BACKGROUND: Cancer stem-like cells (CSCs) are a small subset of cells in tumors that exhibit self-renewal and differentiation properties. CSCs play a vital role in tumor formation, progression, relapse, and therapeutic resistance. B7-H3, an immunoregulatory protein, has many protumor functions. However, little is known about the mechanism underlying the role of B7-H3 in regulating gastric cancer (GC) stemness. Our study aimed to explore the impacts of B7-H3 on GC stemness and its underlying mechanism. METHODS: GC stemness influenced by B7-H3 was detected both in vitro and in vivo . The expression of stemness-related markers was examined by reverse transcription quantitative polymerase chain reaction, Western blotting, and flow cytometry. Sphere formation assay was used to detect the sphere-forming ability. The underlying regulatory mechanism of B7-H3 on the stemness of GC was investigated by mass spectrometry and subsequent validation experiments. The signaling pathway (Protein kinase B [Akt]/Nuclear factor erythroid 2-related factor 2 [Nrf2] pathway) of B7-H3 on the regulation of glutathione (GSH) metabolism was examined by Western blotting assay. Multi-color immunohistochemistry (mIHC) was used to detect the expression of B7-H3, cluster of differentiation 44 (CD44), and Nrf2 on human GC tissues. Student's t -test was used to compare the difference between two groups. Pearson correlation analysis was used to analyze the relationship between two molecules. The Kaplan-Meier method was used for survival analysis. RESULTS: B7-H3 knockdown suppressed the stemness of GC cells both in vitro and in vivo . Mass spectrometric analysis showed the downregulation of GSH metabolism in short hairpin B7-H3 GC cells, which was further confirmed by the experimental results. Meanwhile, stemness characteristics in B7-H3 overexpressing cells were suppressed after the inhibition of GSH metabolism. Furthermore, Western blotting suggested that B7-H3-induced activation of GSH metabolism occurred through the AKT/Nrf2 pathway, and inhibition of AKT signaling pathway could suppress not only GSH metabolism but also GC stemness. mIHC showed that B7-H3 was highly expressed in GC tissues and was positively correlated with the expression of CD44 and Nrf2. Importantly, GC patients with high expression of B7-H3, CD44, and Nrf2 had worse prognosis ( P = 0.02). CONCLUSIONS B7-H3 has a regulatory effect on GC stemness and the regulatory effect is achieved through the AKT/Nrf2/GSH pathway. Inhibiting B7-H3 expression may be a new therapeutic strategy against GC.
Humans ; Cell Line, Tumor ; Neoplasm Recurrence, Local ; NF-E2-Related Factor 2/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Stomach Neoplasms

BACKGROUND: Synovectomy has been introduced into total knee arthroplasty (TKA) with the aim of relieving pain and inflammation of the synovium. However, there are no long-term, comparative data to evaluate the effect of synovectomy in TKA. This study was aimed at assessing pain, function, and complications in patients undergoing synovectomy during TKA for osteoarthritis (OA) at long-term follow-up. METHODS: This was a prospective randomized controlled trial of 42 consecutive patients who underwent staged bilateral TKA. Patients undergoing the first-side TKA were allocated to receive TKA with or without synovectomy followed by a 3-month washout period and crossover to the other strategy for the opposite-side TKA. The overall efficacy of both strategies was evaluated by determination of blood loss, the Knee Society score (KSS), and knee inflammation conditions during a 3-month postoperative period. The postoperative pain, range of motion (ROM), and complications were sequentially evaluated to compare the two groups until 10 years after surgery. RESULTS: At the 10-year follow-up, both groups had a similarly significantly improved ROM (114.88 ± 9.84° vs. 114.02 ± 9.43°, t  = 0.221, P  = 0.815) and pain relief with no differences between the two groups (1.0 [1.0] vs. 1.0 [1.5], U  = 789.500, P  = 0.613). Similar changes in total blood loss, KSS, and knee inflammation were found in both groups during 3 months postoperatively ( P  > 0.05). Additionally, there was no significant difference regarding complications and satisfaction between the two groups ( P  > 0.05). CONCLUSIONS: Synovectomy in conjunction with TKA for primary OA does not seem to provide any benefit regarding postoperative pain, ROM, and satisfaction during a 10-year follow-up. In addition, it may not result in more blood loss and increased incidence of long-term complications. Based on our long-term findings, it should not be performed routinely. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR-INR-16008245; https://www.chictr.org.cn/showproj.aspx?proj=13334 .
Humans ; Arthroplasty, Replacement, Knee/methods* ; Synovectomy/methods* ; Osteoarthritis, Knee/surgery* ; Prospective Studies ; Pain, Postoperative ; Inflammation/etiology* ; Range of Motion, Articular ; Knee Joint/surgery* ; Treatment Outcome ; Knee Prosthesis/adverse effects*

Cholestatic liver disease is a common disease that causes bile flow dysfunction due to various reasons. The etiology of cholestatic liver disease is complexed, and therapeutic drugs are extremely limited. To date, ursodeoxycholic acid is the only FDA-approved drug for treating primary biliary cirrhosis, whereas its efficacy is limited to early stage of the disease, therefore novel drugs are urgently needed. Nuclear receptors become therapeutic hotspot target in cholestasis since these receptors play a key role in regulating bile acid homeostasis. Peroxisome proliferator-activated receptor (PPAR) is an important nuclear receptor involved in regulating multiple mechanisms of cholestasis in vivo. It can improve intrahepatic cholestasis by inhibiting bile acid synthesis, reducing bile acid toxicity, affecting the expression of bile acid metabolic enzymes and transporters, and can play an anti-inflammatory, anti-oxidation and anti-fibrosis role. A number of studies have shown that PPAR agonists represented by fibrates alone or in combination can improve liver function indexes, inflammatory factors and fibrosis markers in patients with cholestasis. This review analyzes and summarizes the lastest advances in the molecular mechanism of PPAR as a therapeutic target for cholestasis and drug treatment in development or have been used in clinical.

Objective:To explore the feasibility of high-flow nasal cannula(HFNC)therapy for respiratory failure in elderly patients.Methods:A total of 300 patients with respiratory failure admitted to Peking University Shougang Hospital from December 2016 to March 2019 were enrolled in this prospective study.Patients were divided into three groups: the HFNC group, the conventional oxygen therapy(COT)group and the non-invasive positive pressure ventilation(NPPV)group(n=100 in each group). Arterial oxygen saturation(SPO 2), oxygen index(OI), heart rate(HR), respiratory rate(RR), mean arterial pressure(MAP), comfort level, discharge rate, tracheal intubation rate, rate of referral to ICU, mortality and rate of referral to another group after therapy were compared between the HFNC and COT groups and between the HFNC and NPPV groups. Results:SPO 2 after oxygen therapy for 30 minutes( t=-2.992, P=0.003), 1 hour( t=-2.884, P=0.005)and 6 hours( t=-3.196, P=0.002)and OI before discharge( t=-2.060, P=0.048)were higher in the HFNC group than in the COT group.The HR in the above two groups was lower before discharge than before therapy, and the HR in the COT group was even lower(73.1±25.1 beat per minute vs.75.1±25.9 beat per minute), but both were within the normal range.The discharge rate was higher( χ2=-1.969, P=0.049), while the rate of referral to another group was lower in the HFNC group than in the COT group( χ2=-3.115, P=0.002). There was no significant difference in the tracheal intubation rate, ICU transfer rate and mortality between the HFNC and COT groups.SPO 2 after oxygen therapy for 30 minutes( t=-2.026, P=0.046)and 6 hours( t=-2.101, P=0.040)were higher in the HFNC group than in the NPPV group, but there was no significant difference in OI and SPO 2 between the two groups before discharge.The HR in both HFNC and NPPV groups was lower before discharge than before therapy, and there was no statistical difference between the two groups.The mortality, discharge rate, tracheal intubation rate, ICU transfer rate and rate of referral to another group had no significant difference between the HFNC and NPPV groups.The comfort level was higher in the HFNC group than in the COT and NPPV groups( t=-3.758 and -19.180, both P=0.000). Conclusions:HFNC is a new type of oxygen therapy equipment introduced after COT and NPPV, and possesses more advantages for elderly patients with respiratory failure.

Objective:To investigate the relationship between painful tonic spasm (PTS) and spinal cord injury in patients with neuromyelitis optica spectrum disorder (NMOSD).Methods:The clinical data, serum AQP4-IgG antibody levels and magnetic resonance data of 138 patients with NMOSD were analyzed. Those with spinal cord involvement were assessed using the American Spinal Injury Association Impairment Scale (AIS) to investigate the relationship between PTS and spinal cord injury.Results:The prevalence of PTS among the NMOSD patients was 36% (51/138), and all of the 51 NMOSD patients with PTS showed spinal cord lesions, an incidence significantly different from those without PTS. However, there were no significant differences in the age of onset, gender, disease duration, AQP4-IgG levels, lesion location, range of spinal cord lesions, or AIS grade between the NMOSD patients with and without PTS.Conclusion:PTS is a prevalent concomitant of NMOSD. As a common symptom of remission and recurrent remission, PTS is associated with myelopathy. This study failed to find any correlation between PTS and the affected spinal cord site or segment range. There was also no correlation between PTS and AIS grading among these subjects.

Use of a BioEnterics intragastric balloon is a noninvasive,repeatable,low-cost,and safe method that can help in weight reduction. Injection of substances such as saline or air into a part of the stomach leads to a reduction in food intake and delays gastric emptying.This article aims to introduce the clinical application of different types of balloons and summarize the progress in treating obesity.

Objective Study on the absorption,distribution,transformation,excretion and toxicity of four forms of arsenic in rats.Methods Four thousand and fifty data were obtained from 28 days animal metabolism experiments of 81 rats exposed to the four As species.Distribution,metabolism,excretion,and subacute toxicity of 4 As species were compared by analyzing the arsenate [As(V)],arsenite [As(Ⅲ)],methyl arsenate (MMAV) and dimethyl arsenate (DMAV) content of rat feces (excrement and urine),blood,seven organs,and liver and kidney pathology.Results After oral administration of each As species,82.9％ of As(Ⅲ),85.1％ of As(V),95.0％ of MMAV and 96.2％ of DMAV were accumulatively secreted via feces and urine,while 16.2％ of As(Ⅲ),14.1％ of As(V),4.65％ of MMAV and 0.120％ of DMAV were detected in blood.The DMAV accumulated in blood and urine after dosing As(Ⅲ),As(V) and MMAV,and the content of DMAV in the blood was 8 times greater than urine.Four kinds of arsenic had effects on rat liver and kidney function,the influence on liver was acute phase effect while that on renal was cumulative effects.The effect of As(Ⅲ) was the most significant,followed by MMAV.Four kinds of arsenic could cause tissue deformation and inflammatory cells infiltration,but showed no difference between groups.Conclusion The distribution,metabolism,excretion,and toxicity of the four kinds of arsenic in rats were different in varying degrees.The research of health risk for arsenic should consider its different forms.

Objective to determine the basal levels of several pancreas-related endocrine hormones in patients with chronic pancreatitis.Methods according to inclusion and exclusion criteria,consecutive patients from February 2016 to August 2016 in Department of Gastroenterology,Changhai Hospital,Second Military Medical University and ten healthy control (matched for age and gender) were included.Basal levels of glucagon-like peptide 1,pancreatic polypeptide,Secretin,glucagon,somatostatin between groups of CP vs healthy control,CP with abnormal glycometabolism vs CP with normal glycometabolism and alcoholic CP vs non-alcoholic CP were compared.Results a total of 53 patients with chronic pancreatitis and 8 healthy subjects were included in this study.(1) CP vs healthy controls:the level of secretin in healthy control patients is significant lower than that in CP patients;(2) CP with abnormal glycometabolism vs CP with normal glycometabolism:the level of triglyceride and somatostatin is significant lower than that in CP patients;the prevalence of patients with chronic alcohol consumption and the level of glucagon-like peptide 1 in CP with abnormal glycometabolism is significant higher than that in CP with normal glycometabolism;(3) the prevalence of abnormal glycometabolism in alcoholic CP group is significant higher than that in non-alcoholic CP.The results above are all of statistical significance.Conclusions in addition to dysfunction of islets/3-cells,CP also easily affects the level of other pancreas-related hormones such as secretin,somatostatin and glucagon-like peptide 1.Otherwise,chronic alcohol consumption is also strongly related with abnormal glycometabolism,the mechanism deserves further researches.

Gastric disease is a great burden in China; chronic gastritis, gastric ulcer, and gastric cancer incidences are the highest in the world.However,the screening rate of gastric disease in China is low because endoscopy and other screening methods are not accepted widely and they consume large amounts of manpower and material resources.The screening of gastric cancer has not been implemented,leading to high mortality because of gastric cancer. In recent years, the rapid development of magnetic-controlled capsule endoscopy provides a painless,highly accepted screening method for gastric cancer and other diseases.This article aims to introduce clinical applications of magnetic-controlled capsule endoscopy in screening and early diagnosis of stomach diseases.

Objective To investigate the feasibility and safety of three-dimensional video-assisted thyroidectomy (3D VAT). Methods During January to April of 2014, 10 cases with unilateral or bilateral thyroid benign diseases , thyroid cancer, or parathyroid lesions were enrolled .The 3D VAT was carried out by using a 10-mm 3D stereoscopic endoscope .Local excision or lobectomy was performed via a 2-4 cm curve skin incision one finger above the sternal notch .In two patients , lobotomy combined with systematic lymphadenectomy was performed when papillary thyroid microcarcinoma was identified during operation . Results All the procedures were accomplished successfully under 3D video-assisted system, without intra-operative abnormal blood loss or conversion to conventional thyroidectomy .The operative time was 30-90 min (61.8 ±22.4 min);the intra-operative blood loss was 1.3-93.0 g (median, 5.2 g).All the patients were followed up for 1-4 months.Neither intra-nor post-operative complications about recurrent laryngeal nerve , superior laryngeal nerve , or parathyroid were observed . Conclusions Preliminary impression emerging from this study seems to suggest that 3D VAT is safe and effective.Compared with 2D surgery, a good perception of depth and easy recognition of anatomic structures are noticeable .