Objective To comparatively analyze the clinical characteristics of primary bilateral macronodular adrenal hyperplasia(PBMAH)and adrenal cortisol-producing Adenoma(CPA),and enhance the understanding of two diseases.Methods The clinical data of 85 PBMAH patients(PBMAH group)and 195 CPA patients(CPA group)diagnosed at Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,from September 2014 to August 2024 were retrospectively analyzed.The demographic characteristics,comorbidities,biochemical indicators,adrenocorticotropic hormone-cortisol(ACTH-F)levels,and adrenal imaging features and treatment conditions were compared between the two groups.Results(1)General characteristics:Compared with CPA group,PBMAH group had older age at diagnosis and a higher proportion of male patients.(2)Clinical characteristics:Compared with CPA group,PBMAH group had a longer disease duration,a higher proportion of subclinical Cushing's syndrome(CS),and a higher proportion of hypertension,impaired glucose tolerance/diabetes,bone mass reduction or osteoporosis,with higher serum potassium levels,and the differences were statistically significant(P<0.01).(3)Hormone levels:Both PBMAH and CPA groups showed ACTH-F rhythm disorder,significantly increased cortisol levels and suppressed ACTH.Compared with PBMAH group,CPA group had stronger autonomous cortisol secretion ability,manifested by increased midnight serum cortisol(F0:00),16:00 serum cortisol(F16:00),24-hour urinary free cortisol(24 h UFC)levels and lower 8:00 serum ACTH(ACTH8:00)and 16:00 serum ACTH(ACTH16:00)(P<0.01).After low-dose dexamethasone suppression test(LDDST),CPA group showed lower suppression rates of ACTH and cortisol,and higher proportions of paradoxical elevation in serum cortisol and 24 h UFC compared with PBMAH(P<0.01).Conclusions PBMAH has a longer disease course and higher proportions of comorbid metabolic disorders than CPA,mostly manifested as subclinical Cushing's syndrome.CPA has stronger autonomous cortisol secretion ability,with cortisol less likely to be suppressed after LDDST and more obvious paradoxical elevation of cortisol and 24 h UFC.

Objective To characterize multimodal metabolic disorders in subclinical Cushing's syndrome(SCS)patients with different cortisol levels,providing a reference for clinical diagnosis and treatment.Methods A retrospective analysis was conducted on the clinical data of 165 SCS patients diagnosed at the First Medical Center of Chinese PLA General Hospital due to adrenal masses from January 2014 to October 2024.Using the serum cortisol levels after the midnight 1 mg dexamethasone suppression test(1 mg DST)as the cut-off point,SCS patients were divided into high-level group(1 mg DST-F>138 nmol/L,n=96)and low-level group(50 nmol/L<1 mg DST-F≤138 nmol/L,n=69).The differences in age,gender,body mass index(BMI),blood pressure,glucolipid metabolism indices,electrolytes,hormone levels,and imaging features of adrenal adenoma(such as CT values)were compared between the two groups.Multivariate linear regression was used to analyze the correlation between CT values and metabolic indices.Results Compared with low-level group,patients in high-level group were younger(54.0±11.3 vs.57.7±10.3,P=0.034),while there were no statistically significant differences in gender ratio or BMI between the two groups(P>0.05).Both groups exhibited decreased adrenocorticotropic hormone(ACTH)levels and disrupted circadian rhythm.Compared with low-level group,high-level group showed significantly higher F0:00 levels[250.00(170.07,422.53)nmol/L vs.110.00(82.74,133.90)nmol/L]and 24-hour urinary free cortisol(24 h UFC)[568.40(377.80,875.45)nmol/24 h vs.369.40(265.40,494.69)nmol/24 h](P<0.001),with no significant differences in serum F8:00,or 1 mg DST ACTH0:00 levels(P>0.05).Except for the fasting C-peptide level in the high-level group being higher than that in low-level group[(2.88±1.01)ng/ml vs.(2.46±0.78)ng/ml,P=0.024],there were no significant differences in blood pressure,blood lipids,glycated hemoglobin(HbA1c),fasting blood glucose,fasting insulin,serum electrolytes,uric acid,and other indices between the two groups(P>0.05).The CT value of adrenal adenoma during contrast-enhanced scanning was higher in high-level group[80.00(17.80,93.00)Hu vs.52.00(35.50,75.00)Hu,P=0.006]compared with low-level group.Multivariate linear regression analysis revealed that diastolic blood pressure was positively correlated with CT values of adrenal adenomas in both plain scanning(β=0.49,95%CI 0.09-0.90)and contrast-enhanced scanning(β=2.08,95%CI 0.76-3.39),while triglyceride levels were negatively correlated with plain scanning CT values(β=-5.77,95%CI-10.88--0.66).Conclusion Patients with SCS at different cortisol levels differ in age,fasting C-peptide levels,and CT values.CT values may serve as potential imaging markers to assess metabolic risk in SCS patients.

Objective To investigate the clinical characteristics of patients with clinical and subclinical Cushing's syndrome caused by primary bilateral macronodular adrenal hyperplasia(PBMAH).Methods A retrospective analysis was performed on the clinical data of 198 patients with Cushing's syndrome caused by PBMAH diagnosed in the First Medical Center of Chinese PLA General Hospital from January 2004 to October 2024.According to clinical manifestations,the patients were classified into clinical type Cushing's syndrome(n=61)and subclinical type Cushing's syndrome(n=137),and the clinical characteristics of the two types were compared.Results The mean age at diagnosis of patients with PBMAH-induced Cushing's syndrome was(53.5±10.4)years,including 118 males and 80 females,with a male-to-female ratio of 1.475:1.Compared with the subclinical type,the clinical type had a higher proportion of females,higher levels of serum cortisol,24-hour urine free cortisol(24 h UFC),and inhibited serum cortisol after low-dose dexamethasone suppression.Additionally,the clinical type had lower plasma ACTH,larger adrenal nodules and a higher risk of surgery(P<0.05)compared with those in subclinical type.The incidences of hypertension,dyslipidemia,obesity,diabetes mellitus,hypokalemia,vitamin D deficiency,osteoporosis,coronary heart disease,and cerebrovascular disease in patients with Cushing's syndrome caused by PBMAH were 87.9%,50.5%,37.1%,36.9%,27.8%,25.9%,18.7%,18.7%and 12.1%,respectively.Among them,compared with subclinical type patients,clinical type patients had higher incidence of hypokalaemia,vitamin D deficiency and osteoporosis(P<0.05),while there were no statistically significant differences in the incidences of other comorbidities between the two types(P>0.05).The results of postoperative follow-up for PBMAH patients showed that the short-term biochemical remission rate of unilateral total adrenalectomy was 41.5%(22/53)and the long-term biochemical remission rate was 32.0%(8/25).The short-term biochemical remission rate of unilateral partial(or nodular)adrenalectomy was 52.9%(9/17),and the long-term biochemical remission rate was 14.3%(1/7).All patients who underwent unilateral total adrenalectomy plus contralateral partial resection developed adrenal insufficiency(3/3),and 1 patient(1/3)relapsed 3.4 years after surgery.Conclusion Clinical and subclinical types of Cushing's syndrome caused by PBMAH have their distinct clinical characteristics.Surgery is an effective treatment for PBMAH,but a certain proportion of patients fail to achieve biochemical remission after non-bilateral total adrenalectomy.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Male infertility is one of the serious problems currently affecting human reproduction and health.Healthy gut microbi-ota is involved in the development of the immune system and protection against pathogen invasion,and it maintain normal metabolism and improve reproductive potential by secreting a variety of substances.The imbalance of gut microbiota can promote the local and sys-temic immune inflammatory response,induce chronic metabolic diseases,affect the synthesis of sex hormones,cause abnormal sper-matogenesis,maturation or activation,and it is closely related to the decline of male fertility.By exploring the correlation between gut microbiota and male infertility,this paper aims to provide new clues and directions for the clinical diagnosis and treatment of male in-fertility.

Objective To investigate the prevalence of Spirometra mansoni infections in hosts in Jiangsu Province, so as to provide the scientific basis for the management of sparganosis mansoni. Methods From 2018 to 2019, nine counties (cities, districts) were randomly selected from Jiangsu Province as the survey sites, and 100 healthy individuals were randomly selected to perform the serological test of S. mansoni infections and the detection of S. mansoni eggs. The procercoids were detected in the intermediate host Cyclops, and the S. mansoni eggs were identified in the stool samples of the definitive hosts cats and dogs. Results The prevalence of S. mansoni human infections was 0 (0/900) in the 9 survey sites of Jiangsu Province, and the sero-prevalence of the specific IgG antibody against S. mansoni was 1.22% (11/900). The positive rate of procercoids was 0.33% (3/900) in Cyclops. In addition, the S. mansoni egg-positive rate was 1.48% (2/135) in cats and dogs. Conclusions Sparganosis mansoni is prevalent in Jiangsu Province. Health education pertaining to the damages of sparganosis mansoni and the route of S. mansoni infections should be improved.

OBJECTIVE: To study the effects of prenatal cold stress on the behavior and mood of offspring in pregnant rats. METHODS: Six SPF-class Wister pregnant rats were randomly divided into normal temperature control group and cold stress group with 3 rats in each group. The pregnant female rats in the normal temperature control group were kept in the environment of (22 ±2)℃, and the pregnant female rats in the cold stress group were placed in the artificial intelligence climate chamber at(4 ±0.1)℃ for 7 days before the birth, and the young rats were divided into normal temperature after the young rats were born. After the young rats were born, they were divided into normal temperature control group of male rats (MR, 22), normal temperature control group of mother rats (FR, 15), cold stress group of male rats (MC, 15), and cold stress group of female rats (FC, 15) .In the fourth generation of the offspring, the open field experiment and the elevated cross maze test were carried out. RESULTS: In the open field experiment, there was no significant difference in spontaneous activity and exploration behavior between the normal temperature control group and the cold stress group (P＞0.05). In the elevated plus maze experiment, the retention time of the open arms, the number of open arms and the distance of the male and female rats in the cold stress group were significantly higher than those in the normal temperature control group (P＜0.05). CONCLUSION Prenatal maternal cold stress has no significant effect on spontaneous activity, exploration behavior and activity level of offspring, but the offspring have obvious abnormal behaviors with reduced anxiety behavior.
Animals ; Anxiety ; Behavior, Animal ; Cold-Shock Response ; Exploratory Behavior ; Female ; Male ; Maze Learning ; Pregnancy ; Prenatal Exposure Delayed Effects ; Random Allocation ; Rats ; Stress, Psychological

Objective To investigate the toxicokinetic properties of ginkgolide B(GB) injection after single or repeat-ed administration by intravenous drip in Beagle dogs and to provide evidence for its rational use. Methods Beagle dogs were randomly divided into three groups,and received GB injection at big,medium and small doses of 80,20 and 5 mg·kg-1, re-spectively,by iv drip for 30 min per day and for 6 consecutive days per week for up to 91 days.The blood samples of Beagle dogs were drawn at different time points on the first and last day of administration,and concentrations in plasma were detected by GC-MS method.Toxicokinetic parameters were calculated by DAS pharmacokinetic software and statistically analyzed by SPSS 11.5 software. Results The elimination half-life (t1/2β) of GB at single dose of 5,20,80 mg·kg-1were(110.2±32.6),(115.4± 12.8),(98.6±26.8) min, respectively.The AUC0-twere (61.1±7.4), (348.6±90.5), (2 046.2±356.4) mg·L-1·min,re-spectively.The t1/2βof GB at mutiple doses of 5,20,80 mg·kg-1on the 91rd day were (117.9±28.0),(118.2±17.0),(120.5± 49.4) min,respectively.The AUC0-twere (67.9±14.9), (218.3±31.8), (1 986.4±426.6) mg·L-1·min, respectively.There was no significant difference in main toxicokinetic parameters including t1/2βamong the single or repeated dosage groups, but AUC0-tand Cmaxincreased proportionally with doses. Conclusion The curves of single and repeated intravenous drip of GB in-jection in beagle dogs were in line with the two atrioventricular model,with linear dynamic characteristics and there was no accu-mulation of repeated drug delivery in the body.

Objective To analyze the feasibility and clinical efficiency of laparoscopic Heller operation combined with Dor fundoplication in the treatment of patients with achalasia of cardia.Methods The clinical materials of 11 patients with achalasia of cardia treated by Heller operation and Dor fundoplication were retrospectively analyzed.Results All the patients successfully completed the operation.The operation time was 85 to 138 min,intra-operative blood loss was 25 to 100 mL,and postoperative hospital stay was 5 to 11 days.One patient had esophageal mucosal rupture,and was treated with repair and suture immediately,and no complications were observed.All the patients were followed up for 3 to 35 months,and the clinical symptoms were significantly relieved.Conclusion Laparoscopic Heller operation combined with Dor fundoplication is safe and effective in the treatment of patients with achalasia of cardia.

Objective To analyze the feasibility and clinical efficiency of laparoscopic Heller operation combined with Dor fundoplication in the treatment of patients with achalasia of cardia.Methods The clinical materials of 11 patients with achalasia of cardia treated by Heller operation and Dor fundoplication were retrospectively analyzed.Results All the patients successfully completed the operation.The operation time was 85 to 138 min,intra-operative blood loss was 25 to 100 mL,and postoperative hospital stay was 5 to 11 days.One patient had esophageal mucosal rupture,and was treated with repair and suture immediately,and no complications were observed.All the patients were followed up for 3 to 35 months,and the clinical symptoms were significantly relieved.Conclusion Laparoscopic Heller operation combined with Dor fundoplication is safe and effective in the treatment of patients with achalasia of cardia.