Background: Twenty-four-hour urinary free cortisol (UFC) measurement is the initial diagnostic test for Cushing’s syndrome (CS). We compared UFC determination by both direct and extraction immunoassays using Abbott Architect, Siemens Atellica Solution, and Beckman DxI800 with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, we evaluated the value of 24-hr UFC measured by six methods for diagnosing CS. Methods: Residual 24-hr urine samples of 94 CS and 246 non-CS patients were collected.A laboratory-developed LC-MS/MS method was used as reference. UFC was measured by direct assays (D) using Abbott, Siemens, and Beckman platforms and by extraction assays (E) using Siemens and Beckman platforms. Method was compared using Passing–Bablok regression and Bland–Altman plot analyses. Cut-off values for the six assays and corresponding sensitivities and specificities were calculated by ROC analysis. Results: Abbott-D, Beckman-E, Siemens-E, and Siemens-D showed strong correlations with LC-MS/MS (Spearman coefficient r = 0.965, 0.922, 0.922, and 0.897, respectively), while Beckman-D showed weaker correlation (r = 0.755). All immunoassays showed proportionally positive bias. The areas under the curve were 0.975 for Abbott-D, 0.972 for LCMS/MS, 0.966 for Siemens-E, 0.948 for Siemens-D, 0.955 for Beckman-E, and 0.877 for Beckman-D. The cut-off values varied significantly (154.8–1,321.5 nmol/24 hrs). Assay sensitivity and specificity ranged from 76.1% to 93.2% and from 93.0% to 97.1%, respectively. Conclusions Commercially available immunoassays for measuring UFC show different levels of analytical consistency compared to LC-MS/MS. Abbott-D, Siemens-E, and Beckman-E have high diagnostic accuracy for CS.

Objective To explore the mechanism of Angelica Sinensis polysaccharide(ASP)promoting donor bone marrow transplantation(BMT)to reconstruct hematopoietic function of receptor mice by regulating bone marrow stromalcells(BMSCs).Methods Bone marrow mononuclear cells(BMMNCs)of male C57BL/6J mice aged 8-10 weeks were separated,purified and transplanted into female receptor mice of the same age.On the ninth day,receptor mice BMMNCs were separated,purified and transplanted again into female receptor mice.The transplanted receptor mice were divided into control group:sham irradiation;Irradiation(IR)group:a whole-body irradiation with a total dose of 8.0 Gy X-ray;BMT group:the receptor mice treated in the same way as the IR group and transplanted BMMNCs(5×106 cells)from male donor via the tail vein;BMT+ASP group:the receptor mice treated in the same way as the BMT group,and injected ASP[100 mg/(kg·d)×9]by intraperitoneal route from the first day of transplantation.Changes in body weight and survival rate of mice were recorded during modeling,receptor mice BMMNCs were collected to detect sex-determining region of Y(SRY)gene after building model,peripheral blood indexes,the number of BMMNCs in femur and histopathology of bone marrow were detected;BMSCs in receptor mice was separated and purified,BMSCs adhesion ability was observed,proliferation ability was detected by 5-ethynyl-2-deoxyuridine(EdU);The level of reactive oxygen species(ROS),the activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in BMSCs were detected;The levels of granulocyte-macrophage colony-stimulating factor(GM-CSF),stem cell factor(SCF),insulin-like growth factor 1(IGF-1)in culture supernatant of BMSCs were determined,CFU-Mix was counted after BMMNCs co-cultured with receptor BMSCs in each group for 48 hours;The expression of Notch signaling pathway related genes(Notch1,Jagged1,Hes1)in BMMNCs were measured by Real-time PCR.Results All mice in IR group were died,the body weight loss in BMT+ASP group was not obvious.The SRY gene was detected in the receptor female mice BMMNCs.Peripheral blood indexes and the number of BMMNCs were not significantly decreased in BMT+ASP group receptor mice,and bone marrow histopathological injury was reduced.ASP promoted the proliferation of BMSCs,decreased the contents of ROS and MDA,and increased the activity of SOD in BMSCs.ASP promoted the secretion of SCF,GM-CSF and IGF-1 in BMSCs,and increased CFU-Mix yield of BMMNCs co-cultured with receptor BMSCs.ASP increased the expression of Notch1,Jagged1 and Hes1 mRNA in BMMNCs.Conclusion The mechanism of ASP promoting receptor hematopoietic function reconstruction is related to reducing the oxidative stress damage of hematopoietic microenvironment,improving the secretion of hematopoietic growth factors in BMSCs,and regulating Notch signaling pathway.

Objective:To compare the diagnostic efficacy of 22 G fine needle aspiration (FNA) needles and 22 G end-cutting fine needle biopsy (FNB) needles for solid pancreatic lesion using both cytological and histological examination.Methods:Clinical data of 116 patients who underwent endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNA/FNB) at the Digestive Endoscopy Center of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from June 2022 to March 2023 were retrospectively analyzed. Sixty-three patients sampled with 22 G FNA needles were the FNA group, and 53 sampled with 22 G FNB needles were the FNB group. The diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and cytological and histological diagnostic yield of FNA needles and FNB needles for solid pancreatic lesions were compared.Results:There were no significant differences in age, gender, lesion location, lesion size, or the number of passes between the FNA group and the FNB group ( P>0.05). There were no significant differences in the diagnostic accuracy [93.7% (59/63) VS 90.6% (48/53), P=0.730], sensitivity [93.0% (53/57) VS 90.2% (46/51), P=0.732], specificity [100.0% (6/6) VS 100.0% (2/2), P=1.000], positive predictive value [100.0% (53/53) VS 100.0% (46/46), P=1.000] and negative predictive value [60.0% (6/10) VS 28.6% (2/7), P=0.335] of combined cytology and histology in distinguishing benign and malignant lesions between the two groups. In the FNA group, the diagnostic accuracy of combined cytology and histology was higher than cytology alone [93.7% (59/63) VS 81.0% (51/63), P=0.008], and was higher than histology alone without statistical significance [93.7% (59/63) VS 87.3% (55/63), P=0.125]. In the FNB group, the diagnostic accuracy of combined cytology and histology was higher than cytology alone [90.6% (48/53) VS 69.8% (37/53), P=0.001], but not than histology alone [90.6% (48/53) VS 90.6% (48/53)， P=1.000]. For solid masses located in pancreatic body/tail, the diagnostic accuracy for malignancy by histology using FNB needles tended to be higher than that of FNA needles [100.0% (17/17) VS 81.3% (26/32), P=0.080]. Conclusion:Both FNA needles and FNB needles exhibit adequate diagnostic yield for solid pancreatic masses when combining cytology and histology. FNB needles may offer a higher histological diagnostic yield.

INTRODUCTION: Despite the challenges related to His bundle pacing (HBP), recent data suggest an improved success rate with experience. As a non-university, non-electrophysiology specialised centre in Singapore, we report our experiences in HBP using pacing system analyser alone. METHODS: Data of 28 consecutive patients who underwent HBP from August 2018 to February 2019 was retrospectively obtained. The clinical and technical outcomes of these patients were compared between two timeframes of three months each. Patients were followed up for 12 months. RESULTS: Immediate technical success was achieved in 21 (75.0%) patients (mean age 73.3 ± 10.7 years, 47.6% female). The mean left ventricular ejection fraction was 53.9% ± 12.1%. The indications for HBP were atrioventricular block (n = 13, 61.9%), sinus node dysfunction (n = 7, 33.3%) and upgrade from implantable cardioverter-defibrillator to His-cardiac resynchronisation therapy (n = 1, 4.8%). No significant difference was observed in baseline characteristics between Timeframe 1 and Timeframe 2. Improvements pertaining to mean fluoroscopy time were achieved between the two timeframes. There was one HBP-related complication of lead displacement during Timeframe 1. All patients with successful HBP achieved non-selective His bundle (NSHB) capture, whereas only eight patients had selective His bundle (SHB) capture. NSHB and SHB capture thresholds remained stable at the 12-month follow-up. CONCLUSION Permanent HBP is feasible and safe, even without the use of an electrophysiology recording system. This was successfully achieved in 75% of patients, with no adverse clinical outcomes during the follow-up period.
Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Male ; Bundle of His ; Follow-Up Studies ; Stroke Volume ; Retrospective Studies ; Treatment Outcome ; Cardiac Pacing, Artificial/adverse effects* ; Electrocardiography ; Ventricular Function, Left/physiology*

Objective To investigate the titer stability of the harvest solution of severe acute respiratory syndrome coronavirus2(SARS-CoV-2)at 2 ～ 8 ℃ and the inactivation effect of β-propiolactone inactivator on the virus.Methods Three batches of SARS-CoV-2 harvest solution(batch numbers:202111001,202111002 and 202111003)were stored at 2 ～ 8 ℃ for 12 d and sampled every 3 d(0,3,6,9 and 12 d)for detection of the titers by Karber method;Three batches of virus harvest solution equilibrated overnight at 2 ～ 8 ℃ were inactivated by adding β-propiolactone at a volume fraction of 1∶4 000 and detected for the titers at different inactivation time points(0,0.5,1,1.5,2,3,4,8,16 and 24 h),of which samples inactivated for 8,16 and 24 h were taken for inactivation verification,and samples inactivated for 24 h were observed by transmission electron microscope.Results The titers of SARS-CoV-2 decreased with the prolongation of storage time at 2 ～8 ℃,which showed no obvious decrease during 0 ～ 3 d,while decreased from the initial 7.75,6 and 7.5 lgCCID_(50)/mL to5.75,4.625 and 6.25 lgCCID_(50)/mL on day 12,indicating that the virus activity showed a gradual decrease trend at 2 ～8 ℃；With the inactivation time,the virus titer decreased continuously and could not be detected after inactivation for 3 h.Transmission electron microscope observation showed that the inactivated virus particles were intact and the spike protein was evenly distributed.Conclusion The virulence of SARS-CoV-2 stored at 2 ～ 8 ℃ was unstable,so the subsequent inactivation and purification process should be carried out as soon as possible;The titer of virus could not be detected after3 h of inactivation,which provided a reference for the determination of the inactivation process.

Glycogen synthase kinase-3β (GSK-3β) is an important serine/threonine kinase that implicates in multiple cellular processes and links with the neurodegenerative diseases including Alzheimer’s disease (AD). In this study, structure-based virtual screening was performed to search database for compounds targeting GSK-3β from Enamine’s screening collection. Of the top-ranked compounds, 7 primary hits underwent a luminescent kinase assay and a cell assay using human neuroblastoma SH-SY5Y cells expressing Tau repeat domain (TauRD) with pro-aggregant mutation ΔK280. In the kinase assay for these 7 compounds, residual GSK-3β activities ranged from 36.1% to 90.0% were detected at the IC50 of SB-216763. In the cell assay, only compounds VB-030 and VB-037 reduced Tau aggregation in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. In SH-SY5Y cells expressing ΔK280 TauRD, neither VB-030 nor VB-037 increased expression of GSK-3α Ser21 or GSK-3β Ser9. Among extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT), mitogen-activated protein kinase 14 (P38) and mitogenactivated protein kinase 8 (JNK) which modulate Tau phosphorylation, VB-037 attenuated active phosphorylation of P38 Thr180/ Tyr182, whereas VB-030 had no effect on the phosphorylation status of ERK, AKT, P38 or JNK. However, both VB-030 and VB-037 reduced endogenous Tau phosphorylation at Ser202, Thr231, Ser396 and Ser404 in neuronally differentiated SH-SY5Y expressing ΔK280 TauRD. In addition, VB-030 and VB-037 further improved neuronal survival and/or neurite length and branch in mouse hippocampal primary culture under Tau cytotoxicity. Overall, through inhibiting GSK-3β kinase activity and/or p-P38 (Thr180/Tyr182), both compounds may serve as promising candidates to reduce Tau aggregation/cytotoxicity for AD treatment.

OBJECTIVE: To observe the effects of moxibustion on the stem cell factor (SCF)/tyrosine kinase receptor (c-kit) signaling pathway and immune function in rats with diarrhea irritable bowel syndrome (IBS-D), and to explore the mechanism of moxibustion for IBS-D. METHODS: Among 52 young rats born from 6 healthy pregnant SPF rats, 12 rats were randomly selected into the normal group, and the remaining 40 rats were treated with the three-factor combination method of maternal separation, acetic acid enema and chronic restraint stress to establish the IBS-D rat model. Thirty-six rats with successful IBS-D model were randomly divided into a model group, a moxibustion group, and a medication group, 12 rats in each group. The rats in the moxibustion group were treated with suspension moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37); the rats in the medication group were treated with intragastric administration of rifaximin suspension (150 mg/kg). All the treatments were given once a day for 7 consecutive days. The body mass, loose stool rate (LSR), the minimum volume threshold when abdominal withdrawal reflex (AWR) scored 3 were measured before acetic acid enema (35 days old), after modeling (45 days old), and after intervention (53 days old). After intervention (53 days old), HE staining was used to observe the morphology of colon tissue, and spleen and thymus coefficients were measured; ELISA method was used to detect serum inflammatory factors (tumor necrosis factor a [TNF-a], interleukin [IL]-10, IL-8), T-lymphocyte subsets (CD⁺₄, CD⁺₈, CD⁺₄₅), value of CD⁺₄/CD⁺₈ and immune globulin (IgA, IgG, IgM); real-time PCR method and Western blot method was used to detect the expression of SCF, c-kit mRNA and protein in colon tissue; immunofluorescence staining method were used to detect positive expression of SCF and c-kit. RESULTS: After intervention, compared with the normal group, in the model group, the body mass and the minimum volume threshold when AWR scored 3 were decreased (P<0.01), LSR, spleen and thymus coefficients, serum levels of TNF-α, IL-8, CD⁺₄, CD⁺₄₅, CD⁺₄/CD⁺₈, IgA, IgG, IgM were increased (P<0.01), serum IL-10 level and protein and mRNA expression of SCF and c-kit in colon tissue were decreased (P<0.01), and the positive expression of SCF and c-kit was decreased (P<0.01). Compared with the model group, in the moxibustion group and the medication group, the body mass and the minimum volume threshold when AWR scored 3 were increased (P<0.01, P<0.05), LSR, spleen and thymus coefficients, serum levels of TNF-α, IL-8, CD⁺₄, CD⁺₈, CD⁺₄₅, CD⁺₄/CD⁺₈, IgA, IgG, IgM were decreased (P<0.01, P<0.05), serum IL-10 level and protein and mRNA expression of SCF and c-kit in colon tissue were increased (P<0.01), and the positive expression of SCF and c-kit was increased (P<0.01). Compared with the medication group, in the moxibustion group, the level of serum CD⁺₄ was decreased (P<0.05), the value of CD⁺₄/CD⁺₈ was increased (P<0.01), and there was no significant difference in other indexes (P>0.05). The expression of SCF and c-kit mRNA was positively correlated with the minimum volume threshold when AWR scored 3 and IL-10 (P<0.01), and negatively correlated with remaining indexes (P<0.01, P<0.05). CONCLUSION Moxibustion could reduce visceral hypersensitivity, improve symptoms of abdominal pain and diarrhea in IBS-D rats, and its mechanism may be related to up-regulation of the expression of SCF/c-kit signaling pathway and improvement of IBS-D immune function.
Rats ; Animals ; Irritable Bowel Syndrome/therapy* ; Moxibustion/methods* ; Rats, Sprague-Dawley ; Interleukin-10 ; Interleukin-8 ; Maternal Deprivation ; Tumor Necrosis Factor-alpha ; Diarrhea ; Signal Transduction ; Homeostasis ; Receptor Protein-Tyrosine Kinases ; Immunity ; Immunoglobulin A ; Immunoglobulin M

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

OBJECTIVE: To analyze the association between exposure to second-hand smoke (SHS) and 23 diseases, categorized into four classifications, among the Chinese population. METHODS: We searched the literature up to June 30, 2021, and eligible studies were identified according to the PECOS format: Participants and Competitors (Chinese population), Exposure (SHS), Outcomes (Disease or Death), and Study design (Case-control or Cohort). RESULTS: In total, 53 studies were selected. The odds ratio (OR) for all types of cancer was 1.79 (1.56-2.05), and for individual cancers was 1.92 (1.42-2.59) for lung cancer, 1.57 (1.40-1.76) for breast cancer, 1.52 (1.12-2.05) for bladder cancer, and 1.37 (1.08-1.73) for liver cancer. The OR for circulatory system diseases was 1.92 (1.29-2.85), with a value of 2.29 (1.26-4.159) for stroke. The OR of respiratory system diseases was 1.76 (1.13-2.74), with a value of 1.82 (1.07-3.11) for childhood asthma. The original ORs were also shown for other diseases. Subgroup analyses were performed for lung and breast cancer. The ORs varied according to time period and were significant during exposure in the household; For lung cancer, the OR was significant in women. CONCLUSION The effect of SHS exposure in China was similar to that in Western countries, but its definition and characterization require further clarification. Studies on the association between SHS exposure and certain diseases with high incidence rates are insufficient.
Child ; Female ; Humans ; Asthma/epidemiology* ; Breast Neoplasms ; East Asian People ; Lung Neoplasms/etiology* ; Tobacco Smoke Pollution/adverse effects* ; China

OBJECTIVE: No consensus exists on the relative risk ( RR) of lung cancer (LC) attributable to active smoking in China. This study aimed to evaluate the unified RR of LC attributable to active smoking among the Chinese population. METHODS: A systematic literature search of seven databases was conducted to identify studies reporting active smoking among smokers versus nonsmokers in China. Primary articles on LC providing risk estimates with their 95% confidence intervals ( CIs) for "ever" "former" or "current" smokers from China were selected. Meta-analysis was used to estimate the pooled RR of active smoking. RESULTS: Forty-four unique studies were included. Compared with that of nonsmokers, the pooled RR (95% CI) for "ever" "former" and "current" smokers were 3.26 (2.79-3.82), 2.95 (1.71-5.08), and 5.16 (2.58-10.34) among men, 3.18 (2.78-3.63), 2.70 (2.08-3.51), and 4.27 (3.61-5.06) among women, and 2.71 (2.12-3.46), 2.66 (2.45-2.88), and 4.21 (3.25-5.45) in both sexes combined, respectively. CONCLUSION The RR of LC has remained relatively stable (range, 2-6) over the past four decades in China. Early quitting of smoking could reduce the RR to some extent; however, completely refraining from smoking is the best way to avoid its adverse effects.
Male ; Humans ; Female ; Smoking/epidemiology* ; Smoking Cessation ; Smokers ; Risk ; Lung Neoplasms/etiology* ; Risk Factors