Objective To elucidate how the overexpression of cystathionine-β-synthase(CBS)plays an antihypertensive role by affecting peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α)expression.Methods The adeno-associated viruses(AAVs),ones that overexpressed CBS,and another knocked down PGC-1α,were injected into the hypothalamic paraventricular nucleus(PVN)of spontaneously hypertensive rats(SHRs).The rats'blood pressure was monitored,and the level of norepinephrine(NE)was examined by ELISA;PVN inflammatory response,oxidative stress and tyrosine hydroxylase(TH)expression were detected with RT-qPCR and immunofluorescence.Results PVN overexpression of CBS could increase the transcription level of CBS(by 3.8 times,P＜0.05)and PGC-1α(by 1.6 times,P＜0.05)in PVN of SHR.PVN overexpression of CBS could reduce blood pressure in SHR(from 177.81 mmHg to 128.77 mmHg,P＜0.001),but PVN knockdown of PGC-1αweakened such effect(from 128.77 mmHg to 152.79 mmHg,P＜0.05).PVN overexpression of CBS could alleviate PVN inflammatory response and oxidative stress,but this effect was weakened or even eliminated when knocking down PGC-1α was performed at the same time.Conclusion PVN overexpression of CBS can reduce blood pressure in SHR,and this effect may be achieved by increasing the transcriptional level of PGC-1α,alleviating PVN inflammatory response,oxidative stress,and improving sympathetic nerve excitation.

Objective:To investigate the clinical effect of the divisional design in composite labia minora and clitoral hood reduction.Methods:A retrospective analysis was performed on 57 patients diagnosed with labia minora and clitoral hood hypertrophy at Department of Plastic Surgery, Nanjing Medical University Friendship Plastic Surgery Hospital between July 2018 and May 2021. The ages of the patients ranged from 24 to 45 years with an average of (31.0±8.2) years. Preoperative symptoms and surgical demands included: appearance concerns in 57 cases (100%), irritation during friction in 49 cases (86.0%), and discomfort during intercourse in 22 cases (38.6%). The complex hypertrophy was divided into simple labia minora hypertrophy and clitoral hood hypertrophy. Then the reduction of clitoris hood was performed according to the prepuce morphology, and labiaplasty was performed using edge resection. The operative effects, patient satisfaction, and postoperative complications were assessed.Results:All incisions healed primarily with no flap necrosis or marginal infections. Hematoma occurred in 1 case which recovered well after timely treatment. All patients were followed up for 3-12 months. 54 cases were satisfied with the labia minora and clitoral hood shape and reported no sensory abnormality. Bilateral asymmetry occurred in 2 cases, one of which required further surgical repair. Scar hyperplasia occurred and was gradually softened after 6 months in 1 case. Of the 57 patients with appearance concerns, 55 (96.5%) patients reported improved appearance postoperatively. Of the 49 patients with preoperative friction discomfort, 47 (95.9%) patients achieved symptom relief. Of the 22 patients reporting sexual discomfort, 15 (68.1%) patients noted enhanced sexual satisfaction postoperatively. Overall, 54 (94.7%) patients were satisfied, 2 (3.5%) patients were moderately satisfied, and 1 (1.8%) patient was unsatisfied.Conclusions:For patients with labia minora and clitoral hood hypertrophy, the application of divisional design is surgically simple and safe. It achieves satisfactory outcomes with no severe adverse reactions.

Objective To elucidate how the overexpression of cystathionine-β-synthase(CBS)plays an antihypertensive role by affecting peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α)expression.Methods The adeno-associated viruses(AAVs),ones that overexpressed CBS,and another knocked down PGC-1α,were injected into the hypothalamic paraventricular nucleus(PVN)of spontaneously hypertensive rats(SHRs).The rats'blood pressure was monitored,and the level of norepinephrine(NE)was examined by ELISA;PVN inflammatory response,oxidative stress and tyrosine hydroxylase(TH)expression were detected with RT-qPCR and immunofluorescence.Results PVN overexpression of CBS could increase the transcription level of CBS(by 3.8 times,P＜0.05)and PGC-1α(by 1.6 times,P＜0.05)in PVN of SHR.PVN overexpression of CBS could reduce blood pressure in SHR(from 177.81 mmHg to 128.77 mmHg,P＜0.001),but PVN knockdown of PGC-1αweakened such effect(from 128.77 mmHg to 152.79 mmHg,P＜0.05).PVN overexpression of CBS could alleviate PVN inflammatory response and oxidative stress,but this effect was weakened or even eliminated when knocking down PGC-1α was performed at the same time.Conclusion PVN overexpression of CBS can reduce blood pressure in SHR,and this effect may be achieved by increasing the transcriptional level of PGC-1α,alleviating PVN inflammatory response,oxidative stress,and improving sympathetic nerve excitation.

Objective:To investigate the clinical effect of the divisional design in composite labia minora and clitoral hood reduction.Methods:A retrospective analysis was performed on 57 patients diagnosed with labia minora and clitoral hood hypertrophy at Department of Plastic Surgery, Nanjing Medical University Friendship Plastic Surgery Hospital between July 2018 and May 2021. The ages of the patients ranged from 24 to 45 years with an average of (31.0±8.2) years. Preoperative symptoms and surgical demands included: appearance concerns in 57 cases (100%), irritation during friction in 49 cases (86.0%), and discomfort during intercourse in 22 cases (38.6%). The complex hypertrophy was divided into simple labia minora hypertrophy and clitoral hood hypertrophy. Then the reduction of clitoris hood was performed according to the prepuce morphology, and labiaplasty was performed using edge resection. The operative effects, patient satisfaction, and postoperative complications were assessed.Results:All incisions healed primarily with no flap necrosis or marginal infections. Hematoma occurred in 1 case which recovered well after timely treatment. All patients were followed up for 3-12 months. 54 cases were satisfied with the labia minora and clitoral hood shape and reported no sensory abnormality. Bilateral asymmetry occurred in 2 cases, one of which required further surgical repair. Scar hyperplasia occurred and was gradually softened after 6 months in 1 case. Of the 57 patients with appearance concerns, 55 (96.5%) patients reported improved appearance postoperatively. Of the 49 patients with preoperative friction discomfort, 47 (95.9%) patients achieved symptom relief. Of the 22 patients reporting sexual discomfort, 15 (68.1%) patients noted enhanced sexual satisfaction postoperatively. Overall, 54 (94.7%) patients were satisfied, 2 (3.5%) patients were moderately satisfied, and 1 (1.8%) patient was unsatisfied.Conclusions:For patients with labia minora and clitoral hood hypertrophy, the application of divisional design is surgically simple and safe. It achieves satisfactory outcomes with no severe adverse reactions.

Objective:To compare the diagnostic efficacy of 68Ga-PSMA-11 PET/ CT and multi-parameter magnetic resonance imaging (mpMRI) for pelvic lymph node metastases in prostate cancer patients who received neoadjuvant endocrinology or not after initial diagnosis. Methods:Data of 52 patients with moderate and high-risk prostate cancer admitted to Xijing Hospital from February to October 2023, aged (65.8±6.6) years, preoperative prostate-specific antigen (PSA) 26.67 (13.09, 84.89) ng/ml, were retrospectively analyzed. Before operation, there were 28 cases of cT 2stage, 16 cases of cT 3 stage and 8 cases of cT 4 stage. There were 22 cases of cN 0 and 30 cases of cN 1. All patients underwent 68Ga-PSMA-11 PET/CT and mpMRI at the same time, and were diagnosed positive lymph nodes in 28 and 21 cases, respectively. Risk stratification were high risk in 45 cases, and medium risk in 7 cases. According to the preoperative endocrine treatment, they were divided into the newly diagnosed group without treatment (24 cases) and the endocrine treated group (28 cases), whose ages were (65.0±7.1) years and (66.8±6.1) years, respectively. Preoperative PSA was 26.17 (16.73, 61.18) ng/ml and 27.32 (11.94, 130.18) ng/ml, respectively. Gleason scores ≤7 were in 10 cases (41.7%) and 6 cases (21.4%), and Gleason scores >7 were in 14 cases (58.3%) and 22 cases (78.6%), respectively. There were 15 (62.5%) and 13 (46.4%) cases of cT 1-2 stage, and 9 (37.5%) and 15 (53.6%) cases of cT 3-4 stage, respectively. There were 16 (66.7%) and 6 (21.4%) cases of stage N 0, 8 (33.3%) and 22 (78.6%) cases of stage N 1, respectively. There were 22 (91.7%) and 20 (71.4%) cases of stage M 0, 2 (8.3%) and 8 (28.6%) cases of stage M 1, respectively. PET/CT diagnosis of lymph node positive was in 9 cases (37.5%) and 19 cases (67.9%), and mpMRI diagnosis of lymph node positive was in 5 cases (20.8%) and 16 cases (57.1%). The number of positive lymph nodes diagnosed by PET/CT was 13 (72.2%) and 47 (90.1%), and the number of positive lymph nodes diagnosed by mpMRI was 8 (44.4%) and 32 (61.5%). There was no significant difference ( P>0.05). All patients underwent radical prostatectomy as well as enlarged pelvic lymph node resection. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the two imaging examinations in the diagnosis of lymph node metastasis were compared according to the results of postoperative pathological examination of lymph nodes. Receiver operating characteristic (ROC) curve was used to compare the accuracy of the two imaging tests in the diagnosis of pelvic lymph node metastasis in the newly diagnosed untreated group and the endocrine treated group. Results:In this study, of 52 cases, 26 (50.0%) had positive lymph nodes by pathological examination. In this study, a total of 681 lymph nodes were dissected, with 70 lymph nodes (10.28%) being pathologically positive, and the positive rate of 26 patients was 17.99% (70/389). The PET/CT and mpMRI detection rates of 26 node-positive patients were 92.3% (24/26) and 57.7% (15/26), respectively. There were 9 (37.5%) and 17 (60.7%) lymph node positive patients in the untreated group and the endocrine therapy group, respectively. There were 320 and 361 lymph nodes were clear, with 18 (5.6%) and 52 (14.4%) positive lymph nodes, respectively. The detection rates of PET/CT and mpMRI were 88.89% (8/9) and 94.12% (16/17)in the untreated group, and 44.44% (4/9) and 64.71% (11/17)in the endocrine treated group, respectively. In the newly treated group, the area under the curve (AUC) of PET/CT and mpMRI for diagnosing positive lymph nodes were 0.911 and 0.689 ( P=0.027), the sensitivity were 88.9% and 44.4%, and the specificity were 93.3% and 93.3%, respectively. PPV were 88.9% and 80.0%, and NPV were 93.3% and 73.7%, respectively. In the endocrine therapy group, the AUC of PET/CT and mpMRI for lymph node positive diagnosis were 0.834 and 0.596 ( P=0.011), the sensitivity were 94.1% and 64.7%, the specificity were 72.7% and 54.5%, and the PPV were 84.2% and 68.8%, respectively. NPV were 88.9% and 50.0%, respectively. Conclusions:For prostate cancer patients, regardless of whether they receive neoadjuvant endocrine therapy, 68Ga-PSMA-11 PET/CT can accurately detect pelvic lymph node metastasis, and the diagnostic efficacy is significantly better than that of mpMRI.

Objective:To study the efficacy of 68Ga-PSMA PET/CT in evaluating lymph node metastases (LNMs) in patients with prostate cancer (PCa). Methods:Patients who recieved 68Ga-PSMA PET /CT examination in the First Affiliated Hospital of Air Force Military Medical University from July 2021 to February 2022 were enrolled. The patients’ age was (64.4±6.1) years old, with median total prostate specific antigen (tPSA) 34.5 (6.1-99.0) ng/ ml, including PSA<10ng/ ml in 12 cases, 10-20ng/ ml in 21 cases, and > 20 ng/ml in 25 cases. Preoperative clinical staging: 1 case in T 1 stage, 38 cases in T 2 stage, 16 cases in T 3stage, 3 cases in T 4 stage. Preoperative Gleason score of 10 cases was <7, 20 cases was 7, and 28 cases was > 7. According to D 'Amico risk grouping criteria, there were 8 cases in the low-risk group, 20 cases in the medium-risk group and 30 cases in the high-risk group. Preoperative examination of 68Ga-PSMA PET/CT showed no distant metastasis such as visceral metastasis and bone metastasis. All patients underwent radical prostatectomy and pelvic lymph node dissection. The following patients were excluded: patients received preoperative prostate surgery, patients received endocrine therapy, chemotherapy and radiotherapy for prostate cancer before surgery, a history of other malignant tumors in the past 2 years, biopsy pathological diagnosis of neuroendocrine cell prostate cancer and other special types of prostate cancer, prior history of major pelvic surgery, etc. Radical prostatectomy was performed. 38 patients received laparoscopic surgery and 20 patients received robot-assisted laparoscopic surgery. The sensitivity and specificity of 68Ga-PSMA PET /CT for the diagnosis of lymph node metastasis of prostate cancer were calculated according to the comparison of lymph node metastasis in postoperative pathological results and preoperative examination. Results:Postoperative pathological diagnosis: Gleason score of 9 cases was <7, 19 cases was 7, and 30 cases was >7. 37 cases were in pT 2 stage, 17 cases in pT 3 stage, and 4 cases in T 4 stage. There were 12 cases (20.7%) of positive resection margin, and 7 cases (12.1%) of lymphatic fistula. There were 10 patients with lymph node metastasis diagnosed by 68Ga-PSMA PET/CT before surgery, and 17 positive lymph node regions. A total of 11 patients were pathologically positive in lymph nodes, and a total of 20 lymph nodes regions were positive. Based on the number of patients, the specificity and sensitivity of 68Ga-PSMA PET /CT in diagnosing lymph node metastasis in patients were 97.9% (46/47) and 81.2% (9/11), respectively. Based on the number of regional lymph nodes, the specificity and sensitivity of 68Ga-PSMA PET /CT for regional lymph node diagnosis were 99.4%(326/328) and 75.0%(15/20), respectively. The specificity of lymph node metastasis in the external iliac group, the internal iliac group and the obturator group were 100.0%(114/114), 99.1%(110/111) and 98.1%(101/103), and the sensitivity was 100.0%(2/2), 60.00%(3/5) and 69.2%(9/13), respectively. Conclusion:68Ga-PSMA PET/CT can be used as a strong tool for precise guidance of PLND in PCa patients.

Objective To test and evaluate the JAK2 gene V617F mutation in patients with myeloproliferative tumors based on i-densy IS-5320 platform according to ISO15189 accreditation requirements.Methods Instrument performance verification.Selected from December 2014 to February 2017, 20 cases of JAK2 V617F mutation positive peripheral blood samples from Huashan Hospital of the Shanghai FuDan University Medical College and 20 cases of peripheral blood samples with negative JAK2V617F mutation.The Realtime PCR with TaqMan MGB probe was selected as the control method to verify and evaluate the accuracy of testing JAK 2 V617F mutation on i-densy IS-5320 platform.Whole blood samples were used to evaluate the reproducibility , cross-contamination and anti-interference ability of this platform.The ability of mutation load was verified by detecting mixtures of human erythnoleukemia cells and colorectal cancer cell HCT116 with 12 different proportions.Results I-densy IS-5320 platform and TaqMan MGB probe real-time fluorescence quantitative PCR show the same result .The within-run reproducibility and between-run reproducibility are both 100%.There is no observed contamination .High bilirubin and high triglyceride blood samples have no obvious interference on mutation detection .The mutation ratio with a load as low as 0.25%could be tested stably by i-densy IS-5320 platform.The detecting peak of melting curve can reflect the ratio of JAK2 V617F mutation to some extent.Conclusions I-densy IS-5320 can detect the mutation of JAK2 V617F gene in the whole blood directly.It has high sensitivity, accuracy and stability, and is easy to operate, and also can reflect the mutation load of JAK2 V617F, which could meet the clinical requirements for the detection of mutations.

ABSTRACT:Hypertension,the first risk factor for stroke and coronary heart disease in the Chinese population, seriously endangers people’s health.At present,China has more than 270 million people with hypertension and an annual increase rate of 1 0 million people.Then how to improve prevention and treatment of hypertension has become an urgent need to solve major medical and social problems.In the past,research on hypertension mainly focused on the peripheral area,while recent research has shown that the central regulation plays an important role in the development of hypertension. Hypothalamic paraventricular nucleus (PVN ), which plays a key role in maintaining cardiovascular activity, can directly control the sympathetic preganglionic neurons and regulate peripheral sympathetic nerve activity,thus being closely related to the development of hypertension.Research in recent years shows that the comprehensive effects of proinflammatory cytokines (PIC ),reactive oxygen species (ROS),renin-angiotensin system (RAS),neurotransmitter (NT)and nuclear factorκB (NF-κB)are involved in the pathogenesis of hypertension.However,it is unclear how these neurohormones in PVN are activated,how they interact with each other and what role they play in the regulatory mechanism of hypertension.Therefore,the key focus of this research is to explore the impact of activated neurohormones in PVN on hypertension.This study will provide new content for the study on hypertension.

Heart failure is a complex clinical syndrome,and impaired filling or ejection disorders result from any ventricular structure or dysfunction can cause heart failure.The prevalence of heart failure in adult populations in developed countries has reached 1% to 2%,while the prevalence in elderly people over 70 years of age has increased to ≥ 10%. With the population aging and the prevalence of coronary heart disease increased, the prevalence of heart failure has increased,becoming a disable and fatal disease.The changes of the central nervous system hormones such as renin-angiotensin system (RAS),inflammatory cytokines (proinflammatory cytokines,PIC),and reactive oxygen species (ROS)may be closely related to increased central activity in heart failure,which can significantly alter the activities of peripheral sympathetic nerves. Constant sympathetic nervous activity is an important cause of development of heart failure,so reducing the sympathetic excitability of heart failure is regarded as one of the focuses of treatment and research.This paper focuses on the influence of central neurohormone on heart failure and possible central mechanism.

AIM: To observe the expression of corticotropin releasing hormone (CRH) within the paraventricular nucleus of hypothalamus (PVN) and to explore the relationship between the activated CRH-containing neurons and sympathetic activity in rats with heart failure (HF).METHODS: Healthy male Sprague-Dawley (SD) rats were subjected to coronary artery ligation to induce HF, and chronic intracerebroventricular (ICV) infusion was performed by osmotic pump for 4 weeks.The rats in sham group and HF group were given vehicle (VEH;artificial cerebrospinal fluid 0.25 μL/h).The rats in HF plus treatment group were treated with CRH competitive inhibitor αh-CRH (15 mg/h).Meanwhile, the Lewis rats and Fischer 344 rats for control study also underwent coronary ligation to induce HF or sham surgery.After 4 weeks, left ventricular end-diastolic pressure (LVEDP) and maximum positive/negative change in pressure over time (±dp/dtmax) were determined.The right ventricular-to-body weight (RV/BW) and lung-to-body weight (lung/BW) ratios were calculated.The renal sympathetic nerve activity (RSNA) was recorded and the plasma norepinephrine (NE) level was measured.The expression of CRH in the PVN combined with the plasma adrenocorticotrophic hormone (ACTH) levels were measured.RESULTS: Compared with the sham-SD rats, the HF-SD rats had a greater number of CRH positive neurons in the PVN (accordingly the plasma ACTH levels were increased), accompanied by decreased ±dp/dtmax and increased RSNA, plasma NE, LVEDP, lung/BW and RV/BW.However, ICV treatment with αh-CRH attenuated these changes in the HF-SD rats (P<0.05).Compared with the sham-Fisher 344 rats, the HF-Fisher 344 rats also had a greater number of CRH positive neurons in the PVN (accordingly the plasma ACTH levels were increased).In addition, they had significantly increased RSNA and plasma NE level, higher LVEDP, RV/BW and lung/BW, and lower ±dp/dtmax (P<0.05).Compared with the SHAM-Lewis rats, the HF-Lewis rats had not significantly changed in the above parameters.CONCLUSION: In CHF, the CRH-containing neurons in PVN are activated, thus aggravating cardiac function by increasing sympathoexcitation.