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Objective:To investigate the efficacy and prognostic survival of pembrolizumab combined with apatinib and chemotherapy in the treatment of human epidermal growth factor receptor-2 (HER2)-negative advanced gastric cancer.Methods:Patients with HER2-negative advanced gastric cancer were selected from December 2019 to December 2022 as the study subjects. Forty-five patients who received chemotherapy therapy (fluorouracil+cisplatin) were randomly collected and included in control group, and 52 patients who were treated with pembrolizumab combined with apatinib were randomly selected and enrolled as observation group. The difference in short-term efficacy was compared. The levels of serum tumor markers and immune function (CD3 +, CD4 +, CD8 +, CD4 +/CD8 +) were recorded. The long-term efficacy and adverse reactions of patients were compared. Measurement data conforming to the normal distribution were expressed as xˉ± s, and the mean comparison between groups was performed by independent sample t test. Chi-square test was used to compare the rate or composition ratio among enumeration data. P<0.05 was considered statistically significant. Results:At 6 months after treatment, the disease control rate in observation group was significantly higher than that in control group (78.85% (41/52) vs 57.78% (26/45)) ( χ2=5.01, P=0.025), but there was no statistical significance in objective response rate between groups (36.54% (19/52) vs 24.45% (11/45)) ( χ2=1.65, P=0.199). The levels of pepsinogen I, tissue polypeptide specific antigen, carcinoembryonic antigen, carbohydrate antigen 199 and CD8 + in both groups were reduced after treatment, and the levels were lower in observation group than those in control group ( t=6.06, 6.78, 4.68, 11.21, 3.45, all P<0.001). The levels of CD3 +, CD4 + and CD4 +/CD8 + were enhanced significantly in the two groups, and the observation group had higher levels after treatment ( t values were 2.10, 3.74, and 5.19; P values were 0.028, <0.001, and <0.001). After 1 year of follow-up, the survival rate in observation group with 59.62% (31/52) was significantly higher than 37.78% (17/45) in control group ( χ2=4.60, P=0.032). The progression-free survival time ((10.22±1.62) months vs (8.13±1.57) months, t=6.43, P<0.001) and overall survival time ((11.62±1.84) months vs (9.73±1.71) months, t=5.21, P<0.001) in observation group were significantly longer compared to control group. There were no statistical differences in the incidence rates of bone marrow suppression ( χ2=1.92, P=0.165), hand-foot syndrome ( χ2=3.47, P=0.062), gastrointestinal reaction ( χ2=0.32, P=0.574), hypertension ( χ2=0.94, P=0.333) and proteinuria ( χ2=2.39, P=0.122) between the two groups. Conclusion:Compared with chemotherapy, pembrolizumab combined with apatinib shows good short-term efficacy and long-term efficacy in patients with HER2-negative advanced gastric cancer.

Objective:To explore the application value of flexible endoscopy and rigid endoscopy in the clinical examination of chronic sinus tract wounds with different shapes.Methods:A retrospective observational study was conducted. From January 1 to December 23, 2019, a total of 46 patients with chronic sinus tract wounds, who met the inclusion criteria were admitted to the Wound Healing Center of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, including 23 males and 23 females, aged 18-81 (48±21) years. On admission, computer tomography (CT) imaging and three-dimensional reconstruction were performed to examine the shapes of wound sinus tract and classify the wounds, with the lengths of wound sinus tract by CT imaging examination (hereinafter referred to as reference lengths) recorded. The lengths of wound sinus tract were examined and measured by rigid endoscopy and flexible endoscopy. The wounds with and without obviously curved sinus tract were classified into curve group and linear group respectively, and the deviation rates between the lengths of wound sinus tract measured by flexible endoscopy or rigid endoscopy and the reference lengths (hereinafter referred to as deviation rates of lengths) in each group were calculated. The difference between the deviation rates of lengths examined by flexible endoscopy and rigid endoscopy and the differences between the above two and the deviation rate of reference lengths (0) in each group were compared. Data were statistically analyzed with paired sample t test and Wilcoxon signed rank sum test. Results:CT imaging and three-dimensional reconstruction showed that there were 4 types of wound sinus tract, including tubular (36/46), lamellar (4/46), club-mallet (4/46), and irregular (2/46) shape. Tubular wounds were further divided into type I (23/36), type L (4/36), and type Y (9/36). Wounds with type I tubular, lamellar, and club-mallet sinus tract were classified into linear group (31/46), while those with type Y tubular, type L tubular, and irregular sinus tract were classified into curve group (15/46). In linear group, the deviation rates of lengths examined and measured by rigid endoscopy and flexible endoscopy were 0. In curve group, the deviation rate of lengths examined and measured by flexible endoscopy was 0 (0, 0.58%), which was significantly lower than 41.18% (31.68%, 48.41%) examined and measured by rigid endoscopy, Z=-3.408, P<0.01; the deviation rate of lengths examined and measured by rigid endoscopy (40±19)% was significantly higher than the deviation rate of reference lengths ( t=8.343, P<0.01), while the deviation rate of the lengths examined and measured by flexible endoscopy was similar to the deviation rate of reference lengths ( Z=-1.342, P>0.05). Conclusions:Compared with rigid endoscopy, flexible endoscopy can observe the internal characteristics of chronic sinus tract wounds in a wider range in the clinical examination of this kind of wound, especially for the exploration of curved chronic sinus tract wounds. The promotion of this method will be conducive to the diagnosis and treatment of chronic sinus tract wounds.

Objective:To investigate the clinical features and prognosis of pediatric autoimmune encephalitis associated with anti-glutamic acid decarboxylase 65 (GAD65) antibody.Methods:Clinical data of 2 patients diagnosed as autoimmune encephalitis associated with anti-GAD65 antibody at Department of Neurology, Beijing Children′s Hospital in 2019 were analyzed retrospectively. A literature search with “anti-GAD65 antibody”“encephalitis”“epilepsy” or “cerebellar ataxia” as key words was conducted at China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform and PubMed (up to January 2020). The clinical features and prognosis of pediatric cases with complete clinical data were retrieved and summarized.Results:Two patients with positive anti-GAD65 antibody of serum and cerebrospinal fluid were both females. The onset age of case 1 was 57 months and her main clinical manifestations were fever and unconsciousness. The cranial magnetic resonance imaging (MRI) showed diffuse T2 weighted imaging (T2WI) abnormal signals, and the electroencephalogram (EEG) showed slow waves. The onset age of case 2 was 80 months and her main clinical manifestations of were recurrent focal seizures, memory loss, and headache. The MRI showed high T2WI signal in bilateral hippocampus, and the EEG showed abnormal discharge involving the temporal area. Both cases were treated with methylprednisolone and intravenous immunoglobulin, the short-term symptoms of them were both improved. They were followed up for 6 months and 1 year respectively, the case 1 recovered completely, and the case 2 still had focal seizures. Six English reports which included 6 cases were retrieved. Together with these 2 cases, a total of 8 cases were analyzed. The clinical symptoms included seizures (6 cases), memory loss (4 cases), loss of consciousness (3 cases), behavioral abnormalities (3 cases), cognitive impairment (2 cases), headache (2 cases), autonomic symptoms (1 case), ataxia (1 case), dysphagia (1 case), and aphasia (1 case). There were 5 cases with cranial MRI abnormalities in the acute phase or sub-acute phase, of whom 3 cases had the limbic system involvement, and 2 cases were mainly had extra limbic area involvement. Three cases had hippocampal atrophy or sclerosis during follow-up. All 8 patients were treated with immunotherapy. After immunotherapy, all patients had short-term improvement. Follow-up for 6 months to 6 years showed that 3 cases with extra limbic encephalitis improved to baseline levels, and 5 limbic encephalitis cases had poor outcomes, including 1 death and 4 cases still had focal epilepsy.Conclusions:Pediatric anti-GAD65 antibody associated autoimmune encephalitis is a rare but treatable disease, including limbic encephalitis and extra limbic encephalitis. The most common clinical manifestations are seizures and memory impairment. Early diagnosis and immunotherapy can improve the symptoms in a short time. But patients with limbic encephalitis often had refractory epilepsy in the chronic phase, and have a poor long-term outcome.

Objective To detect 10 kinds of human milk oligosaccharides (HMOS) and compare their amounts during lactational stage.Methods Breast milk samples in different stages of lactation as colostrum (day 0-7 postpartum),transitional milk (day 8-15 postpartum),and mature milk (day 16-180 postpartum) were collected and 10 HMOS in those samples were detected and quantified by ultra high performance liquid chromatography-fluorescence detection after fluorescence labeling by using standard curves.Correlations between HMOS and lactation day were conducted by Person correlation analysis method,while the differences among three stages were calculated by ANOVA test.Results Ten HMOS were successfully separated and quantified under chosen chromatographic parameters.2'FL,3'SL,6'SL,LNT,LNnT and LNFP-I were negatively correlated and 3'FL was positively correlated with lactation days.They were different in three lactational stages (P ＜ 0.05),while P1,LNFP-V and LNnFP-V showed no correlation and difference (P ＞ 0.05).Conclusion The amount of HMOS changed during lactational stages.Seven HMOS were correlated with lactation days and different in three lactational stages (P ＜ 0.05).

Objective To obtain a thyroid cancer cell line integrated with luciferase and fluorescence,and to establish a metastatic nude mouse model of papillary thyroid cancer monitored with in vivo imaging system. Methods Lentivirus carrying recombinant plasmid containing luciferase gene and mCherry gene infected high malignant papillary thyroid cancer cell line (BHP10-3SCmice). The stable thyroid cancer cell line (BHP10-3mluc) labeled with luciferase and mCherry selected by hygromycin, analyzed for fluorescence with fluorescence microscopy and bioluminescence with in vitro analysis and in vivo imaging. 0.25 ml(5×106/ml)BHP10-3mluc cell suspension were injected into the left thigh intramuscular tissue of 5-week-old nude mice to establish BALB/C nude mice metastatic tumor model. The growth and metastasis of the tumors were monitored weekly with in vivo imaging system. The nude mice were sacrificed on the 42th day and the tissues with metastatic tumors were analyzed by fluorescent imaging ex vivo. The ectopic implanted tumors and metastatic lesions were verified by tissue sections with Hematoxylin and Eosin staining. Results BHP10-3mluc cells showed similar growth characteristics to the original BHP10-3SCmice cells and stably expressed luciferase and mCherry. At the end of the first week after ectopic implantation,the xenograft tumors were found and in the 6th week,the tumors were found to metastasized to adjacent lymph nodes and lungs,which was consistent with the results of pathology.The growth and metastasis of tumors can be accurately monitored with in vivo imaging system. Conclusions A PTC cell line stably expressing bioluciferase and fluorescence was successfully established.The nude mouse model of PTC metastatic tumor generated by intramuscular inoculation of those cells can be well monitored with in vivo imaging system, which provides ideal models for researches on tumor growth, metastasis,and drug treatment.

Objective To find out the distribution of TCM constitution on the patients with stroke in Beijing. Method The TCM Constitution Questionnaire was used to evaluate 489 patients with stroke in three hospitals in Beijing. Results The qi-deficiency constitution (140 patients, 28.63%), yin-deficiency constitution (95 patients, 19.43%), blood-stasis constitution(89 patients, 18.20%) and phlegm-heat constitution (73 patients, 14.93%) were the most common constitution, while qi-depression constitution (22 patients, 4.50%) and yang-deficiency constitution (20 patients, 4.09%) were the less common. The top three constitution in middle aged wereqi-deficiency (33 patients, 27.27%), phlegm-heat (23 patients, 19.01%) and blood stasis (22 patients, 18.18%). The top three constitution in the aged groupwere qi-deficiency (107 patients, 29.08%), yin-deficiency (76 patients, 20.65%) and blood-stasis (67 patients, 18.21%). Conclusions Stroke is closely related with imbalance of TCM constitution. The prevention and treatment of stroke patients with different ages should vary according to the constitutions.