BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

OBJECTIVES: Cardiovascular disease (CVD) poses a major threat to global health. Evaluating atherosclerosis in asymptomatic individuals can help identify those at high risk of CVD. This study aims to establish an individualized nomogram prediction model to estimate the risk of vascular plaque formation in asymptomatic individuals. METHODS: A total of 5 655 participants who underwent CVD screening at the Health Management Center of The Third Xiangya Hospital, Central South University, between January 2022 and June 2024 we retrospectively enrolled. Using simple random sampling, participants were divided into a training set (n=4 524) and a validation set (n=1 131) in an 8꞉2 ratio. Demographic and clinical data were collected and compared between groups. Multivariate logistic regression analysis was used to identify independent factors associated with vascular plaques and to construct a nomogram prediction model. The predictive performance and clinical utility of the model were evaluated using receiver operating characteristic (ROC) curves, the Hosmer-Lemeshow goodness-of-fit test, calibration plots, and decision curve analysis (DCA). RESULTS: The mean age of participants was 52 years old. There were 3 400 males (60.12%). The overall detection rate of vascular plaque in the screening population was 49.87% (2 820/5 655). No statistically significant differences were observed in clinical indicators between the training and validation sets (all P>0.05). Multivariate Logistic regression analysis identified age, systolic blood pressure, high-density lipoprotein (HDL), low-density lipoprotein (LDL), lipoprotein(a), male sex, smoking history, hypertension history, and diabetes history as independent risk factors for vascular plaque in asymptomatic individuals (all P<0.05). The area under the curve (AUC) of the nomogram model for predicting vascular plaque risk were 0.778 (95% CI 0.765 to 0.791, P<0.001) in the training set and 0.760 (95% CI 0.732 to 0.787, P<0.001) in the validation set. The Hosmer-Lemeshow goodness-of-fit test indicated good model calibration (training set: P=0.628; validation set: P=0.561). The calibration curve plotted using the Bootstrap method demonstrated good agreement between predicted probabilities and actual probabilities. DCA showed that the nomogram provided a clinical net benefit for predicting vascular plaque risk when the threshold probability ranged from 0.02 to 0.99. CONCLUSIONS The nomogram prediction model for vascular plaque risk, constructed using readily available and cost-effective physical examination indicators, exhibited good predictive performance. This model can assist in the early identification and intervention of asymptomatic individuals at high risk for cardiovascular disease.
Humans ; Male ; Middle Aged ; Female ; Nomograms ; Retrospective Studies ; Risk Factors ; Plaque, Atherosclerotic/diagnosis* ; Aged ; Adult ; Physical Examination ; Logistic Models ; Cardiovascular Diseases/epidemiology* ; ROC Curve

The bone formation promoter recombinant human parathyroid hormone 1-34 [PTH (1-34)] has a short half-life and low bioavailability. In this study, we prepared a biodegradable and temperature-sensitive hyaluronic acid-poly-N-isopropyl acrylamide (AHA-g-PNIPAAm), and further investigated its effects of PTH (1-34) release and cell behavior as drug carrier. The structure of AHA-g-PNIPAAM was confirmed by hydrogen nuclear magnetic resonance spectroscopy and infrared spectroscopy. Next, PTH (1-34) loaded thermo-sensitive hydrogels were prepared by physical swelling method and their stability was investigated. The morphology of hydrogel was observed by scanning electron microscope. The minimum critical transition temperature and drug release behavior of hydrogels were investigated by ultraviolet spectrophotometry. The tetrazolium-based colorimetric assay (MTT assay) was used to investigate the toxicity and proliferation effects of PTH (1-34)-loaded thermo-sensitive hydrogel on mouse mononuclear macrophage RAW264.7 and mouse precranial osteoblasts MC3T3-E1. The effect of PTH (1-34)-loaded thermo-sensitive hydrogel on the differentiation of RAW264.7 was investigated by the tartrate-resistant acid phosphatase assay. The results showed that the PTH (1-34)-loaded thermo-sensitive hydrogel prepared in this study displayed regular three-dimensional honeycomb structure, and had good stability, thermo-sensitivity and sustained and controlled release properties, which could promote the proliferation of MC3T3-E1 cells more effectively and inhibit the differentiation of RAW264.7 into osteoclasts.

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.

In this study, the lipid membrane-wrapped nanoparticles loaded with metformin polymer (PolyMet) and doxorubicin (DOX) was prepared and then evaluated therapeutic effect on breast cancer. An anionic chain PGA-DOX based on γ-polyglutamic acid (PGA) with DOX was synthesized via amidation reaction and characterized by ¹H NMR. The PGA-DOX and PolyMet were loaded via electrostatic attraction to prepare the co-delivery nanoparticles system (PolyMet-DOX-NPs). Then, PolyMet-DOX-NPs were coated with cationic liposome membrane to form the core-membrane structural system (PolyMet-DOX-lipid-nanoparticles, PolyMet-DOX-LNPs). The structure and morphology of PolyMet-DOX-LNPs were observed by transmission electron microscope. The particle size, zeta potential, encapsulation efficiency (EE), drug loading (DL), release behavior in vitro of PolyMet-DOX-LNPs were investigated. The MTT assay was used to examine the cytotoxicity of PolyMet combined with DOX on 4T-1 cells. The 4T1^Fluc tumor-bearing mice model was used to evaluate the therapeutic efficacy of PolyMet-DOX-LNPs in vivo. All animal experiments were performed in line with ethical standards and approved by the Animal Experiments Ethical Committee of Zhejiang Chinese Medical University. ¹H NMR spectrum showed that PGA-DOX was successfully synthesized with DOX grafting rate of (72.03 ± 1.29) %. The EE and DL of PolyMet-DOX-LNPs was (72.76 ± 1.92) % and (1.16 ± 0.12) %, respectively. PolyMet-DOX-LNPs exhibited a suitable size of (159.3 ± 7.4) nm and positive charge of (+36.3 ± 1.9) mV with good spheroidal morphology and dispersibility. The release profiles in vitro showed that PolyMet-DOX-LNPs exhibited a slowly and maintained release behavior at physiological pH value (pH 7.4) within 48 h. Further studies showed that PolyMet combined with DOX could synergistically enhance the cytotoxicity on 4T-1 cells. Bioluminescence imaging (BLI) result showed that the luminescence signal intensity of 4T-1^Fluc cells was reduced after treatment with PolyMet-DOX-LNPs and the tumor volume growth was also inhibited. Additionally, the H&E staining and changes of body weight showed that PolyMet could reduce the toxicity of DOX. To sum up, PolyMet has a good synergistic effect with DOX in the treatment of breast cancer, which provide the foundation for this novel metformin polymer on the anti-tumor application.

Clinical data of 12 patients with gastric cancer, in whom the Roux and Y space hernia developed after gastrectomy with Roux-en-Y anastomosis in our hospital from June 2010 to December 2018, were retrospectively analyzed. The clinical symptoms of patients were abdominal pain, distension and ileus. The main CT findings were torsion of mesentery with whirlpool sign, intestinal obstruction and exudants around the small bowels. During the operation it was found that small bowels herniated into the Roux and Y space in all 12 patients, the necrotic small intestines were resected in 4 patients. Ten patients were recovered, and 2 died. No recurrence was observed in all 10 patients during 3 month-follow up. The postoperative Roux and Y space hernia is a internal hernia and difficult to be diagnosed. The CT scan is valuable for diagnosis of Roux and Y space hernia; the main CT signs were swirled appearance of mesentery and small bowel obstruction. Once diagnosis is made the emergency operation is necessary.

Toll-like receptors (TLRs) can be recognized and activated by different pathogen associated molecular patterns (PAMPs), which induce innate immune response and inflammation of the body. Na/H exchangers (NHEs) not only play roles in the regulation of cellular pH and cell volume, maintenance of the cavity microenvironment and nutrients absorption, but also are related to cell proliferation, migration and apoptosis. The activity and membrane protein expression of NHEs are inhibited under the inflammation condition. It has been shown that the activation of TLR2 in colon epithelial cells can inhibit the activity of NHE1 through MyD88 independent pathway, which involves the recruitment of Src and the phosphorylation of PI3Ks. Other studies on intestinal macrophage showed long-term LPS stimulation can induce TLR4 activation through MyD88-dependent pathway (TLR4/MyD88/NF-κB) and induce inflammation and degeneration of intracellular NHE1, which leads to NHE1 activity inhibition. But short-term LPS exposure increases the activity and protein expression of NHE1. The activation of TLR5 increases the activity of NHE3. The activity and/or expression of NHE3 in intestinal macrophages in colitis patients and model animals were decreased. In renal tubular epithelial cells, basolateral LPS stimulation inhibits luminal NHE3 activation through TLR4/MyD88-dependent MAPK/ERK signaling pathway. And LPS stimulation on the lumen side activates TLR4/MyD88-dependent PI3K-AKT-mTOR signaling pathway, which results in the inhibition of NHE1 activity in basolateral side, and then affects the NHE3 function of the lumen side.

Background and objective Treatment options for patients with squamous cell carcinoma of the lung (SCC) are limited in chemotherapy. However, not all patients could benefit form standard platinum regimen. Considering the dismal prognosis of patients with advanced SCC, a greater focus on selecting sensitive chemotherapy regimens remains of up-most importance to improve outcomes in this disease. In this study, we used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to detect pre-chemotherapy serum peptides in advanced lung squamous cell carcinoma patients accepting paclitaxel combined with platinum chemotherapy and to analyze the correlation between serum peptides and che-motherapy efcacy. Methods Patients with advanced lung squamous cell carcinoma received paclitaxel combining with plati-num chemotherapy and evaluated the efcacy every two cycles. Evaluation of complete response (CR) or partial response (PR) patients defined as sensitive group, progressive disease (PD) patients defined as resistant group. Serum samples were collected from patients with lung squamous cell carcinoma. Eighty-one patients were randomly divided into training group (sensitive group Ⅰ and resistant group Ⅰ) and validation group (sensitive group Ⅱ and resistant group Ⅱ) according to the ratio of 3:1. Se-rum samples were pretreated and Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was used to detect serum peptide fingerprints. ClinProTools software was used to analyze the differences between the sensitive group Ⅰ and the resistant group Ⅰ. Three kinds of biological algorithms (SNN, GA, QC) built in CPT software were used to establish the curative effect prediction model respectively and the optimal algorithm was selected. The validation group was used for blind verification. Results Thirty sensitive patients and 31 resistant patients were enrolled in the training group. Ten sensitive patients and 10 resistant patients were included in the validation group. The training group had 96 differentially expressed peptides in the sensitive and resistant patients, with 16 statistically significant peptides (P<0.001). The predictive model was established by 5 polypeptides (1,897.75 Da, 2,023.93 Da, 3,683.36 Da, 4,269.56 Da, 5,341.29 Da). The recognition rate of this model was 89.18% and the cross validation rate was 95.11%. The accuracy of the model was 85%, the sensitivity was 90.0% and the specificity was 80.0%. The median PFS in the sensitive group was better than patients in the resistant group (7.2 months 95%CI: 4.4-14.5 vs 1.8 months 95%CI: 0.7-3.5). The results showed that the differential peptides 4,232.04 Da and 4,269.56 Da were correlated with PFS in patients with lung squamous cell carcinoma (P<0.001). Conclusion MALDI-TOF-MS was used to detect the difference of serum peptides between sensitive and resistant groups. The preliminary curative effect prediction model was used to predict the efcacy of paclitaxel combined with platinum regimen. However, this model need further investigations to verify the accuracy and the sensitivity.

Disorders of sex development (DSD) is defined as a congenital condition or atypical development of the chromosomal, gonadal, or anatomic sex. The diagnosis, gender assignment, and treatment of DSD require the guidance from experienced multidisciplinary teams. So far there has been no consensus about it in China. Due to dysgenetic gonads, defects in sex steroid biosynthesis or action, or gonadectomy during the prepubertal years, those with DSD suffer from hypogonadism. The hormone replacement therapy of DSD aims at general physiological health and long-term prognosis as well as the avoidance of unnecessary genital and gonadal surgery. This review focuses on the advances in the studies of the diagnosis and hormone replacement therapy of 46,XY DSD.
46, XY Disorders of Sex Development ; diagnosis ; drug therapy ; China ; Gonadal Steroid Hormones ; biosynthesis ; Gonads ; growth & development ; Hormone Replacement Therapy ; Humans ; Male ; Prognosis

ObjectiveTo investigate the efficacy of Baihe Xiaoyao powder in patients with chronic hepatitis B (CHB) and depression, and to explore its mechanism of action from the perspectives of endocrine and immune function. MethodsA total of 120 patients with CHB who visited the Outpatient Department of Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine from September 2013 to February 2015 were enrolled, and according to the Hamilton Depression Scale (HAMD) scores, they were divided into CHB-depression group (80 patients) and CHB group (40 patients). The levels of cortisol (Cor) and interleukin-2 (IL-2) and the proportion of natural killer (NK) cells were compared between the two groups. The 80 patients in the CHB-depression group were further divided into control group and treatment group, with 40 patients in each group. The patients in the control group were treated with entecavir for 12 weeks, and those in the treatment group were treated with entecavir and Baihe Xiaoyao powder for 12 weeks. The effects of Baihe Xiaoyao powder on liver function ［alanine aminotransferase (ALT) and aspartate aminotransferase (AST)］, hepatitis B virus (HBV) DNA, HAMD score, Cor, and immune function (IL-2 and NK cells) were observed in patients with CHB and depression. The t-test was used for comparison of continuous data, the chi-square test was used for categorical data, and correlation analysis was also performed. ResultsCompared with CHB patients without depression, those with depression had a significantly higher level of Cor, a significantly lower level of IL-2, and a significantly lower proportion of NK cells (P＜0.01), and Cor level was negatively correlated with IL-2 level (r=-0.786, P＜0.01) and the proportion of NK cells (r=-0.681, P＜0.01). After the treatment with Baihe Xiaoyao powder for 12 weeks, compared with the control group, the treatment group had significantly lower HAMD score and levels of Cor, ALT, and AST (P＜0.01) and significantly higher level of IL-2, proportion of NK cells, and HBV DNA clearance rate (P＜0.05). ConclusionThe CHB patients with depression have endocrine disorders, an increased serum level of Cor, a reduced level of IL-2, and a reduced proportion of NK cells. Baihe Xiaoyao powder can improve depressive emotion, reduce the level of Cor, improve the body's immune function and liver function, and increase HBV DNA clearance rate. A combination of Baihe Xiaoyao powder and antiviral therapy can improve the clinical outcome of CHB.