Objective To evaluate the bioequivalence of a single oral dose of ritonavir in fasted and fed conditions in healthy Chinese adult subjects with the test and reference formulations.Methods A single-center,open-label,randomized,single-dose,two-periods,two-sequence crossover design was used,and 64 subjects were enrolled in both the fasted and fed groups.The subjects received 100 mg of the test preparation or reference preparation orally per cycle,and the drug concentration of ritonavir in plasma was detected using the high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method.Pharmacokinetic parameters were estimated by a non-compartment model,and SAS 9.4 software was used for statistical analysis.Results Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of ritonavir tablets and the reference formulation in the fasting group:Cmax were(791.90±400.20)and(809.60±449.14)ng·mL-1;AUC0_t were(6 072.61±2 631.98)and(6 296.30±3 388.95)ng·h·mL-1;AUC0-∞ were(6 129.59±2 655.57)and(6 347.26±3 434.12)ng·h·mL-1,respectively.Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of ritonavir tablets and the reference formulation in the fed group:Cmax were(512.37±233.60)and(521.74±223.87)ng·mL-1;AUC0_t were(4 203.43±2 221.33)and(4 200.13±1 993.50)ng·h·mL-1;AUC0_∞ were(4 259.21±2 266.88)and(4 259.63±2 044.12)ng·h·mL-1.The 90％confidence intervals for the geometric mean ratios of Cmax,AUC0_t and AUC0_∞ of the prototype drug ritonavir in plasma after oral administration of 100 mg of the test and reference formulations of ritonavir tablets under fasting and fed conditions fell within the 80.00％to 125.00％equivalence interval.Conclusion The test and reference formulations of ritonavir tablets were bioequivalent under fasting and postprandial conditions.

Objective:To investigate the current status of scientific fitness literacy (SFL) and its influencing factors among Chinese adults aged 20-59 years.Methods:Totally 63 338 adults aged 20-59 years in the status of national fitness activities in 2020 from 1 January to 31 March 2020 were selected as the subjects, and they were divided into four age groups, namely, the 20-29 age group, the 30-39 age group, the 40-49 age group and the 50-59 age group. Data were analyzed by SPSS 29.0.Comparative analyses for age, gender, urban-rural difference were carried out by applying non-parametric tests, and multiple regression models were applied to find the influencing factors of SFL.Results:The SFL score of Chinese adults aged 20-59 years was 53.40 (41.67, 63.73), and the scores of cognition, attitude, ability and skills, behavior and habits sub-dimensions were 86.11 (72.22, 100.00), 62.96 (50.62, 75.31), 27.78 (11.11, 44.44) and 33.33 (11.11, 55.56), respectively. The SFL and the four sub-dimensions were demonstrated to have higher scores for males than females, and higher scores for adults in urban area than those in rural area(all P<0.01). The multiple regression results showed that regular exercise at a fitness facility (20-29 age group: β=0.321, t=5.940, P<0.01; 30-39 age group: β=0.187, t=2.937, P<0.01; 40-49 age group: β=0.230, t=3.988, P<0.01; 50-59 age group: β=0.415, t=5.671, P<0.01) was the Chinese adults' common influence factor on SFL.Motivation, evaluation by those around them, experience from exercising, and convenience and atmosphere of exercising were the main influence factors in the 20-29 and 30-39 age groups(all P<0.05).Comfort level of fitness venue, convenience, safety, and support of fitness place were the main influence factors in adults aged 40-59 years(all P<0.05). Conclusions:Chinese adults aged 20-59 years old have high SFL awareness scores, but low overall SFL scores. Surrounding people's evaluation, experience in exercise, comfort level of fitness place, convenience, safety and fitness policy support are the influential factors of scientific fitness literacy.

Objective:To explore the effect and safety of mesenchymal stem cell exosome microneedle introduction in the treatment of melasma.Methods:Thirty cases of female patients with stable melasma in the Department of Dermatology, Changsha Meilai Medical Beauty Hospital, aged (36±5) years and with a disease duration of (42.4±20.7) months, from July 2021 to July 2022, were retrospectively included. According to Fitzpatrick skin typing, 23 cases of type Ⅲ and 7 cases of type Ⅳ were included. All patients were locally anesthetized with lidocaine cream for 30 min, and rolled with a 0.5 mm needle in a zigzag pattern with even force, in the order of the right cheek, the left cheek, the forehead, the nose, the mandible, and the upper lip. During the rolling process, 3 ml of MSC exosome medical liquid wound dressing was applied to the facial skin, and after it was fully absorbed, exosome was locally readministered in the area of melasma. Treatment ended with a slight redness at the site of application. 1 MSC exosome wound dressing was appllied as a cold compress for 15 min after treatment. Treatment was given once every 2 weeks for 6 consecutive sessions. All the patients were followed up at 4 and 12 weeks after the last session, and the area and severity index of melasma (MASI) were scored before and after the treatment, the clinical efficiency and patient satisfaction rate and the incidence of adverse reactions were also counted.Results:At 4 and 12 weeks after the end of treatment, the skin color of all 30 patients was brighter than that before treatment, and no recurrence of melasma symptoms seen. At 12 weeks after the end of treatment, the decrease rate of MASI score was 66.1%, among which the decrease rate of MASI score in patients with type Ⅲ melasma was 63.9%, and the decrease rate of MASI score in patients with type Ⅳ melasma was 63.9%. Among the 30 patients, 1 case was cured, 25 cases showed obvious improved, 4 cases were improved, and no cases were ineffective, with an effective rate of 86.7% (26/30). Five patients were very satisfied, 18 patients were satisfied, 6 patients were generally satisfied, and 1 patient was dissatisfied; the patient satisfaction rate was 76.7% (23/30). No serious adverse reactions occurred in all patients.Conclusions:MSC exosome microneedle introduction is safe and effective in the treatment of melasma without serious adverse reactions.

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

China ; History of Medicine ; Medicine/standards*

This paper aimed to investigate the role and potential mechanism of p53 on primordial follicle activation. Firstly, the p53 mRNA expression in the ovary of neonatal mice at 3, 5, 7 and 9 days post-partum (dpp) and the subcellular localization of p53 were detected to confirm the expression pattern of p53. Secondly, 2 dpp and 3 dpp ovaries were cultured with p53 inhibitor Pifithrin-μ (PFT-μ, 5 μmol/L) or equal volume of dimethyl sulfoxide for 3 days. The function of p53 in primordial follicle activation was determined by hematoxylin staining and whole ovary follicle counting. The proliferation of cell was detected by immunohistochemistry. The relative mRNA levels and protein levels of the key molecules involved in the classical pathways associated with the growing follicles were examined by immunofluorescence staining, Western blot and real-time PCR, respectively. Finally, rapamycin (RAP) was used to intervene the mTOR signaling pathway, and ovaries were divided into four groups: Control, RAP (1 μmol/L), PFT-μ (5 μmol/L), PFT-μ (5 μmol/L) + RAP (1 μmol/L) groups. The number of follicles in each group was determined by hematoxylin staining and whole ovary follicle counting. The results showed that the expression of p53 mRNA was decreased with the activation of primordial follicles in physiological condition. p53 was expressed in granulosa cells and oocyte cytoplasm of the primordial follicles and growing follicles, and the expression of p53 in the primordial follicles was higher than that in the growing follicles. Inhibition of p53 promoted follicle activation and reduced the primordial follicle reserve. Inhibition of p53 promoted the proliferation of the granulosa cells and oocytes. The mRNA and protein expression levels of key molecules in the PI3K/AKT signaling pathway including AKT, PTEN, and FOXO3a were not significantly changed after PFT-μ treatment, while the expression of RPS6/p-RPS6, the downstream effectors of the mTOR signaling pathway, was upregulated. Inhibition of both p53 and mTOR blocked p53 inhibition-induced primordial follicle activation. Collectively, these findings suggest that p53 may inhibit primordial follicle activation through the mTOR signaling pathway to maintain the primordial follicle reserve.
Female ; Animals ; Mice ; Tumor Suppressor Protein p53/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Hematoxylin ; Signal Transduction/physiology* ; TOR Serine-Threonine Kinases ; Sirolimus ; RNA, Messenger

OBJECTIVE: To investigate the gene mutation and genotype distribution of thalassemia in the population of childbearing age in Chongzuo area of Guangxi. METHODS: Six α-thalassemia and 17 β-thalassemia gene mutations common in Chinese were detected by gap-polymerase chain reaction (gap-PCR) combined with agarose gel eletrophoresis and reserve dot bolt hybridization in 29 266 cases of child-bearing age suspected of thalassemia. RESULTS: A total of 19 128 (65.36%) cases were identified with thalassemia. The detection rate of α-thalassemia, β-thalassemia and α-combining β-thalassemia was 45.25% (13 242/29 266), 15.47% (4 526/29 266) and 4.65% (1 360/29 266), respectively. A total carrying rate of 8 kinds of α-thalassemia gene mutations was 26.74% (15 649/58 532), including 12.51% for --^SEA, followed by 5.70% for -α^3.7, and 0.24% for --^Thai. Among 32 α-thalassemia genotypes, the most common five were --^SEA/αα, -α^3.7/αα, α^CSα/αα, -α^4.2/αα and α^WSα/αα, accounting for 47.27%, 18.31%, 8.56%, 8.52% and 7.91%, respectively, as well as 0.97% for --^Thai/αα. A total carrying rate of 13 kinds of β-thalassemia gene mutations was 10.07% (5 897/58 532), including 3.63% for CD41-42, followed by 2.55% for CD17, and 0.003% for -50 (G>A). Among 17 β-thalassemia genotypes, the most common six were CD41-42/N, CD17/N, CD71-72/N, CD26/N, 28/N and IVSI-1/N, accounting for 36.15%, 25.81%, 9.43%, 8.18%, 8.09% and 7.75%. The homozygous genotype CD26/CD26 [hemoglobin (Hb): 121 g/L] and -28/-28 (Hb: 56 g/L) were respectively detected in one case, and double heterozygous genotype were detected in 5 cases, including 3 cases of CD41-42/CD26 (Hb: 41 g/L, 51 g/L, 63 g/L, respectively), 1 case of -28/IVSI-1 (Hb: 53 g/L), and 1 case of CD71-72/CD26 (Hb: 89 g/L), in which patients with moderate or severe anemia had a history of blood transfusion. Among 104 α-combining β-thalassemia genotypes, the most common were --^SEA/αα, -α^3.7/αα combining CD41-42/N and --^SEA/αα combining CD17/N, accounting for 12.13%, 9.63% and 9.26%, respectively. In addition, 1 case of --^SEA/-α^3.7 combining -28/IVSI-1 (Hb: 83 g/L) and 1 case of -α^3.7/αα combining CD41-42/ CD41-42 (Hb: 110 g/L) were detected without history of blood transfusion, while 1 case of α^WSα/αα combining CD41-42/CD17 (Hb: 79 g/L) and 1 case of --^SEA/αα combining CD17/-28 (Hb: 46 g/L) were detected with history. CONCLUSIONS The detection rate of thalassemia genes is high and the mutations are diverse in the population of childbearing age in Chongzuo area of Guangxi. The common deletion genotype is --^SEA/αα in α-thalassemia and CD41-42/N in β-thalassemia, and deletion genotype --^Thai is not rare. There is a certain incidence of intermediate and severe β-thalassemia, and most patients require transfusion therapy. The results are beneficial for genetic consultation and intervention of thalassemia.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Dipeptidyl Peptidase 4/genetics* ; China/epidemiology* ; Genotype ; Mutation

Objective To investigate the release of enterogenic and hepatogenic high mobility group protein B1(HMGB1)through exosomes and its regulatory pathway.Methods We used wild-type(WT)and ASC-/-mice for this study.We randomly selected five mice per group from each strain and fed them either a normal diet(ND)or a high-fat diet(HFD)for eight weeks.The control group consisted of WT mice fed with the normal diet;the HFD group were WT mice with the HFD;the microflora disturbance(MD)group were ASC-/-mice fed with the normal diet;the high-lipid microflora disturbance(HLMD)group were ASC-/-mice with HFD.We used confocal microscopy to detect the co-localization of liver and intestinal exosome markers with HMGB1.We then measured the expression level of HMGB1 content in exosomes by Western blotting and PCR.The AML12 cells were treated with palmitic acid(PA)and lipopolysaccharide(LPS)for 24 h to build an in vitro model.We also detected HMGB1/CD63 levels using Western blotting.To understand the regulatory mechanism of exosome release,we employed siRNA intervention.Results The secretion of exosomes increased significantly in HFD group compared with control group[(3.5±0.2)ng/ml vs.(1.1±0.3)ng/ml,P<0.05],HLMD group compared with those in MD group[(3.2±0.2)ng/ml vs.(1.9±0.4)ng/ml,P<0.05].Using immunofluorescence detection,we observed increased co-localization of exosome markers(ALP or VPS16)with HMGB1 in HFD group compared with control group.We also observed this in AML12 cells treated with PA and LPS compared with blank control.The PCR data showed that HMGB1 in hepatocyte exosomes was higher in HFD group compared with control group(41.5±10.2 vs.1.3±0.3,P<0.05),HLMD group was significantly higher than that in MD group(48.6±7.2 vs.1.5±0.5,P<0.05).TLR4 expression was higher in HFD group compared with control group(13.8±6.2 vs.2.8±0.9,P<0.05),HLMD group compared with MD group(22.6±4.1 vs.2.5±1.5,P<0.05).In intestinal mucosal cells,the co-location of HMGB1 and exosome marker CD63 was significantly higher in HFD group compared with control group(0.6±0.2 vs.0.4±0.1,P<0.05),and HLMD group compared with MD group(0.9±0.2 vs.0.5±0.1,P<0.05).In vitro,the HMGB1 of exosomes was increased in endotoxin group(5.1±0.8)and high lipid endotoxin group(5.5±0.7)compared with control group(3.8±0.6,P<0.05).On the other hand,the HMGB1 of exosomes in the cell siRNA intervention group was not increased compared with control group(3.7±0.6 vs.3.8±0.6,P>0.05).Conclusion HMGB1 is released by exosomes in hepatocytes and intestinal cells,and regulated by Toll-like receptor 4(TLR4)under a high-fat diet and intestinal flora disorder,which may be one of the contributing factors in promoting the development of steatohepatitis.

Objective:To analyze the safety and efficacy of left atrial appendage closure(LAAC)with Watchman in patients ≥85 years with atrial fibrillation(AF).Methods:515 elderly patients with atrial fibrillation, including 73 patients aged 85 years or older(85~91), who had undergone Watchman LAAC at Zhoupu Hospital affiliated to Shanghai Health Medical College from August 2016 to December 2020, were retrospectively analyzed.Of those ≥85 years, 44(60.3%)with transesophageal echocardiography records were assigned to the elderly group.Fifty-three patients aged 60 to 65 were selected as the control group.Differences in baseline data, intraoperative conditions, antithrombotic treatment plans and 1-year follow-up prognosis were compared between the two groups.Results:Compared with the control group, there was no difference in AF types, history of ischemic stroke/transient ischaemic attack(all P>0.05), but there were higher incidences of coronary heart disease and renal insufficiency, more severe heart failure, higher CHA 2DS 2-VASC(6.0±1.5 vs.3.6±1.5), HAS-BLED(3.2±1.2 vs.2.3±1.3)scores( t values were 7.682 and 3.871, respectively, P<0.05), and a lower one-stop surgery rate(6 cases or 13.6% vs. 27 cases or 50.9%, χ2=10.517, P<0.05)in the advanced age group.There was no difference in the diameter of the Watchman device, rate of device replacement, compression percentage and residual flow between the two groups during the perioperative period.The incidences of device-related thrombosis were 4.5%(2/44)and 3.8%(2/53)for the advanced age group and the control group, respectively, but the difference was not statistically significant( P>0.05). During the 12-month follow-up, there were no cases of ischemic stroke or intracerebral hemorrhage.Three died of heart failure and 1 died of cancer. Conclusions:LAAC with Watchman is safe and effective for patients over 85 years with AF, but the decision on the procedure should be based on careful assessment of patients' cardiac and renal function and general health.

Animals ; Biological Assay ; Nucleic Acid Amplification Techniques ; Phlebovirus/isolation & purification* ; Psychodidae/virology* ; Recombinases/metabolism* ; Reverse Transcription