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 efficacy and safety of simultaneous treatment of small hepatocellular carcinoma(HCC)with transarterial chemoembolization(TACE)combined with cone-beam computed tomography-guided(CBCT-guided)microwave ablation(MWA).Methods The clinical data of 69 patients with small HCC(72 lesions in total),who underwent TACE combined with CBCT-guided MWA simultaneous treatment from March 2018 to December 2022 at First Affiliated Hospital of Soochow University hospital,were retrospectively analyzed.Follow-up check was performed at 1,3,6,and 12 months after treatment.The mRECIST criteria was used to evaluate the tumor response.The objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),local tumor progression(LTP),and adverse reactions were analyzed.Results The initial complete remission(CR)rate,ORR and DCR of TACE combined with CBCT-guided MWA simultaneous treatment for small HCC was 94.2％(65/69),100％and 100％respectively.44.9％(31/69)of patients experienced tumor progression,and 20.3％(14/69)of patients experienced local tumor progression.Univariate and multivariate analyses showed that the maximum tumor diameter(≥2 cm and＜3 cm)was the main risk factor for PFS(HR=4.498,P＜0.001).No serious adverse events occurred during the study.Conclusion TACE combined with CBCT-guided MWA simultaneous treatment for small HCC is clinically effect and safe,and this therapy is particularly suitable for the treatment of lesions where the use of traditional image-guided methods is limited.

OBJECTIVE: To observe the effects of moxibustion at "Shenque" (CV8) on urodynamics and the expression of brain-derived neurotrophic factor (BDNF) and immediate early gene (c-fos) in pontine micturition center (PMC), periaqueductal gray (PAG), medial prefrontal cortex (mPFC) of neurogenic bladder (NB) rats after spinal cord injury. METHODS: Twenty-four SPF female SD rats were randomly divided into a sham-operation group (6 rats) and a modeling group (18 rats). In the modeling group, T₉ complete spinal cord transection method was used to establish a neurogenic detrusor overactivity model, and the 12 rats with successful modeling were randomized into a model group and a moxibustion group, with 6 rats in each group. The rats in the moxibustion group were treated with ginger/salt-insulated moxibustion at "Shenque" (CV8), and 4 consecutive moxa cones were delivered in one intervention. Moxibustion was operated once daily and for 14 days. After intervention completion, the urodynamic indexes of rats in each group were detected. Fluorescence quantitative PCR was used to detect the mRNA expression of BDNF and c-fos in PMC, PAG and mPFC in rats. Western blot was used to detect the protein expression of BDNF and c-fos in PMC, PAG and mPFC. RESULTS: The rats in the sham-operation group did not show phasic detrusor contraction during bladder filling. Compared with the model group, the frequency and amplitude of the phasic detrusor contraction were reduced 5 min before urine leakage in the rats of the moxibustion group (P<0.05), and the duration of the first phasic detrusor contraction during bladder filling was prolonged (P<0.05). Compared with the sham-operation group, the mRNA and protein expression of BDNF and c-fos in PMC, PAG and mPFC increased in the model group (P<0.05). Compared with the model group, the mRNA and protein expression of BDNF and c-fos in PMC, PAG and mPFC decreased in the moxibustion group (P<0.05). CONCLUSION Moxibustion at "Shenque" (CV8) can improve the phasic contraction during bladder filling in NB rats after spinal cord injury, possibly by down-regulating the mRNA and protein expression of BDNF and c-fos in PMC, PAG, and mPFC.
Animals ; Moxibustion ; Female ; Rats ; Brain-Derived Neurotrophic Factor/metabolism* ; Rats, Sprague-Dawley ; Acupuncture Points ; Spinal Cord Injuries/metabolism* ; Urinary Bladder, Neurogenic/etiology* ; Proto-Oncogene Proteins c-fos/metabolism* ; Humans ; Urinary Bladder/physiopathology* ; Brain/metabolism* ; Urination

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective:To evaluate the effect of robot-assisted laparoscopic technology via abdominal approach for patients with primary retroperitoneal tumors.Methods:A retrospective cohort analysis was conducted for the clinical data of 71 patients who underwent robot-assisted laparoscopic resection of primary retroperitoneal tumor via abdominal approach at the Department of Urology of Sir Run Run Shaw Hospital,Zhejiang University School of Medicine from January 2015 to December 2023. There were 35 male and 36 female patients. The age ( M(IQR)) was 56(21) years (range: 21 to 83 years). The median tumor diameter was 46 (31) mm (range: 15 to 134 mm). Postoperative pathology revealed 58 benign and 13 malignant cases. Patients were divided into non-adherent group ( n=47) and adherent group ( n=24) based on whether the tumor was adhered to major organs or vessels. Perioperative and postoperative situation were compared between the two groups. Data comparisons were conducted using independent samples t-test for normally distributed continuous variables, Mann-Whitney U tests for non-normally distributed data, χ2 test or Fisher′s exact test for categorical variables. Kaplan-Meier survival analysis was employed to estimate 3-year recurrence or metastasis rate and 3-year mortality rate. Results:Operative time was 120(60) minutes (range: 45 to 440 minutes), intraoperative blood loss was 50 (80) ml (range: 10 to 2 000 ml). The median change of intraoperative mean arterial pressure was 40 (19) mmHg(1 mmHg=0.133 kPa)(range: 10 to 112 mmHg). Intraoperative blood transfusion was required in 7 cases, whereas 64 cases did not necessitate transfusion. The change in hemoglobin levels before and after surgery was (17.9±13.6) g/L (range:-16 to 53 g/L), and the median change in serum creatinine levels was 2.0 (14.5) μmol/L (range:-71.0 to 100.4 μmol/L). Postoperative fasting duration was 2.0 (1.5) days (range: 1 to 6 days), and the median hospital stay was 10.0 (7.5) days (range: 4 to 24 days). No perioperative mortality occurred in any of the patients. The non-adherent group had shorter operation time, less estimated blood loss, lower blood transfusion rate, smaller delta value of hemoglobin before and after surgery, larger delta value of creatinine before and after surgery, fewer postoperative complications, shorter postoperative fasting time, and shorter length of hospital stay than the adherent group(all P<0.05), while there was no significant difference in mean arterial pressure fluctuation between the two groups ( P>0.05). Follow-up data were available for 69 patients, with a median follow-up duration of 39 (43) months (range: 4 to 88 months). Among these patients, 40 completed the 3-year follow-up. The 3-year recurrence or metastasis rate was 10.14%, and the 3-year mortality rate was 2.90%. Conclusions:Robot-assisted laparoscopic technology via abdominal approach for resection of primary retroperitoneal tumors is safe and feasible. It can also achieve secure surgical outcome for primary retroperitoneal tumors adherent to surrounding organs or vessels, albeit with increased surgical complexity and slower postoperative recovery compared to non-adherent cases.

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.