Inflammatory bowel disease (IBD) is characterized by recurrent non ⁃ specific intestinal inflammatory responses. Intestinal fibrosis is an important cause of IBD complicated with intestinal obstruction. Nuclear factor erythroid 2⁃ related factor 2 (Nrf2) is a transcription factor that has anti ⁃ oxidative stress response in cells. In IBD, Nrf2 and its downstream regulated antioxidant enzymes achieve protective effects against intestinal fibrosis by inhibiting the activation of nuclear factor ⁃ κB, regulating T helper cell 17/regulatory T cell balance of intestinal immunity, and inhibiting transforming growth factor⁃β1/Smads signaling pathway. In this review, the structure of Nrf2, the specific mechanism of Nrf2's effect on intestinal fibrosis in IBD, and the recent studies on the treatment of IBD through Nrf2 pathway were reviewed in an attempt to provide a new direction for the prevention and treatment of IBD.

As a part of the multidisciplinary diagnosis and treatment model of malignant tumors， traditional Chinese medicine （TCM） plays a unique role in increasing efficiency， reducing toxicity， and preventing recurrence and metastasis. It has been gradually recognized that integrated TCM and western medicine should be used in diagnosis and treatment of tumors. Western medicine such as surgery， radiotherapy， chemotherapy， endocrine therapy， targeted therapy， and immunotherapy may act as the main factors that change the syndromes， as they can induce the changes of the tongue and pulse manifestations and symptoms after acting on the body. It is therefore advised to differentiate and analyze the attributes of yin-yang and cold-heat of western medicine as well as its impact on TCM syndromes， and use Chinese herbal medicinals precisely so as to increase efficiency and reduce toxicity. Moreover， it is better to grasp the syndrome evolution trend of modern medicine and predict the disease tendency， so as to improve the accuracy of syndrome differentiation and treatment in TCM under multi-disciplinary diagnosis and treatment model， and promote the maximization of the benefits of integrated TCM and western medicine in treating tumors.

Objective:To investigate the clinical characteristics of congenital esophageal atresia with gastric perforation, and to improve pediatricians′ understanding of this disease.Methods:The clinical data of five neonates with congenital esophageal atresia and gastric perforation treated in the neonatal intensive care unit of the Affiliated Hospital of Qingdao University from 2012 to 2022 were analyzed retrospectively.Results:Among the five neonates, four were boys and one was girl.The gestational age was 28 + 5 to 37 + 6 weeks, the birth weight was 1 100~2 350 g. All of them had dyspnea and feeding difficulties after birth.Gastric perforation occurred in three cases during invasive mechanical ventilation, one case during non-invasive ventilation, and one case during nasal catheter oxygen inhalation.Emergency primary gastric repair was performed, followed by secondary esophageal anastomosis.All the patients were cured and discharged from hospital. Conclusion:Gastric perforation is a rare complication of congenital esophageal atresia, which is more common in premature infants and low birth weight infants.Mechanical ventilation may promote the occurrence of gastric perforation.If gastric perforation is complicated, repair should be performed as soon as possible, and esophageal anastomosis surgery should be performed early after stability to improve the final outcome.

Objective:To investigate the effect of Mini-Clinical Evaluation Exercise (Mini-CEX) combined with direct observation of procedural skills (DOPS) in ophthalmology practice training in the integrated teaching of sensory system diseases.Methods:The medical students in the five-year program who entered the stage of ophthalmology practice in the integrated teaching of sensory system diseases in The Second Clinical College of Chongqing Medical University, were selected as research group, and the medical students in the five-year program who received training from October 2020 to July 2021 were selected as control group. The two groups were compared in terms of department examination score, progressive evaluation of the research group, and the degree of satisfaction with practice. SPSS 23.0 was used for the t-test. Results:Compared with the control group, the research group had significantly better scores of medical history inquiry, medical record writing, and operational skills ( t=2.47, P=0.016; t=5.26, P<0.001; t=2.20, P=0.031). In progressive training, the Mini-CEX and DOPS scores in the second progressive formative assessment were better than those in the first assessment ( t=-21.06, P<0.001; t=-15.09, P<0.001). The degree of satisfaction with performance among the interns and the degree of satisfaction with interns among the examiners in the second assessment were better than those in the first assessment ( t=-5.53, P<0.001; t=-8.19, P<0.001). Conclusion:Mini-CEX combined with DOPS has a good effect in ophthalmology practice training in the integrated teaching of sensory system diseases and thus holds promise for application.

BACKGROUND: Epidermal growth factor receptor (EGFR) and cellular-mesenchymal to epithelial transition factor (c-Met) are widely expressed on cancer cells. There is a synergistic effect of EGFR and HGF/c-Met pathways on proliferation, downstream activation of signal transduction and an additive effect. Studies show that combination of both signaling pathways could potentially be targeted in a synergistic fashion. Amivantamab, a bispecific monoclonal antibody targeting EGFR and c-Met, yielded robust and durable responses in a variety of clinicals trials. However, few researches have reported its efficacy in Chinese non-small cell lung cancer (NSCLC) patients. This study was conducted to evaluate the effectiveness and tolerance of Amivantamab in NSCLC patients with EGFR/MET gene abnormalities at Peking University Cancer Hospital. METHODS: The study enrolled NSCLC patients who received Amivantamab in our hospital between August 2020 and December 2021, and analyzed the response, survival, and treatment-related adverse events. RESULTS: Fifteen patients were enrolled in this research, and six of them received Amivantamab treatment and the other nine patients received Amivantamab plus Lazertinib treatment. The rates of partial response (PR), stable disease (SD), and progressive disease (PD) were 46.7% (7/15), 46.7% (7/15) and 6.7% (1/15), respectively. The overall response rate (ORR) and disease control rate (DCR) were 28.6% (2/7) and 100.0% (7/7) in seven patients with EGFR exon 20 insertion, respectively. The ORR and DCR were 40.0% (2/5) and 100.0% (5/5) in five post-osimertinib EGFR-mutant patients, respectively. After a median follow-up of 8.7 months, the median progression-free survival and overall survival were not reached. The most common treatment-related adverse events were rash (86.7%), paronychia (80.0%), and infusion-related reactions (60.0%), and most of them were graded as 1 to 2. Grade 3 to 4 adverse events included rash (33.3%), alanine aminotransferase elevation (13.3%), gamma-glutamyl transpeptidase elevation (13.3%), peripheral edema (6.7%), thromboembolism (6.7%), interstitial lung disease (6.7%), and thrombocytopenia (6.7%). CONCLUSIONS Amivantamab was effective in Chinese NSCLC patients with EGFR exon 20 insertion and post-Osimertinib EGFR-mutant patients, similar to the results of clinical trials conducted in western countries. Amivantamab was well tolerated and emphases should be put on adverse events such as rash, paronychia, and infusion-related reactions.
Antibodies, Bispecific ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Exanthema/drug therapy* ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Paronychia/drug therapy* ; Protein Kinase Inhibitors/therapeutic use*

Objective:To explore an ideal method for establishing a mouse model of chronic atrophic gastritis (CAG).Methods:CAG mouse models were established with five different modeling methods ( N-methyl- N′-nitro- N-nitrosoguanide (MNNG), sodium salicylate, sodium deoxycholate, Helicobacter pylori infection, and combinations of them) in BALB/c and C57 mice. The effect of each modeling method was evaluated by histological observation of gastric mucosa, plasma biochemical parameters, inflammatory response score, and the expression of anti-inflammatory factors. Results:The results of histological observation of gastric mucosa showed that all of the 5 methods could successfully establish CAG mouse models. In BALB/c mice, compared with the healthy control group, significant features of CAG accompanied with intestinal metaplasia was found in the model group established by combination of MNNG-free drinking, 2% sodium salicylate and 20 mmol sodium deoxycholate. From the results of serological detection, compared with the normal control group, the mRNA expression levels of related anti-inflammatory factors interleukin-2, interleukin-10, interleukin-13 and growth differentiation factor-15 of each model group decreased, which indicated that the mice of each CAG model group had different degrees of inflammation. The results of plasma biochemical parameters indicated that plasma gastrin of each group decreased and the ratio of pepsinogen Ⅰ and pepsinogen Ⅱ significantly dropped. The above results demonstrated that in BLAB/c mice, MNNG-free drinking, 2% sodium salicylate and 20 mmol sodium deoxycholate was better than other four modeling methods. For C57 mice, it was also found that simple chemical drug mutagenesis and Helicobacter pylori replication method both could successfully establish CAG models. No matter from pathological observation, relative expression of anti-inflammatory factors and analysis of plasma biochemical parameters, the effects of combination of the two methods was better. Conclusion:The CAG mouse model established by MNNG-free drinking, 2% sodium salicylate and 20 mmol sodium deoxycholate can provide a certain reference for the establishment and application of mouse model in CAG experiments in the future for pharmacological research.

Objective:To explore the serotype distribution and drug resistance of Shigella in stool samples of children under five years old with diarrhea from 2008 to 2017 in Sui County, Henan Province. Methods:A total of 4 721 stool samples of children under five years old with diarrhea were collected from Doufuyuan Clinic of Sui County during 2008 to 2017, and Shigella strains were isolated through bacterial culture. The slide agglutination test was used for serotyping of Shigella strains. Two hundred of seventy-one Shigella strains were selected in proportion, and multiple gradient polymerase chain reaction was used to detect virulence genes and Kirby-Bauer agar method was used for drug sensitivity. Trend chi square test was used to analyze the annual trend of drug resistance. Results:The detection rate of Shigella strains in 4 721 fecal samples was 20.69% (977/4 721). A total of 977 Shigella strains were divided into 13 serotypes in two groups, including 77.79%(760/977) Shigella flexneri strains and 22.21%(217/977) Shigella sonnei strains.The top three serotypes detected alternately every year.The dominant gene pattern of Shigella flexneri was Shigella enterotoxin ( shET)-1+ , shET-2+ , invasion plasmid antigen H ( ipaH)+ , invasion-associated locus ( ial)+ , accounted for 84.04%(179/213) and that of Shigella sonnei was shET-1-, shET-2+ , ipaH+ , ial+ , accounted for 46.55%(27/58). The drug resistance rates of 271 Shigella strains to ampicillin, nalidixic acid and tetracycline were more than 90% and the strains were more sensitive to cefepime and ceftazidime.The drug resistance rates to cefotaxime, cefepime, ciprofloxacin, chloramphenicol and sulfamethoxazole/trimethoprim increased year by year, and all had statistically significant differences ( χ2=24.027, 7.232, 6.039, 4.764 and 6.809, respectively, all P< 0.05). There were 98.52%(267/271) strains resistant to more than three kinds of drugs. The resistance rates of Shigella flexneri to ciprofloxacin, norfloxacin, and chloramphenicol were higher than those of Shigella sonnei, and the resistance rates to gentamicin and sulfamethoxazole/trimethoprim were lower than those of Shigella sonnei. The differences were statistically significant ( χ2=31.866, 14.868, 83.036, 68.534 and 14.738, respectively, all P<0.01). Conclusions:The major serotypes of Shigella in children under five years old in Sui County are constantly changing from 2008 to 2017. The dominant gene patterns of different serotypes are different. Most isolated strains have multiple drug resistances, and different serotypes have different resistance profiles.

Objective To explore the optimal combination of parameters for the maximum spatial cluster size and maximum temporal cluster size of scan statistics. Methods The daily incidence data of hand-foot-and-mouth disease (HFMD) in Jingzhou in 2016 was collected as data source. The maximum spatial cluster sizes were set to 50%, 40%, 30%, 20%, and 10% of the population at risk. The maximum temporal cluster sizes were set to 7d, 14d, 30d, and 60d. A total of 20 parameter setting schemes were formed and spatial-temporal scanning was conducted one by one. The areas where the number of towns covered by the scanning area was less than 25 were selected, and the clustered epidemic of hand-foot-mouth disease can be detected at the same time in Xiejiaping Town of Songzi City and Sanzhou Town of Jianli County. The combination of large LLR and RR values was the optimal parameter setting. Results When the spatial windows were set to 20% of the population at risk, and the temporal windows were set to 30d, a total of 6 aggregation areas were detected. The number of covered townships was less than 25, and the clustered epidemic of Xiejiaping Township and Sanzhou Town were successfully detected. The LLR and RR values of the detected aggregation area were relatively large. This combination was the optimal parameter setting. Conclusion The combination of different parameters has a significant impact on the results of spatial-temporal scan statistics. It is recommended that parameters be optimized before applying this method.

Objective: This study was designed to evaluate the clinical value of seven combinedtumor-associated autoantibodies (7-TAAB) in the diagnosis of non-small cell lung cancer (NSCLC). Methods: This is a cross-sectional study. The 81 newly diagnosed patients with NSCLC were enrolled. 46 patients with benign pulmonary diseases (BLD) and 55 healthy subjects were selected as the BLD group and the healthy control (HC) group, respectively. ELISA was used to detect the concentration of seven TAABs of p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGE A1 and CAGE in the serum of the NSCLC and the other two groups. The levels of lung cancer tumor markers CEA, NSE, SCC and CYFRA21-1 in serum were also detected in all enrolled subjects. Kruskal-wallis test was used for comparison among the three groups, Mann-Whitney test was used to evaluate the differences between the two groups, and positivity rates were analyzed by using standard χ² tests and Fisher exact tests. The receiver operating characteristic (ROC) analyses were performed to evaluate the diagnostic efficacy of 7-TAAB or combination of 7-TAAB and traditional tumor markers. Results: The serological levels of six TAABs (p53, SOX2, GAGE7, GBU4-5, MAGE A1, and CAGE) in the NSCLC group were higher than that in the BLD group (p53: Z=-4.370, P=0.000; SOX2: Z=-4.412, P=0.000; GAGE7: Z=-4.250, P=0.001; GBU4-5: Z=-2.678, P=0.025; MAGE A1: Z=-4.504, P=0.002; CAGE: Z=-4.646, P=0.001) and the HC group (p53: Z=-3.543, P=0.000; SOX2: Z=-3.383, P=0.002; GAGE7: Z=-4.893, P=0.001; GBU4-5: Z=-3.381, P=0.025; MAGE A1: Z=-3.369, P=0.001; CAGE: Z=-2.981, P=0.002),respectively. The differences were statistically significant. The comparison of PGP9.5 in NSCLC group with that in the BLD group was statistically significant (Z=-2.871, P=0.044), with that in the HC group was no difference (Z=-2.280, P=0.05). None of the seven TAABs showed a significant difference between the BLD group and the HC group (p53: Z=-1.917, P=0.917; PGP9.5: Z=-1.228, P=0.966; SOX2: Z=-1.789, P=0.325; GAGE7: Z=-0.563, P=1.000; GBU4-5: Z=-0.315, P=0.985; MAGE A1: Z=-2.310, P=0.857; CAGE: Z=-2.822, P=0.703). According to the criteria of cut-off value, the detection value of individual TAAB was judged as negative or positive. The specificity of every single TAAB to NSCLC was ≥89%, but the sensitivity was ≤39.5%. Positive in any of the single TAAB was considered as a positive result of 7-TAAB, the positive rate of 7-TAAB in NSCLC subgroups with early stages (stageⅠand stageⅡ) was considered higher than that of traditional biomarkers (7-TAAB:52.94%, CEA: 23.53%, NSE: 8.82%, CYFRA21-1∶20.59%, SCC:14.71%), and 7-TAAB was more sensitive to NSCLC patients with poor prognosis, such as advanced stages (stageⅢand stageⅣ) and moderately-poorly differentiation. The AUC of 7-TAAB was 0.734, with a sensitivity of 66.67% and a specificity of 80.20%. In coordination with 7-TAAB, CEA, NSE, CYFRA21-1 and SCC, the AUC was 0.917, with a sensitivity of 87.70% and a specificity of 81.20%. Conclusions 7-TAAB, regarded as a panel of serological markers, is helpful in NSCLC diagnosis and shows broad application prospect. The detection rate of 7-TAAB in patients with early NSCLC is superior to that of traditional serum tumor markers, and the combination of 7-TAAB with CEA, NSE CYFRA21-1 and SCC could improve the diagnosis sensitivity of patients with NSCLC.

Objective To evaluate the effect of over-expression of phosphatase and tensin homolog does on chromosome ten (PTEN) in podocytes on kidney under high fat diet (HFD) in vivo and clarify the mechanism how PTEN regulates scavenger receptor A (SR-A) expression exposed to oxidized low density lipoprotein (ox-LDL) in podocytes in vitro.Methods The podocyte-specific PTEN knockin (PPKI) mice were fed with HFD to establish mouse model of lipid-induced renal injury.Mice were divided into four groups:ND+Ctrl group,ND+PPKI group,HFD+Ctrl group and HFD+PPKI group.After 24 weeks of dietary intervention,all mice were tested for clinical and biochemical parameters,including serum creatinine (Scr) as well as urine albumin excretion rate (UAER);renal lipid content was measured by oil red O staining and cholesterol quantitative analysis;the pathological changes of glomeruli were observed by PAS staining and electron microscope.Podocyte injury was induced by ox-LDL in vitro.Western blotting was used to detect the changes of SR-A expression induced by ox-LDL after YAP-siRNA interfering (si-YAP),as well as YAP phosphorylation induced by ox-LDL after interfering by PTEN-siRNA (si-PTEN) and PTEN phosphatase inhibitor (Bpv-PTEN),and overexpressing by recombinant adenovirus (ad-PTEN).Results Compared with ND+Ctrl group,HFD+ Ctrl group significantly aggravated the levels of Scr and UAER,the expression of SR-A in podocytes,renal lipid content,mesangial matrix expansion,effacement of podocyte foot processes,and incrassation of glomerular basement membrane (all P ＜ 0.05).Conversely,compared with HFD+Ctrl group,HFD+ PPKI group obviously alleviated the above lipid-induced renal damage (all P ＜ 0.05).In vitro,the expression of SR-A in podocytes was up-regulated when stimulated with ox-LDL (P ＜ 0.05),and the knockout of YAP significantly down-regulated the expression of SR-A induced by ox-LDL (P ＜ 0.05).Exposed to ox-LDL,the expression of p-YAP increased in podocytes (P ＜ 0.05);over-expression of PTEN inhibited p-YAP up-regulation induced by ox-LDL (P ＜ 0.05),while either knockdown of PTEN or inhibition of PTEN phosphatase activity displayed opposite effect (all P ＜ 0.05).Conclusions Over-expression of PTEN in podocytes protected the kidney against damage from HFD in vivo and PTEN might suppress SR-A mediated lipid uptake via dephosphorylating p-YAP to prevent podocyte injury from ox-LDL.