Gastric cancer is the fifth leading incidence and the third leading cause of death in the world. Gastric cancer patients in China are often in advanced stages and have a poor prognosis. Cancer progression depends not only on the cancer cells themselves, but also on the physiological state and composition of the tumor microenvironment in which they are located. Cancer-associated fibroblasts as the major cell type in the tumor microenvironment played an important role in cancer progression. This paper mainly expounds the origin and classification of cancer-associated fibroblasts, and its research progress on gastric cancer invasion and metastasis, growth, angiogenesis, matrix remodeling, immunomodulation and cancer suppression, and summarizes the relevant anti-tumor strategies by targeting cancer-associated fibroblasts in gastric cancer, to provide more information for use of cancer-associated fibroblasts in targeted therapy of gastric cancer.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is an etiology-unknown, non-specific, chronic inflammatory disorder of the intestinal tract with complex pathogenesis. Generally, patients with IBD present with repeated abdominal pain, diarrhea, mucus and blood in the stool, and even various systemic complications. More and more studies believe that it is a chronic inflammatory disease that occurs through the interaction of environment, genetics, intestinal flora, visceral sensitivity, and mental factors. In recent years, the incidence of IBD has been increasing year by year. Early-life exposure refers to the exposure from fetal period to childhood. Early-life adverse exposure (drug exposure, stress exposure, delivery methods, etc.) can have short-term or long-term effects on the intestines of infants, further affecting the physical and mental health of adolescents, adults, and even the elderly, this leads to long-term health effects. A number of studies have found that early-life adverse exposures are involved in the occurrence and progression of IBD. The occurrence of adverse exposure in early life can promote the occurrence and progression of IBD by changing the intestinal flora, immune function, epigenetic inheritance and visceral sensitivity. However, the mechanism by which early-life adverse exposure changes susceptibility to IBD remains unclear. In-depth study of the relationship between early-life adverse exposure and the occurrence of IBD can help prevent the occurrence of diseases at an early stage and reduce the burden of adulthood. This will greatly benefit the improvement of life and health and the rational use of medical resources. This article reviews the relationship between common early-life adverse exposure and the risk of IBD.

Objective To observe the effect of increasing brain cortical neuronal activity in mice on axon remyelination and motor function recovery after mild spinal cord contusion injury by chemical genetics technology (DREADDs). Methods 33 C57/BL male adult mice accepted stereotactic injection of adeno-associated virus with activated receptor [AAV-hM3D(Gq)-mCitrine] into the right cerebral cortex. Then all of the mice were randomly divided into three groups: sham group (n=11), SCI group (n=11) and activated group (n=11). SCI spinal cord injury model was established in SCI group and activation group. Two weeks later, activation group was intraperitoneally injected with 1 mg/(kg·d) clozapine N-oxide (CNO) to activate the electrical activity of cortical neurons. Sham group and SCI group were intraperitoneally injected with the same amount of normal saline once a day for 4 weeks. Animals were perfused at last, using immunofluorescence to observe the results of infection of virus, the expression of cellular Fos (cFos) within neurons and myelin basic protein (MBP) in dorsal corticospinal tract; transmission electron microscopy to show the result of axonal myelination; BMS scale and irregular horizontal ladders were used to evaluate the motor function of mice. Results Immunofluorescence microscopy confirmed successful transfection of virus into neurons at mice motor cortex, and there was no statistical significance of number of neurons infected by GFP labled adeno-associated virus between the three groups. Neuronal cFos fluorescence intensity at the transfection site in activated group was significantly higher than that in SCI group(P<0.001); MBP fluorescence intensity in the spinal cord injury center in activated group and sham group were significantly higher than that in SCI group (P<0.001). The G-ration value in activated group was apparently lower than that in SCI group (P<0.001). For the BMS score, there was no statistical significance between activated group and SCI group; the evaluation of irregular horizontal ladders found that after 2 weeks intraperitoneal injection, the error rate in activated group and SCI group decrease, and the error rate in activated group was significantly lower than that in SCI group (P<0.001); after 4 weeks intraperitoneal injection, the error rate in activated group and SCI group continued to decline, and the error rate in activated group was significantly lower than that in SCI group (P<0.001). Conclusion Using DREADDs strategies to improve the neuronal activity of cerebral cortical neurons can effectively promote the axon remyelination and the recovery of motor function after mild spinal cord contusion injury in mice.

Objective To investigate the gender difference of cognitive function in neonatal rats treated with sevoflurane. Methods Eighty two postnatal 7-day (P7) SD rats were randomly divided into control group and sevoflurane treated group, then divided into the following subgroups according to gender: female control group, male control group, female sevoflurane treated group, and male sevoflurane treated group. After inhaling air or 4% sevoflurane for 4 hours, the levels of serum cortisone and estradiol (E₂) were detected by ELISA, and the expressions of Ki-67 and neuronal core antigen (NeuN) in hippocampus were detected by immunohistochemistry. The open field experiment was performed with rat P21 and Morris water maze experiment was performed with rat P35 to explore the effects of sevoflurane exposure on the spatial cognitive function in different gender of rats. Results ELISA reveled that, compared with the control group, the serum cortisone level in sevoflurane treated group was significantly higher [(11.60±1.41) ng/ml vs. (7.93±1.58) ng/ml, P<0.05], while the serum E₂ level showed no significantly different [(35.0±8.25) pmol/L vs. (34.2±9.73) pmol/L, P>0.05]; and no significant difference existed in the levels of cortisone and E₂ between different genders (P>0.05). Immunohistochemistry showed that the number of Ki-67 and NeuN positive cells in hippocampal CA1 and dentate gyrus (DG) decreased significantly in sevoflurane treated group than those in control group(P<0.05). Also, no significant difference existed in the expression of hippocampal neurons between different genders (P>0.05).Morris water maze test showed that no significant difference was found among female rats (P>0.05); compared with male control group, the platform latency and moving distance of male sevoflurane treated group were significantly prolonged at the forth and fifth day of acquired training (P<0.01 or P<0.05). At the second day of counterpoint training, the platform latency and movement distance of rats in male sevoflurane treated group were significantly prolonged (P<0.05). In counterpoint exploration training, the platform latency of rats in male sevoflurane treated group was significantly prolonged (P<0.01), and the time spent in the target quadrant reduced significantly (P=0.031). Conclusions Sevoflurane treatment has a great influence on the serum cortisone level of postnatal rats, may inhibit the proliferation of hippocampal neural stem cells and neurogenesis. The learning ability of male rats decreased after adulthood, but no obvious effect on female rats.

Objective To investigate the effect and mechanism of B7-H4 expression on the prognosis of patients with gastric cancer. Methods The databases of Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN and Kaplan-Meier Plotter were used to analyze the expression of B7-H4 in gastric cancer tissues and its relationship with the prognosis of gastric cancer patients. Immunohistochemistry staining was performed to observe the expression of B7-H4 protein in gastric cancer tissues and analyze its correlation with clinicopathological characteristics, cell cycle regulatory proteins, microvessel density (MVD), stemness-related proteins, and PI3K/Akt/NF-κB signaling pathway proteins. Immunofluorescence and Western blotting were used to detect the expressions of B7-H4 and stemness-related proteins in gastric cancer cells. Oncomine database was employed to analyze the correlation between B7-H4 and the expressions of PI3K and Akt mRNA in gastric cancer tissues. Results The expression level of B7-H4 was higher in gastric cancer tissues than in normal tissues, and its expression was significantly related to tumor differentiation, pT staging, lymph node metastasis, distant metastasis and clinical staging (P<0.05), and indicated a poor prognosis in gastric cancer. The expression of B7-H4 was positively correlated with the expressions of cell cycle regulatory protein p16 (r=0.250, P<0.001) and stemness-related proteins LSD1 (r=0.331, P<0.001), SOX9 (r=0.176, P=0.018) and CD133 (r=0.434, P<0.001). The MVD was significantly higher in B7-H4 positive tissue than in B7-H4 negative tissue (P=0.019). Furthermore, B7-H4 was co-expressed with stemness-related proteins LSD1, SOX9, and CD133 in gastric cancer cell lines, and the expression of B7-H4 was positively correlated with the expressions of p-PI3K-p85 (r=0.269, P<0.001), p-Akt-Ser473 (r=0.282, P<0.01), p-Akt-Thr308 (r=0.214, P=0.005) and NF-κB p65 (r=0.157, P=0.034). The expression of B7-H4 in gastric cancer tissue was positively correlated with the expressions of PI3K mRNA (r=0.403, P<0.001) and Akt mRNA (r=0.351, P<0.001). Conclusion B7-H4 can promote gastric cancer progression and is closely related to poor prognosis, and the mechanism may be related to the regulation of gastric cancer stemness via PI3K/Akt/NF-κB.

Objective To explore the relationship of body mass index (BMI) to short-term and long-term clinical outcomes in patients with sepsis. Methods To retrospectively analyze 5571 clinical data of sepsis patients in the Beth Israel Deaconess Medical Center (Boston, MA, USA) registered from 2001 to 2012 in the Medical Information Market Intensive Care (MIMIC-Ⅲ) database. Cox proportional hazards regression model was used to assess the relationship between BMI and 30-day and 1-year mortality. Results Patients were divided into four groups according to BMI: underweight 336 cases (6.0%); normal weight 1752 cases (31.4%);overweight 1563 cases (28.1%); and obesity 1920 cases (34.5%). The 30-day mortality of the patients mentioned above were 42.3%, 36.6%, 32.2% and 29.6%, respectively (P<0.001), the 1-year mortality were 64.6%, 56.8%, 52.5% and 46.7%, respectively (P<0.001), and in-hospital mortality were 35.4%, 34.3%, 31.6% and 29.9%, respectively (P=0.018). The Cox proportional hazards regression analysis confirmed that, compared to the patients with normal weight, the 30-day and 1-year risk of death increased by 13% and 24%, respectively, in underweight patients; decreased by 17% and 14%, respectively, in overweight patients; and decreased by 22% and 21%, respectively, in obese patients. Conclusion The 30-day and 1-year survival rate is higher in overweight or obese sepsis patients than in those sepsis patients with underweight and normal weight after admission to the intensive care unit.

Objective To investigate the efficacy and safety of antithymocyte globulin (ATG) in the immune induction of deceased donor renal re-transplantation. Methods The clinical data of 20 renal re-transplantation patients treated with ATG from June 2017 to November 2020, were retrospectively studied. The safety was assessed with T lymphocyte subsets, pulmonary infection, and bone marrow suppression. The efficacy was assessed with acute rejection (AR) and delayed graft function (DGF). Results The study contained 15 males and 5 females. The average age was 45.7 (25-71) years; 6 patients were positive for prestored antibody and 14 negative antibody; 17 patients received a second transplantation, 3 did a third transplantation. T lymphocytes decreased more than 70% in average induced by ATG on the 1st day after surgery and gradually recovered to 50% of the amount on the 3rd day after surgery (P<0.01). Two weeks after surgery, the number of T lymphocytes recovered to the pretransplant level. NK cells showed a continuous decline (P<0.01). There were 5 patients (25.0%) who suffered AR, 1 patient (5.0%) did DGF, 7 patients(35.0%) presented with pulmonary infection, 5 patients (25.0%) presented with bone marrow suppression, and no ATG allergic reaction cases. The median follow-up period was 17.6 (6-53) months. During the follow-up period, 19 patients (95.0%) survived with allograft and 1 (5.0%) died. Conclusions ATG can significantly suppress the activation and proliferation of T cells, reduce the incidence of AR, and improve the short-term functional recovery of allograft with kidney re-transplantation. ATG induction does not increase the incidence of infection, and the clinical safety of ATG application is reliable.

Objective To analyze the clinical characteristics of myositis autoantibody detection in the diagnosis of interstitial lung disease (ILD), and explore the diagnosis and treatment of ILD with the help of clinical manifestations combined with antibody results. Methods Sixty-three patients of ILD accurately diagnosed with the help of myositis autoantibody detection were collected retrospectively and divided into three groups: anti-synthetase syndrome associated interstitial lung disease group(ASS-ILD group, n=22), polymyositis/dermatomyositis associated interstitial lung disease group (PM/DM-ILD group, n=18) and interstitial pneumonia with autoimmune features group (IPAF group, n=23). Their clinical characteristics, treatment and prognosis were analyzed and compared. Results The positive rates of Raynaud's phenomenon, joint symptoms, mechanic's hand and anti-ARS antibodies in ASS-ILD group were higher than those in IPAF group (P<0.0167). Compared with PM/DM-ILD group, ASS-ILD group had higher positive rates of Raynaud's phenomenon, cough, dyspnea, respiratory system symptoms as the first manifestation, anti-ARS antibodies but lower positive rates of fever, muscle symptoms, skin/muscle symptoms as the first manifestation (P<0.0167).Compared with IPAF group, PM/DM-ILD group had higher positive rates of muscle symptoms, skin symptoms, skin/muscle symptoms as the first manifestation, anti-ARS antibodies and anti-MDA5 antibody but lower positivity rates of respiratory system symptoms as the first manifestation (P<0.0167). In this study, chest radiological findings of all patients were mainly nonspecific interstitial pneumonia (NSIP). The abnormality in pulmonary functions manifested mainly as diffusion disturbance and restrictive ventilatory dysfunction. 87.3% of all patients were treated with glucocorticoid combined with immunosuppressants. After treatment, 81.0% of these patients showed improvement or stability, while 19.0% showed deterioration or death. The difference in prognosis between the three groups was not statistically significant (P>0.05). Conclusion The detection of myositis autoantibody should be paid more attention in ILD patients. Diagnosis, classification, treatment and prognosis evaluation of ILD could be made with the help of myositis autoantibodies.

Objective To investigate the distribution of inhaled allergens and analyze the related risk factors among allergic rhinitis (AR) patients in Zhangjiakou area. Methods Serum specific IgE antibody of inhaled allergens was detected in 532 suspected AR patients in the Department of Otolaryngology, Head and Neck Surgery of the First Affiliated Hospital of Hebei North University form April 2019 to August 2020. A total of 245 family members of outpatient and inpatient patients (except family members of respiratory department, dermatology department and otolaryngology department) in the same period were selected as the control group. AR questionnaire survey was conducted in the AR patients and control group, and the survey results were statistically analyzed. Results Of the 532 patients with suspected allergic rhinitis, 388 (72.9%) were positive for at least one allergen. The top three positivity rates of inhalation allergens were mugwort (89.9%), common ragweed (44.1%) and cat epithelium(21.4%) among the AR patients. In the single allergen positive patients, the mudwort has a much higher positive detection rate(86.0%). The positive degree of allergens was mainly distributed in class 2, class 3 and class 6 of mugwort, in class 1 of house dust and house dust mite, and in class 2 of other allergens. There were statistically significant differences in the allergen positive rate of AR patients in different months, regions and ages (P<0.05). The allergen positivity rate from July to September was significantly higher than that in other months, in bar-upper region was significantly higher than that in bar-lower region, and the positive rate of allergen gradually declined with the increase of age. The differences of allergens in ragweed, cat epithelium, house dust, house dust mite and streptomyces alternaria between genders of AR patients were statistically significant (P<0.05). Multivariate logistic analysis showed that previous allergies, parents with allergic rhinitis, history of asthma, secondhand smoke exposure, staying up late, age 3-24 years old were AR high-risk factors (OR>1), regular physical exercise was an effective protective factor for AR (OR<1). Conclusions The most common inhalation allergens in Zhangjiakou area are mugwort and common ragweed. The distribution of allergens is correlated with the month, region, and gender and age of the patients. Previous allergies, history of asthma, parents having allergic rhinitis, age and so on are risk factors for AR.

Objective To analyze the risk factors inducing hyperuricemia (HUA) in helicopter pilots and put forward the corresponding intervention measures. Methods A total of 190 male helicopter pilots, aged 20-50 years and with more than 100 hours of flight time, were recruited from April to October 2020 in a flight brigade. A self-designed questionnaire was used, by which the basic information of subjects were collected including eating habits, physical exercise, smoking and drinking, exposure to noise and vibration at work, mood, disease, work performance, sleep status, genetic factors, and so on. At the same time, 28 SPF grade 6-week-old male C57BL/6J mice were randomly divided into 7 groups (4 each): control group, noise group, noise + vitamin C (Vit C)group, noise + multivitamin (Multi Vit) group, noise + hyperbaric oxygen (HBO) group, noise + HBO + Vit C group, and noise +HBO + Multi Vit group. After continuous intervention for 7 days, Multiskan Ascent was used to detect the uric acid (UA) level in mice sera. Results Finally, 186 subjects, aged 22-50 years and with (1378±569) hours of flight time, were included in present study. Of whom 17 (9.14%) were self-reported with HUA (HUA group) and 169 (9.14%) were with normal uric acid (NUA group).No significant difference existed between the two groups in age, height, body mass index and the proportion of hyperglycemia. The proportions of hyperlipidemia and fatty liver were significantly higher in HUA group (17.6% and 29.4%, respectively) than those in NUA group (4.7% and 10.1%, respectively) with statistically significant difference (P<0.05). The scores of noise exposure and vibration exposure were significantly higher in HUA group [(22.942±3.960) and (16.351±3.552), respectively] than those in NUA group [(19.413±4.086) and (13.323±3.476), respectively] with statistically significant difference (P<0.05); there was no significant difference between the two groups (P>0.05) in the other 8 dimensions. Noise and vibration exposure were closely related to the occurrence of HUA. Among them, strong noise and long daily exposure, great influence on emotion, the poor effect and low use frequency of protective measures would significantly increase the risk of HUA; Long daily exposure and great influence on emotion of vibration would also increase the risk of HUA. Compared with the control group, the serum UA level in noise group increased significantly [(38.710±10.201) μmol/L vs. (191.935±9.542) μmol/L] with significant difference (P<0.05); The serum UA levels in noise + Vit C group [(127.419±5.349) μmol/L], noise + Multi Vit group [(111.290±7.030) μmol/L], noise + HBO group [(53.226±11.518) μmol/L], noise + HBO + Vit C group [(61.290±7.213) μmol/L] and noise + HBO + Multi Vit group[(69.355±13.968) μmol/L] were all lower significantly than that in noise group (P<0.05). The UA levels in noise + Vit C group, noise + Multi Vit group, noise + HBO + Vit C group and noise + HBO + Multi Vit group were still higher than that in control group(P<0.05), while there was no significant difference between noise + HBO group and control group (P>0.05). Conclusions HUA in helicopter pilots is related to noise and vibration exposure in working environment. Hyperbaric oxygen and dietary vitamin supplementation can effectively reduce the increase of serum uric acid level caused by noise exposure.