for suicide attempts, with OR (95%CI) as 5.88 (4.53-7.64) and 13.94 (8.15-23.86), respectively. Mental stimulation of positive life events was protective factor of suicide attempts, with OR (95%CI) as 0.58 (0.41-0.82). Conclusion Mental stimulation of negative and positive life events were risk and protective factors for suicide attempts.

Objective To explore the relationship between the level of mental stimulation and the suicide attempts of rural residents in Shandong Province. Methods A 1:1 matched case?control study was designed to collect 1 200 cases from a survey of three suicide attempts in rural areas of Shandong Province. Controls were selected according to the following matched factors: age difference within 3 years, same gender, same village or neighboring village, no blood relationship, no suicide history. The basic characteristics of all subjects were collected through the questionnaire, and the level of mental stimulation of life events was measured. Multivariate conditional logistic regression model was used to analyze the relationship between the level of mental stimulation of life events and suicide attempts. Results The mean age of the case group and the control group was both (36.6±0.3) years old, and 35.8% (430/1 200) were males in each group. The low?medium level of mental stimulation of negative life events in the case group was 16.7% (200/1 200) and 61.7% (740/1 200), respectively, which was higher than that in the control group, about 2.5% (30/1 200) and 29.3% (352/1 200) (all P values<0.05), respectively. A total of 11.1% (133/1 200) of the case group had positive life events, which was lower than that of the control group [16.8% (201/1 200)] (all P values<0.05). Multivariate logistic regression model analysis showed that after the adjustment of gender, age, place of residence, education level, marital status, occupation, family income, somatic disease, mental disorders, family history of suicide, and opposite life events, the low?medium and high level of mental stimulation of negative life events were risk factors for suicide attempts, with OR (95%CI) as 5.88 (4.53-7.64) and 13.94 (8.15-23.86), respectively. Mental stimulation of positive life events was protective factor of suicide attempts, with OR (95%CI) as 0.58 (0.41-0.82). Conclusion Mental stimulation of negative and positive life events were risk and protective factors for suicide attempts.

Objective To establish a gestational diabetes rat model by feeding the rats with high-fat diet.Methods A total of 55 female SD rats were divided into four groups:NV group,NP group,FV group and FP group.Three months after normal feeding,the female rats in NP and FP group were put into the same cage with the male rats at the ratio of 2∶1 and were given high-fat diet or normal diet as usual.Before pregnancy and day 1,7,14,20 in pregnancy,fasting plasma glucose and body weight of rats were detected.The fasting serum insulin and serum c-peptide levels were monitored by enzyme immunoassay and insulin resistance index was calculated.At late pregnancy,glucose tolerance and the indicator of fat were tested.Liver and pancreas were dyed to be observed under microscope.FResultS Body weights of the rats raised with high-fat diet were significantly higher than those of control group and body weight during pregnancy significantly increased (P＜0.05).Fasting glucose,fasting insulin and serum C-peptide in FP group were signifieantly higher than those in NP group and insulin resistance was evident (P＜0.05).The area under curve of GTT in FP group was significantly larger (P＜0.05).The levels of serum lipids in FP group were higher than those in normal group.CorncluSiornS The gestational diabetes rat model induced by high-fat diet can be successfully established.The model presents major pathophysiological manifestations of GDM and can be used as a good model of GDM in relevant research.

Objective To investigate the expression of cystein rich 61 (Cyr61) and vascular endothelial growth factor (VEGF) in different stages of multiple myeloma (MM) patients,evaluate their relationship with angiogenesis and prognosis,and to determine the relationship between Cyr61 and VEGF.Methods Expression of Cyr61 and VEGF in BMMNC from 31 patients with different stages of MM and 10 cases of control were detected by RT-PCR.Results Expression of Cyr61 and VEGF in patients with MM (0.3652±1.5423,0.4815±1.3423) were significantly elevated in comparison to control (0.1862±0.7542,0.2012±1.2331) (P ＜ 0.05,P ＜ 0.01).Expression of Cyr61 and VEGF in stage Ⅲ (0.4632±0.1634,0.5356± 0.2342) was significantly higher than those in stage Ⅰ and stage Ⅱ (t =2.423,2.524,P ＜ 0.05),but there was no difference between stage Ⅰ and stage Ⅱ (0.2513±0.1365,0.3064±0.2124; 0.3084±0.2254,0.3653±0.1265) (t =1.782,1.824,P ＞ 0.05).The levels of Cyr61 and VEGF were significantly decreased after chemotherapy compared to before chemotherapy (P ＜ 0.01).Expression of Cyr61 and VEGF were positively correlated (r =0.8941,P ＜ 0.01).Conclusion Cyr61 and VEGF may play roles in the angiogenesis and pathophysiology of MM.It can be used to guide treatment and estimate prognosis by monitoring Cyr61 and VEGF.