Objective To investigate the effect of Kaixinsan(KXS,a traditional Chinese medicine formula)for alleviating adriamycin-induced depression-like behaviors in mice bearing breast cancer xenografts and explore the pharmacological mechanism.Methods Forty female BALB/c mice were randomized equally into control group,model group,and low-and high-dose KXS treatment groups,and in the latter 3 groups,mouse models bearing orthotopic breast cancer 4T1 cell xenografts were established and treated with adriamycin along with saline or KXS via gavage.Depression-like behaviors of the mice were assessed using open field test and elevated plus-maze test,and the changes in serum levels of depression-related factors were examined.RNA-seq analysis and transmission electron microscopy were used and ferroptosis-related factors were detected to explore the mechanisms of adriamycin-induced depression and the therapeutic mechanism of KXS.The results were verified in SH-SY5Y cells using ferroptosis inhibitor Fer-1 as the positive control.Results KXS significantly alleviated depression-like behaviors and depression-related serological changes induced by adriamycin in the mouse models.RNA-seq results suggested that KXS alleviated chemotherapy-induced depression by regulating oxidative stress,lipid metabolism and iron ion binding in the prefrontal cortex.Pathological analysis and detection of ferroptosis-related factors showed that KXS significantly reduced ferroptosis in the prefrontal cortex of adriamycin-treated mice.In SH-SY5Y cells,both KXS-medicated serum and the ferroptosis inhibitor were capable of attenuating adriamycin-induced cell ferroptosis.Conclusion KXS alleviates adriamycin-induced depression-like behaviors in mice by reducing ferroptosis in the prefrontal cortex of breast cancer-bearing mice.

Objective To investigate the effect of Kaixinsan(KXS,a traditional Chinese medicine formula)for alleviating adriamycin-induced depression-like behaviors in mice bearing breast cancer xenografts and explore the pharmacological mechanism.Methods Forty female BALB/c mice were randomized equally into control group,model group,and low-and high-dose KXS treatment groups,and in the latter 3 groups,mouse models bearing orthotopic breast cancer 4T1 cell xenografts were established and treated with adriamycin along with saline or KXS via gavage.Depression-like behaviors of the mice were assessed using open field test and elevated plus-maze test,and the changes in serum levels of depression-related factors were examined.RNA-seq analysis and transmission electron microscopy were used and ferroptosis-related factors were detected to explore the mechanisms of adriamycin-induced depression and the therapeutic mechanism of KXS.The results were verified in SH-SY5Y cells using ferroptosis inhibitor Fer-1 as the positive control.Results KXS significantly alleviated depression-like behaviors and depression-related serological changes induced by adriamycin in the mouse models.RNA-seq results suggested that KXS alleviated chemotherapy-induced depression by regulating oxidative stress,lipid metabolism and iron ion binding in the prefrontal cortex.Pathological analysis and detection of ferroptosis-related factors showed that KXS significantly reduced ferroptosis in the prefrontal cortex of adriamycin-treated mice.In SH-SY5Y cells,both KXS-medicated serum and the ferroptosis inhibitor were capable of attenuating adriamycin-induced cell ferroptosis.Conclusion KXS alleviates adriamycin-induced depression-like behaviors in mice by reducing ferroptosis in the prefrontal cortex of breast cancer-bearing mice.

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Achalasia is a primary esophageal motility disorder manifested by dysphagia and chest pain that impair patients’ quality of life, and it also leads to chronic esophageal inflammation by food retention and increases the risk of esophageal cancer. Although achalasia has long been reported, the epidemiology, diagnosis and treatment of achalasia are not fully understood. The current clinical dilemma of achalasia is mainly due to its unclear pathogenesis. In this paper, epidemiology, diagnosis treatment, as well as possible pathogenesis of achalasia will be reviewed and summarized. The proposed hypothesis on the pathogenesis of achalasia is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in lower esophageal sphincter.

Objective:To investigate the feasibility and efficacy of retroperitoneal laparoscopy combined with lower abdominal incisions in the surgical treatment of upper urinary tract urothelial cell carcinoma.Methods:The clinical data of 52 patients with renal pelvic and ureteral cancer, who received radical nephrectomy using the retroperitoneal laparoscopy combined with a lower abdomen incision approach in Hubei Provincial General Hospital of Armed Police Force from April 2005 to December 2016, were retrospectively analyzed. All 52 patients had unilateral renal pelvic and ureteral cancer but with no lymph nodes or distant metastasis. During general anesthesia in a healthy side-lying position, patients underwent retroperitoneal laparoscopic radical nephrectomy. The affected ureter was clamped but not disconnected. Renal blood vessels were clamped with Hem-o-lock clips. Renal arteries and veins were cut off. Then the kidney was completely isolated. Three laparoscopic incisions were sutured. After taking the patients to be in the supine position, a 5-6 cm-long incision was made in the lower abdomen on the affected side. The lower ureter was dissociated from the bladder. A 1.5 cm-long bladder wall was dissected in the sleeve manner. The affected kidney and ureter were completely removed from the lower abdomen through the made small incision. A rubber drainage tube was inserted in another incision made at the lower end of the prior incision.Results:Operations were successful in all 52 cases. No cases were converted to open surgery, had blood transfused, or needed secondary surgery. There were no complications such as urinary leakage, incision infection, or massive bleeding. Postoperative pathology reported 41 cases of renal urothelial carcinoma and 11 cases of ureteral urothelial carcinoma. Forty-eight patients provided follow-up data, and four did not because of being lost. One patient died of a cardiovascular accident 13 months after surgery. Cystoscopy revealed that 47 cases had no bladder tumor, local or distant metastasis.Conclusion:The retroperitoneal laparoscopy combined with lower abdominal incisions approach is suitable for radical resection of renal pelvic or ureteral cancer owing to ease in operation, few requirements for surgical instruments, minimal invasion, and rapid recovery.

Objective:To investigate the characteristics and management of the emergency patients with orthopaedic trauma during COVID-19 epidemic.Methods:A retrospective analysis was performed of the 32 emergency inpatients at Department of Orthopedics, Nanfang Hospital from January 20 to February 26, 2020. They were 23 males and 9 females, aged from 4 to 66 years (mean, 35 years). The causes for their injury included traffic accident in 14 cases, sharp cutting (e.g. by a kitchen knife) in 6 cases, heavy object crushing in one, machine crushing in one, fall in 2, and machine twisting in one. High energy injury occurred in 13 cases and low-energy injury in 9 cases. The injury involved the upper limb in 7 cases and the lower limb in 15 cases. Grade Ⅱ protection was adopted during the diagnosis and treatment for the one emergency patient who had not undergone nucleic acid screening for 2019-nCoV while grade Ⅰ protection for the other 21 patients. 2019-nCoV infection was recorded in the patients and medical staff as well. The measures and experience were reviewed in the management of orthopaedic emergencies during the COVID-19 epidemic.Results:During the diagnosis and treatment of 22 emergency patients with orthopaedic trauma, none of the medical staff or patients was infected with COVID-19. As the one emergency patient was treated as a suspected case and protected by grade Ⅱ measures, COVID-19 infection was ruled out after surgery.Conclusions:During the COVID-19 epidemic, front-line medical staff dealing with traumatic emergencies faced a higher risk of infection. The emergency orthopaedic traumas were mainly caused by a traffic accident or a machine, and those in the elderly patients by a sharp cutting or a fall. The incidence of COVID-19 infection could be reduced by COVID-19 screening before admission, appropriate anesthesia and surgical methods, protection of perioperative medical staff, postoperative wards care and psychological counseling.

Objective To explore the effects of Na+ H-exchanger 1(NHE1) knockdown on ATP binding cassette transporter A1 (ABCA1) protein expression levels and cholesterol efflux in the hypoxic RAW264.7 cells.Methods The RAW264.7 cells were infected with lentiviral vectors expressing shRNA specific for NHE1(siNHE1) or scramble RNA (siNC).The expression of NHE1 at mRNA or protein level was detected by qRT-PCR and Western blotting respectively in the infected cells after 24 h in a hypoxia condition.In the meantime,the methods of SNARF-1,Fluo-4 NW andSuc-LLVY-aminoluciferin were employed to determine NHE1 activity,intracellular Ca2+ ([Ca2+]i) and calpain activity,respectively.Furthermore,ABCA1 protein levels were detected by Western blotting in the 24 h hypoxic cells.In parallel,the intracellular cholesterol content and cholesterol efflux were analyzed by the methods of combined enzymatic HLPC and 3 H-cholesterol.Results The hypoxia condition versus the normoxia condition up-regulated NHE1 mRNA and protein expression level and activity by 2.48 folds,1.28 folds and 61.96％ (all P＜0.05),and increased[Ca2+]i and calpain activity by 4.51 folds and 2.41 folds(all P＜0.05).Whereas the NHE1 mRNA and protein expression and activity at the presence of hypoxia were inhibited by siNHE1 with the inhibition ratio of 84.95％,60.75％ and 66.44％,respectively (all P＜0.05)and[Ca2+]i and calpain activity were reduced by 59.23％ and 54.66％ (P＜0.05).Furthermore,the ABCA1 protein level was 61.67％ lower in the hypoxic cells than in the normoxic cells (P＜0.05),and siNHE1 was increased by 56.52％ after treatment of Hypoxia.Hypoxia elevated intracellular total cholesterol and cholesterol ester by 74.57 ％ and 101.81％ (all P＜0.05).Treatment with siNHE1 in the hypoxia condition can reduce total cholesterol and cholesterol ester by 34.24 ％ 及 49.66 ％ (all P＜0.05).Hypoxia reduced the cholesterol efflux by 34.79％(P＜0.05),which were partially reversed by siNHE1.Conclusions NHE1 might play an important role in hypoxia-induced ABCA1 protein attenuation and reverse cholesterol transport dysfunction through[Ca2+]i/calpain pathway.

OBJECTIVETo identify the value of lymphography in the location and treatment decision of chyle leakage.

METHODSThe clinic data of 177 patients suffered from chyle leakage admitted in 6 medical centers in Shanghai from February 1998 to December 2014 was analyzed retrospectively. There were 94 male and 83 female patients aging from 9 to 84 years with a mean of 49 years, including 128 cases of chyluria, 34 cases of primary chylothorax and 15 cases of other chyle leakage. All patients had failed to conservative treatment more than 2 weeks. Pedal lymphography was performed in every patient to investigate the site and range of chyle leakage. Effect of surgical or conservative management was compared according to the different results of lymphography.

RESULTSNo serious complication was noticed. For all 177 patients, lymphography showed localized lymphatic diseases in 148 cases (83.6%), including 125 cases of lymphatic renal pelvic leaks, 14 cases of unilateral identified leak within thorax and 9 cases of chyle leakage in neck, heart, abdomen or scrotum. Among these patients, surgical treatment cured 129 and improved 3 patients but failed in 2 patients, while the remaining 14 cases had their leaks decreased after lymphography and cured by conservative management. For those 15 patients having disseminated lymphatic diseases or 14 with no abnormality under lymphography, surgery only cured 2 and improved 1 patient but failed in 8 patients (with 3 death), whereas continuous conservative treatment cured 11 patients, improved 5 patients but only failed in 2 patients (with one death). For localized leakage, surgical treatment showed better efficacy (98.5% vs. 3/11), whereas conservative treatment had significantly higher successful rate than surgical interventions in patients with disseminated lymphatic diseases or no abnormality under lymphography (16/18 vs. 3/11).

CONCLUSIONSLymphography could identify the location and range of complicate chyle leakage failed to primary conservative management. Patients with disseminated lymphatic diseases or no abnormality under lymphography would be better managed by continuous non-operative treatment partly due to therapeutic effect of lymphography, while surgical intervention could be a good option for patients having localized lymphatic etiology.

Abdominal Cavity ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Chyle ; Chylothorax ; diagnosis ; surgery ; Female ; Heart ; Humans ; Kidney Pelvis ; Lymphatic Diseases ; Lymphography ; Male ; Middle Aged ; Neck ; Retrospective Studies ; Scrotum ; Young Adult

ObjectiveTo investigate the clinical effect of entecavir (ETV) combined with Fuzheng Huayu capsules in the treatment of patients with compensated chronic hepatitis B-related cirrhosis. MethodsA total of 142 patients with compensated chronic hepatitis B-related cirrhosis who visited the Sixth People′s Hospital Qingdao from January 2013 to December 2015 were randomly divided into treatment group and control group, with 71 patients in each group. Both groups were given conventional treatment such as liver-protecting and symptomatic treatment. The patients in the control group were given ETV 0.5 mg/day, while those in the treatment group received oral administration of Fuzheng Huayu capsules 1.5 g twice a day in addition to the treatment in the control group. Both groups were treated for 12 months. The changes in inflammatory factors and fibrosis markers were observed. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. ResultsAfter the 12-month treatment, the treatment group and the control group showed no significant difference in the serum HBV DNA clearance rate ［91.5% (65/71) vs 90.1% (64/71), P=0.771］. Compared with the control group, the treatment group showed significant reductions in serum hyaluronic acid, laminin, procollagen type III, collagen type IV, alanine aminotransferase, aspartate aminotransferase, liver stiffness measurement, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and hypersensitive C-reactive protein (hs-CRP) (t=16187，5343，13697，17121，7409，27371，7973，5471，7885，9057，8171，all P＜0.001). ConclusionCompared with ETV alone, ETV combined with Fuzheng Huayu capsules exerts a better anti-fibrotic effect and can inhibit the release of TNF-α, IL-6, IL-8 and hs-CRP in patients with compensated chronic hepatitis B-related cirrhosis.

Objective To investigate the effect of citric acid and ambroxol on clearing insoluble particles of depleted uranium in rat lungs by establishing a tracheal perfusion model.Methods One hundred and fifty male Wistar rats were randomly divided into model exposure group, normal control group(NC group), depleted uranium exposure group(DU), citric acid treatment group( CA) , ambroxol treatment group( AM) and citric acid+ambroxol treatment group( CA+AM) . The rats were sacrificed on 7, 15 and 30 days.Uranium content in the lungs was detected by microwave digestion method, pathological changes in the lungs were observed, and inflammatory factors of lung homogenates were detected.Results Compared to DU control group, the intrapulmonary uranium deposit amount in experimental groups was significantly reduced on 7 and 15 days (P<0.05).HE stained lung tissue showed that the pathological changes in treatment groups were less significant than in DU control group.The level of IL-1α,IL-1β,and IL-2 was significantly lower than in DU control, but the level of MCP-1 and MIP-1 was observably higher.Conclusion Citric acid and ambroxol can evidently improve the clear-ance of lung uranium and reduce damnification of lung tissues.Drug treatment can reduce the level of pulmonary inflamma-tory cytokines alleviate the chronic inflammation in the lungs, and enhance the capacity of macrophage to recruitment.