Islet β cell protection is one of the key strategies for diabetes treatment. The new antidiabetic drug sodium-glucose cotransporter 2(SGLT2)inhibitor decreases blood glucose by inhibiting glucose reabsorption in the renal tubule, independent of insulin. Various clinical studies have shown that SGLT2 inhibitors improve β cell function. Furthermore, animal experiments have indicated that SGLT2 inhibitors increase β cell mass. SGLT2 inhibitors promote islet regeneration through stimulating β cell proliferation, inhibiting β cell apoptosis and dedifferentiation, enhancing transdifferentiation of α cells to β cells, and initiating progenitor-derived β cell neogenisis. Indirect effects of metabolic improvement(i.e.lowering glucose, losing weight, improving lipid metabolism), inhibiting inflammatory reaction, inducing glucagon-like peptide-1 secreted from α cells, and regulating gene changes might be involved in the β cell protection of SGLT2 inhibitors.

Objective To explore the diagnosis and treatment of tumor associated gastrocolic fistula (GCF).Methods The records of the 4 patients with GCF between August 2008 to February 2014 were retrospectively analyzed.Three female and one male patients,those whose average age were 61 years,have been pathologically diagnosed postoperatively as gastrocolic fistula caused by malignant diseases.The main clinical symptoms were diarrhea (3 cases),fecal vomitus (3 cases),weight loss (4 cases),and abdominal pain (4 cases).Positive diagnostic tests for GCF included gastroscope (3 cases),colonoscope (1 case),barium enema (1 case),upper gastrointestinal contrast (2 cases).Results En-bloc resection of the involved gastrocolic region have been performed for all,2 patients underwent radical gastrectomy and colon resection and 2 patients were taken on palliative procedure.Pathology indicated adenocarcinoma all,Immunohistochemical detection for CK20,CDX-2 were applied for identifying the originations of tumors.Delayed gastric emptying and DIC occurred in one patient who died in 3 months after the operation,anastomotic leakages were found in 2 cases.The survival patients were all discharged and taken capecitabine combined with Oxaliplatin for chemotherapy.Conclusions Endaoscopy and gastrointestinal imaging are main evidences for diagnosis of GCF.En-bloc resection of the involved gastrocolic region were recommended,enterostomy was safer than entero-anastomosis in one stage procedure.The originations of tumors may be identifying according to the pathological characteristic and CDX-2,CK20 staining.Adjuvant chemotherapy should be applied.

Objective This study aimed to establish a prediction system of lymph node metastasis of gastric cancer patients,to facilitate guiding the treatment of patients with gastric cancer.Method s We analyzed 255 cases of gastric cancer from January 2005 to December 2009 in Beijing Friendship Hospital.They all had surgery or palliative gastrectomy and then examined pathological lymph node metastasis.Their gender,age,preoperative weight loss,anemia,pyloric obstruction,chronic disease history,family history,tumor location,tumor size,higher preoperative CEA,preoperative tumor markers (CEA,AFP,CA199,CA125)elevationed (one or more),preoperative choline esterase,preoperative albumin,preoperative hemoglobin,preoperative platelet and preoperative urinary protein were made Logistic regression analysis.Results The combination of preoperative tumor size,higher tumor markers (CEA,AFP,CA199,CA125) in one or more was possible for lymph node metastasis prediction.The area under ROC curve was about 100%,Showing high discriminant ability.Conclusions The tumor size and preoperative tumor markers (CEA,AFP,CA199,CA125) are important predictive parameters for lymph node metastasis of gastric cancer.Tumor size combined with the preoperative tumor markers (CEA,AFP,CA199,CA125) predicting lymph node metastasis can help us to carry out other work,such as neoadjuvant therapy,etc.

Objective To investigate the efficacy and toxicity of neoadjuvant chemotherapy of modified FOLFOX7 regimen in the treatment of advanced gastric cancer. Methods The clinical data of 30 patients with advanced gastric cancer who had been admitted to Beijing Friendship Hospital from June 2005 to January 2009 were retrospectively analyzed. All patients received modified FOLFOX7 regimen [oxaliplatin (100 mg/m~2) + fluorouracil (2400 mg/m~2) + calcium folinate (400 mg/m~2)] for 2-4 courses before operation. The efficacy and toxicity of the modified FOLFOX7 were evaluated before and after the operation. All data were analyzed via chi-square test. Results The pre-and postoperative downstaging rates were 27% (8/30) and 47% (14/30), respectively. The total effective rate of modified FOLFOX7 regimen was 43% (13/30). Complete remission was observed in 1 patient. The toxicity was mild. Radical resection was accomplished in 28 patients (93%). There was no statistical difference between the 2 criteria in evaluating the efficacy of modified FOLFOX7 regimen (χ~2= 2.584, P>0.05). Conclusion Modified FOLFOX7 regimen is effective and well-tolerable for patients with advanced gastric cancer.

Hepatoid adenocarcinoma of the stomach (HAS) is defined as a special type of gastric cancer characterized by low incidence rates and high degree of malignance with an extremely poor prognosis.As it is characterized by morphological similarities to general alimentary cannal symptoms with unclear etiology and pathogenesis,diagnostic errors can always be made.The alpha-fetoprotein (AFP) and carcino-embryonic antigen (CEA) are helpful with diagnosis.However,histopathological examination is the gold standard for diagnosing HAS.So far,radical operation,adjuvant chemotherapy,interventional therapy with immune-biological treatment are the main approaches for HAS treatment.

OBJECTIVETo verify the clinical safety of complete mesocolic excision (CME) and manufacture pathological large slices.

METHODSA prospective analysis clinical data of 85 right colon cancer in patients by the same group of surgeons at the Department of General Surgery, Beijing Friendship Hospital, Capital Medical University from January 2012 to December 2013 which were divided into two groups: CME group (n=39) and traditional radical operation group (n=46) by surgical approach. CME group and control group were compared the differences of clinic and pathologic variables, precise tissues morphometry, lymph nodes harvest, mesocolic area and so on. By comparison to operation time, blood loss, postoperative complications, flatus restoring time, drainage removal time and length of stay, the security of CME was analyzed. Statistical methods included independent sample t-test, Wilcoxon rank sum test and χ(2) test. In order to manufacture pathological large slices, the CME operation specimens were fixed. The large slices were stained by routine HE staining to detection of circumferential resection margin.

RESULTSMean number of total lymph nodes was increased obviously in CME group (26.8±1.9 vs. 23.2±3.4, t=4.261, P=0.000). Mean number of lymph nodes of stage Ⅰ, Ⅱ were different between two groups (25.8±3.6 vs. 18.2±4.5, 26.8±7.7 vs. 24.9±6.2, t=8.776, 2.802, P=0.000). The positive lymph nodes of CME group was higher than control group (4(7) vs. 1.5(2), P=0.032), above all with statistically significant difference. Comparing CME group with the control group, there were the larger area of mesentery ((15 555±1 263) mm(2) vs. (12 493±1 002) mm(2,) t=12.456, P=0.000), the greater distance between the tumor and the high vascular tie ((116±22) mm vs. (82±11) mm, t=9.295, P=0.000), the greater distance between the normal bowel and the high vascular tie ((92±17) mm vs. (74±10) mm, t=8.132, P=0.000) of CME, with statistically significant difference. There were no statistically significant differences from operation safety when CME group was compared with the control group. The pathological large slices of colon cancer were prepared successfully and dyed evenly than those large slices were used to observe whether the lymph tube and lymph node metastasis inside the mesocolon. Existence of direct tumor invasion could be confirmed by investigating the large slices. Cancer embolus in intravascular and micro infiltration in mesocolon also could be found.

CONCLUSIONSCME operation can get the standard excision according the mesocolic area and integrity, as well as to harvest the maximum number of lymph node. The clinical application of CME is safe and does not increase the risk of operation. Circumferential resection margins can be detected by pathological large slices.

Colectomy ; Colonic Neoplasms ; surgery ; Device Removal ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Mesocolon ; surgery ; Operative Time ; Postoperative Complications ; Prospective Studies

Objective:To investigate the efficacy of a SARS-CoV-2 recombinant protein vaccine as a booster dose.Methods:A new immunogen, namely RBD-sc-trimer, was designed by tandem repeating of single receptor binding domain (RBD) of SARS-CoV-2 spike (S) protein to mimic the trimeric form of RBD presented by the virus. The RBD-sc-trimer protein was expressed as a His-tagged fusion protein using a baculovirus expression system and purified by nickel affinity column. The purified protein was identified by Western blot. Its in vitro binding activity to human angiotensin converting enzyme 2 (hACE2) was analyzed by ELISA. The immunogenicity of RBD-sc-trimer as well as RBD proteins of other forms including RBD dimer (RBD-Fc), RBD monomer (RBD) and S protein trimer (S trimer) as a booster dose was evaluated in BALB/c mice. Results:In terms of both binding and neutralizing antibodies against SARS-CoV-2, RBD-sc-trimer showed an immunogenicity that was superior to that of RBD-Fc and RBD and close to the level of S trimer. The antibody response induced by RBD-sc-trimer was characterized as Th1-biased. Moreover, it displayed a stronger cross-neutralization activity against SARS-CoV-2 Beta, Delta and Omicron variants. The titer of neutralizing antibody against Omicron induced by RBD-sc-trimer only decreased by 9.1 folds relative to the prototype strain, while the antibody response induced by RBD-Fc and S trimer decreased by 68.4 and 70.8 folds, respectively.Conclusions:The recombinant protein, RBD-sc-trimer, which was capable of eliciting stronger humoral response in mice as a booster dose and showed the superiority in raising cross-reactive antibodies against SARS-CoV-2 variants over non-trimeric RBD forms, should be considered as an optimal immunogen for the development of more effective SARS-CoV-2 vaccines.

OBJECTIVE: To explore the effects and mechanisms of the long-snake moxibustion on ankylosing spondylitis (AS) based on Th17/Treg/Th1 immune imbalance. METHODS: A total of 60 AS patients were randomized into an observation group and a control group, 30 cases in each one. In the observation group, the long-snake moxibustion therapy was used on the acupoints of the governor vessel from Dazhui (GV 14) to Yaoshu (GV 2) as well as the bilateral Jiaji (EX-B 2) alternatively. The moxibustion was given once a day, for 7 days continuously as one course. There were 3 days at the interval between the courses and 4 courses were required. In the control group, the routine western medication was provided, the salazosulfapyridine combined with non-steroidal anti-inflammatory drugs were used, for 7 days continuous as one course. A total of 4 courses of medication were required. The enzyme linked immunosorbent assay (ELISA) was adopted to determine the levels of interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-23 (IL-23) and tumor necrosis factor-α (TNF-α). The real-time quantification polymerase chain reaction (RT-PCR) was used to determine the mRNA expressions of the specific transcription factors, FoxP3 and T-bet of the helper 17 cells (Th17), regulatory T cells (Treg) and T helper 1 cells (Th1). The flow cytometry was applied to determine the rates of Treg, Th1 and Th17, as well as the changes of the inflammatory reaction index, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The therapeutic effects were compared between the two groups. RESULTS: After treatment, the total effective rate was 93.3% (28/30) in the observation group, which was better than 86.7% (26/30) in the control group (<0.05). After treatment, the levels of CRP, ESR, IL-6, IL-17, IL-23 and TNF-α, as well as the rate of Th17 were reduced significantly as compared with those before treatment in the observation group (all <0.05). The mRNA expressions of FoxP3 and T-bet and the rates of Treg and Th1 were increased as compared with those before treatment (all <0.05). The change degree in the observation group was significant as compared with the control group (all <0.05). In the control group, the levels of CRP, ESR, IL-6, IL-17, IL-23 and TNF-α, as well as the rate of Th17 were reduced, and the mRNA expressions of FoxP3 and T-bet and the rates of Treg and Th1 were increased after treatment. But the changes were not significant as compared with those before treatment (all >0.05). CONCLUSION The long-snake moxibustion effectively relieves the clinical symptoms in AS patients and regulates the Th17/Treg/Th1 immune imbalance. Its effect target is probably related to the modulation of the AS immune derangement and the inflammatory responses induced by immune derangement so as to achieve the dual-positive regulatory effect.
Animals ; Humans ; Lymphocyte Count ; Moxibustion ; Snakes ; Spondylitis, Ankylosing ; therapy ; T-Lymphocytes, Regulatory ; Th1 Cells ; Th17 Cells

Drug-device combination product, which comprises at least a drug and a medical device, has been proved to effectively reduce the risk of complications accompanied with conventional medical devices implantation, and has a great clinical success especially in implantable therapeutics. Herein, we firstly elaborated the definitions and requirements of drug-device combination product in different countries, then summarized the market application and research development of typical drug-device combination products. Technical problems and the trend of future development had also been analyzed.
Drug Delivery Systems/instrumentation* ; Equipment Design ; Prostheses and Implants

Sensory conflict impacts postural control, yet its effect on cortico-muscular interaction remains underexplored. We aimed to investigate sensory conflict's influence on the cortico-muscular network and postural stability. We used a rotating platform and virtual reality to present subjects with congruent and incongruent sensory input, recorded EEG (electroencephalogram) and EMG (electromyogram) data, and constructed a directed connectivity network. The results suggest that, compared to sensory congruence, during sensory conflict: (1) connectivity among the sensorimotor, visual, and posterior parietal cortex generally decreases, (2) cortical control over the muscles is weakened, (3) feedback from muscles to the cortex is strengthened, and (4) the range of body sway increases and its complexity decreases. These results underline the intricate effects of sensory conflict on cortico-muscular networks. During the sensory conflict, the brain adaptively decreases the integration of conflicting information. Without this integrated information, cortical control over muscles may be lessened, whereas the muscle feedback may be enhanced in compensation.
Humans ; Muscle, Skeletal ; Electromyography/methods* ; Electroencephalography/methods* ; Brain ; Brain Mapping