Gastric cancer is one of the most common malignant tumors in the world. Patients with gastric cancer are often treated by surgery, radiotherapy, chemotherapy or immunotherapy, but the clinical efficacy and prognosis are poor. As an important member of ADAMs family, a disintegrin and metalloprotease 17 (ADAM17) is significantly more highly expressed in gastric cancer than in adjacent tissues. It participates in the occurrence and development of gastric cancer by mediating EGFR, TNF-α, TGF-β/Smad, Notch and Wnt, FoxM1-ADAM17 and EGFR/ERK/SP1. The high expression of ADAM17 is also closely related to the poor prognosis of gastric cancer, suggesting that ADAM17 can be used as a biological index to predict the development and prognosis of gastric cancer and has great potential to become a new therapeutic target for gastric cancer. In this paper, the mechanism, treatment and prognosis of ADAM17 in the development of gastric cancer are reviewed, in order to provide new ideas for clinical diagnosis and treatment of gastric cancer.

This study aimed to investigate the efficacy and safety of apatinib plus programmed cell death protein 1 (PD-1) blockades for patients with metastatic colorectal cancer (CRC) who were refractory to the standard regimens. In this retrospective study, patients with metastatic CRC who received apatinib plus PD-1 blockades in clinical practice were included. The initial dosage of apatinib was 250 mg or 500 mg, and PD-1 blockades were comprised of camrelizumab, sintilimab and pembrolizumab. Efficacy and safety data were collected through the hospital’s electronic medical record system. From October 2018 to March 2022, a total of 43 patients with metastatic CRC were evaluated for efficacy and safety. The results showed an objective response rate of 25.6% (95% CI, 13.5%-41.2%) and a disease control rate of 72.1% (95% CI, 56.3%-84.7%). The median progression-free survival (PFS) of the cohort was 5.8 months (95% CI, 3.81-7.79), and the median overall survival (OS) was 10.3 months (95% CI, 5.75-14.85). The most common adverse reactions were fatigue (76.7%), hypertension (72.1%), diarrhea (62.8%), and hand-foot syndrome (51.2%).Multivariate Cox regression analysis revealed that Eastern Cooperative Oncology Group (ECOG) performance status and location of CRC (left or right-side) were independent factors to predict PFS of patients with metastatic CRC treated with the combination regimen. Consequently, the combination of apatinib and PD-1 blockades demonstrated potential efficacy and acceptable safety for patients with treatment-refractory metastatic CRC. This conclusion should be confirmed in prospective clinical trials subsequently.

So far, liver cancer is still a highly malignant tumor with a high incidence rate in China, and it seriously affects the life and health of Chinese people. Previous studies have shown that the development of liver cancer is associated with various factors such as virus, smoking, drinking, and nonalcoholic fatty liver disease. With continuous exploration, more and more studies have pointed out that nutritional factors and living environment are associated with the development and progression of liver cancer. Folic acid is a necessary nutrient for cell growth and reproduction, and its level in human body has an impact on the growth of tumor cells and is closely associated with liver cancer. This article reviews the research advances in the association between folic acid and liver cancer in recent years, so as to provide new reference and basis for the prevention and treatment of liver cancer.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has caused havoc across the entire world. Even though several COVID-19 vaccines are currently in distribution worldwide, with others in the pipeline, treatment modalities lag behind. Accordingly, researchers have been working hard to understand the nature of the virus, its mutant strains, and the pathogenesis of the disease in order to uncover possible drug targets and effective therapeutic agents. As the research continues, we now know the genome structure, epidemiological and clinical features, and pathogenic mechanism of SARS-CoV-2. Here, we summarized the potential therapeutic targets involved in the life cycle of the virus. On the basis of these targets, small-molecule prophylactic and therapeutic agents have been or are being developed for prevention and treatment of SARS-CoV-2 infection.

Antipyretic-analgesics are currently one of the most prescribed drugs in children.The clinical application of antipyretic-analgesics for children in our country still have irrational phenomenon, which affects the therapeutic effect and even poses hidden dangers to the safety of children.In this paper, suggestions were put forward from the indications, dosage form/route, dosage suitability, pathophysiological characteristics of children with individual differences and drug interactions in the symptomatic treatment of febrile children, so as to provide reference for the general pharmacists when conducting prescription review.

Reflux Esophagitis (RE) is a gastroesophageal motility disorder mainly caused by lower esophageal sphincter disorder caused by a variety of injury factors, acid-suppressing drugs such as Proton Pump Inhibitors (PPIs) are often used clinically. With the increase of PPIs-resistant reflux esophagitis cases, the demand for the pharmacokinetics and pharmacodynamics of acid-suppressing drugs is higher. In recent years, the emergence of a new class of acid-suppressing drugs, potassium-competitive acid blockers (P-CABs), has solved some clinical deficiencies of traditional proton pump inhibitors. It has the characteristics of effective, longer-lasting acid suppression, the inhibitory effect on gastric acid secretion is not affected by the state of gastric acid secretion, the individual differences in drug metabolism and efficacy are smaller, and the drug efficacy is not affected by food intake or not. It has obvious advantages in the efficacy of severe erosive esophagitis and PPIs-resistant severe erosive esophagitis, and is more cost-effective, and is expected to replace PPI as the first-line treatment for reflux esophagitis.

Objective To investigate effects of physical exercise (PE) on object recognition memory in adult rats of postnatal isoflurane (Iso) exposures.Methods One hundred and ten postnatal 7-day SD rats (P7) were randomly divided into four groups: normal control group (Naive), Naive+PE group (received physical exercise in P21: a treadmill exercise 30min each day, 5 times/week, for 6 weeks), Iso group (three times of 2-hour Iso exposure in P7, P9, and P11), and Iso+PE group (received PE in P21 after postnatal Iso exposures). In P67, behavioral testing was conducted including open field and object recognition task (ORT), recording the time (Discrimination Ratios, DR) that rats spent on exploring each object, evaluating effects of PE on object recognition memory.Results There was no significant difference in influence of PE on open field testing in all of the groups (P>0.05). Compared with Naive, there was no group difference in DR (P>0.05) for all groups, but the DR of Iso male rats was significantly higher than that of Naive female rats in P67, with significant difference (P=0.034). Compared with non-PE groups, whether or not postnatal Iso exposures, the DR of PE male groups was significantly higher (compared with Naive and Iso group:P67,P=0.050,P=0.017; P95,P=0.037,P=0.019); in female rats, the DR for ISO+PE group was lower than that of Iso group in P67 (P=0.036), but the DR of Naive+PE group was higher than that of Naive group in P95 (P=0.004). Compared with male rats, the DR of non-PE female rats was significantly higher in P67 (vis. Naive and Iso group:P=0.022,P=0.011); but in P95, the DR of non-Iso female groups was significantly higher than that of male groups (vis. Naive and Naive+PE:P=0.008,P=0.017).Conclusions There is no obvious impact of postnatal Iso exposures on object recognition memory of adult rats. These Results also indicate that postnatal PE could improve object recognition memory of non-spatial learning in adult rats. In addition, exercise benefits have gender differences.

Objective To investigate the potential effect of glucagon-like peptide-1 (GLP-1) analogue exendin-4 (Ex-4) on immune function of T lymphocytes via neuroendocrine modulation mechanism in mice following severe burns.Methods Male BALB/C mice were randomly (ramdam number) divided into thermal injury group (n =50) and sham-thermal group (n =30).The thermal injury model was made by exposing the back skin of 15％ total body surface area (TBSA) to 95 ℃ water for 7 seconds,while in sham-thermal model the mice were immersed in 37 ℃ water instead.The expression of GLP-1 receptor (GLP-1 R) was determined in sorted CM + T cells from normal mice by immunofluorescence method.In ex vivo experiment,the mice were sacrificed at 24 h post-bum,then the mononuclear cells (MNC) from spleen were separated from both groups and cultured in RMPI 1640 with 10％ FCS (fetal calf serum) in presence of ConA (concanavalin A,5 μg/mL).Cells were pretreated with catecholamine receptor antagonist propranolol (prop) for 1 hour,followed by consecutive dose of Ex-4 for another 48 h.In in vivo experiment,prop (30 mg/kg) was i.p.injected 30 minutes before thermal injury,then Ex-4 (2.4 nmol/kg) was injected i.p.immediately after scalding.Mice were sacrificed at 6 h and 24 h after thermal injury,then the serum and the spleens were collected.Results GLP-1R was expressed on splenic CD4 + T cells from normal micc.Ex-4 exerted no marked effect on the functions of T cells in terms of proliferation and IL-2 secretion at all doses examined ex vivo,which was not affected by pretreatment with prop.In vivo,T cell functions were suppressed by Ex-4 in thermal mice (P ＜ 0.05),but was restored by pretreatment with prop.Regardless of ex vivo or in vivo,Ex-4 could induce T cells switched to Th2 response (P ＜ 0.05).Moreover,the Th2 switch by Ex-4 was greatly potentiated by prop intervention in thermal mice in vivo other than ex vivo.Norepinephrine level was increased and epinephrine was decreased by Ex-4 in thermal mice.Both norepinephrine and epinephrine levels were obviously enhanced by pretreatment with prop.Conclusions Ex-4 can inhibit the proliferation and IL-2 secretion of splenic T lymphocytes through the sympathetic nervous system,however,it might induce Th2 switch from Th cells by acting directly on GLP-1R.

Objective To investigate effects of isoflurane anesthesia of different time interval on acute injury of brain function in neonatal rats with consistent total time of isoflurane anesthesia. Methods Seven-day neonatal Sprague-Dawley (SD) rats were randomly divided into normal control group (breathe the air), continuous anesthesia group (a single 6-hour exposure to 1.5% isoflurane), and intermittent anesthesia 1 day and 3 days groups (three times of 2-hour exposure to anesthesia with an interval of 1 day or 3 days), 12 rats in each group. The ratio of male to female was 5:7. They underwent the test of learning and memory in the radial arm maze (RAM) 21 days after birth, twice a day for 4 days. The number of entry into wrong arms, number of repeated errors, number of total arm entries, and time for completing the task were recorded for evaluation of effect of neonatal isoflurane on cognitive behavior in rats. Results ① Compared with normal control group, the percentage of number of errors > 3 in anesthesia of 3-day interval group was significantly decreased (33.3% vs. 46.9%, P < 0.05), the percentages of repeated errors > 0 and total arm entries > 8 were significantly increased (33.3% vs. 18.8%, 27.1% vs. 13.5%, both P < 0.05), but there were no statistically significant difference in the percentage of mistake number > 3 between continuous anesthesia group, interval anesthesia 1-day group and the normal control group (44.8%, 44.8% vs. 46.9%), the percentages of number of repeated mistake > 0 and total arm entries > 8 in above three groups were slightly increased as compared with those of normal control group (27.1%, 22.9% vs. 18.8%, 20.8%, 21.9% vs. 13.5%, all P > 0.05). No statistical differences in completing the task among normal control group, continuous anesthesia group, interval anesthesia 1 day and 3 days groups were found (minutes: 1.32±0.91, 1.54±1.05, 1.46±0.86, 1.38±0.79, all P > 0.05). ② It was found by gender analysis that the percentages number of repeated errors > 0 and total arm entries > 8 were significantly lower in female rats than those in the male rats only in normal control group (5.0% vs. 28.6%, P < 0.01; 5.0% vs. 19.6%, P < 0.05). There was no obvious gender difference in exposed groups. ③ Compared between groups of female rats, the percentages of repeated mistake > 0 in continuous anesthesia group, interval anesthesia 1 day and 3 days groups (25.0%, 25.0%, 30.0% vs. 5.0%, P < 0.05 or P < 0.01) and the percentage of total arm entries > 8 in interval anesthesia 1 day and 3 days groups were significantly higher than that of normal control group (22.5%, 25.0% vs. 5.0%, both P < 0.05). No significant difference about the RAM task in male rats of all the four groups was found. Conclusions Different time interval of neonatal isoflurane exposure may develop certain degree of acute brain injury in rats, characterized by cognitive function. Prolongation of the interval time significantly enhanced long-term memory in rats. Multiple neonatal exposures to isoflurane were associated with greater cognitive impairment than a single exposure. In addition, isoflurane can significantly increase cognitional functional disorder in the female, not in the male rats.