Objective To compare the pharmaceutics and drug interactions of noiiglutide injection,INS068 injection,HR17031 Injection,and noiiglutide+INS068 injection in healthy subjects Methods This was a single center,randomized,open-label,4-cycle,4-cohort trial.Healthy subjects were allocated to 4 groups randomly.HR17031(17 U/0.04 mg),INS068(17 U),noliglycopeptide(0.04 mg),and INS068(17 U)combined with noiiglutide(0.04 mg)were injected subcutaneously into the abdomenon on day 1,8,15 and 22 respectively.Venous blood was collected at different timing before and after administration,and the concentrations of noiiglutide in plasma and INS068 in serum were measured by HPLC-MS/MS method.Relevant pharmacokinetic parameters were calculated using the WinNonlin non compartment model.Results In HR17031,INS068,and INS068 combined with noiiglutide groups,the main pharmacokinetic parameters of INS068 in serum were calculated and listed as follows:Cmax were(19.50±4.06),(18.10±4.56)and(18.40±5.81)ng·mL-1,tmax was 12,10 and 8 h,t1/2 was(9.27±1.70),(11.00±2.81)and(11.0±3.18)h,AUC0-twere(505.00±62.20),(498.00±70.50)and(491.00±74.20)ng·mL-1·h.In HR17031,noiiglutide,and INS068 combined with noiiglutide groups,the main pharmacokinetic parameters of noiiglutide in plasma were calculated and listed as follows:Cmax were(3.61±0.82),(4.63±0.87)and(4.54±0.86)ng·mL-1,tmax was all 8.00 h,t1/2 was(10.50±1.61),(9.49±1.40)and(9.55±1.61)h,AUC0-twere(94.30±20.10),(106.00±20.20)and(105.00±19.00)ng·mL-1·h.Conclusion There was no significant difference in bioavailability of INS068 and noiiglutide in HR17031 compared with INS068 and noiiglutide whether combined or used alone.

Peripheral bacterial infections without impaired blood-brain barrier integrity have been attributed to the pathogenesis of Parkinson's disease (PD). Peripheral infection promotes innate immune training in microglia and exacerbates neuroinflammation. However, how changes in the peripheral environment mediate microglial training and exacerbation of infection-related PD is unknown. In this study, we demonstrate that GSDMD activation was enhanced in the spleen but not in the CNS of mice primed with low-dose LPS. GSDMD in peripheral myeloid cells promoted microglial immune training, thus exacerbating neuroinflammation and neurodegeneration during PD in an IL-1R-dependent manner. Furthermore, pharmacological inhibition of GSDMD alleviated the symptoms of PD in experimental PD models. Collectively, these findings demonstrate that GSDMD-induced pyroptosis in myeloid cells initiates neuroinflammation by regulating microglial training during infection-related PD. Based on these findings, GSDMD may serve as a therapeutic target for patients with PD.

Objective: To analyze HIV/AIDS surveillance data in men who have sex with men (MSM) aged from 15 to 24 years in Fuzhou and understand the HIV infection status in MSM and related factors. Methods: From 2016 to 2021, MSM aged 15-24 years who had oral or anal sex with men in the past 6 months were recruited through internet, and their demographic and behavioral characteristics, HIV antibody positive rate and risk factors were analyzed. Results: From 2016 to 2021, a total of 4 234 MSM aged 15-24 years were surveyed. The proportion of MSM from other provinces increased from 13.00% (85/654) to 23.42% (163/696) (trend χ²=60.23, P<0.001); and the proportion of MSM seeking male partners through internet increased from 93.27% (610/654) to 99.71% (694/696) (trend χ²=65.20, P<0.001); In the last anal sex in the past 6 months, the proportion of MSM using condom decreased from 88.16% (484/549) to 74.11% (415/560) (trend χ²=32.32, P<0.001); and in the past 6 months, the proportion of MSM using condom at each anal sex decreased from 65.76% (361/549) to 55.54% (311/560) (trend χ² =6.82, P<0.001); The proportion of MSM with HIV antibody testing increased from 5.66% (37/654) to 25.29% (176/696) (trend χ²=98.51, P<0.001). The cumulative HIV antibody positive rate in the MSM was 3.64% (154/4 234), and there was no significant difference in annual HIV antibody positive rate in the MSM (trend χ²=0.50, P=0.453). The HIV antibody positive rate in the MSM with education level of junior high school or below and the MSM living in Fuzhou for 1-2 years showed an upward trend (P<0.05). The results of multivariate logistic regression analysis showed that the risk for HIV infection in the MSM with education level of high school or technical secondary school was 0.54 times higher than that in those with education level of junior high school or below (95%CI: 0.30-0.99), and the risk for HIV infection in the MSM with education level of junior college or below was 0.29 times higher than that in those with education level of junior high school or below (95%CI: 0.17-0.51). The risk for HIV infection in the MSM who lived in Fuzhou for 1-2 years was 0.35 times higher than that in those who lived in Fuzhou for less than 1 year (95%CI: 0.16-0.74), the risk for HIV infection in the MSM who lived in Fuzhou for more than two years was 0.58 times higher than that in those who lived in Fuzhou for less than 1 year (95%CI: 0.37-0.91). The number of MSM using condoms at each anal sex was 0.18 times higher than that in the those never using condoms (95%CI: 0.08-0.42), and the number of the MSM who didn't suffered from sexually transmitted diseases was 0.25 times higher than that in those who suffered from sexually transmitted diseases (95%CI: 0.13-0.50). Conclusions: The MSM aged 15-24 years in Fuzhou have higher risk for HIV infection, and internet based intervention should be strengthened in adolescent MSM without permanent residence and with low education level.
Adolescent ; Male ; Humans ; Acquired Immunodeficiency Syndrome/epidemiology* ; HIV Infections/epidemiology* ; Homosexuality, Male ; Sexual and Gender Minorities ; Internet

OBJECTIVE: To investigate the endoscopic and pathological characteristics of gastric adenomatous polyps and to assess the potential risk factors for canceration of gastric adenomatous polyps. METHODS: The endoscopic and pathological characteristics of the patients with gastric adenomatous polyps from January 1, 2005 to December 31, 2019 were summarized retrospectively, and the risk factors of canceration were analyzed. RESULTS: A total of 125 patients with gastric adenomatous polyps were included, 51.20% of whom were females. The average age was (66.7±12.3) years. 64.80% of patients with gastric adenomatous polyps equal or more than 65 years old, and only 5.60% of the patients less than 45 years old. Adenomatous polyps were mostly distributed in the corpus and antrum with 40.80% and 32.80%, respectively. The majority of them were single (90.40%) and sessile (76.81%). 65.4% of adenomatous polyps were no more than 1.0 cm in diameter, and 23.20% of patients with adenomatous polyps were combined with hyperplastic polyps and/or fundus glandular polyps, and 1.60% had both pathological types of polyps. 58.62% (17/29) patients with hyperplastic polyps and/or fundus glandular polyps had multiple polyps. 1.60% (2/125) of the patients had gastric neuroendocrine tumor of G1 stage. Synchronous gastric cancer was detected in 13.60% (17/125) of the patients with adenomatous polyps, and the proportion of low-grade intraepithelial neoplasia was 18.40% (23/125). The main types of synchronous gastric cancer were progressive (70.59%) and undifferentiated (66.67%). Chronic atrophic gastritis with intestinal metaplasia was found in 52.80% of the patients, and autoimmune gastritis accounted for 11.20%. The positive rate of Helicobacter pylori was 21.60%. The canceration rate of gastric adenomatous polyps was 20.80%. The cancer was mainly differentiated, but there was sigmoid ring cell carcinoma as well. Diameter of >1.0 cm (OR=5.092, 95%CI: 1.447-17.923, P=0.011), uneven surface morphology and erosion (OR=13.749, 95%CI: 1.072-176.339, P=0.044) were independent risk factors of adenomatous polyps. CONCLUSION The synchronous gastric cancer is common and the canceration of gastric adenomatous polyps is high with diameter and surface morphology as independent risk factors. We should pay attention to the identification of the pathological types of polyps and the evaluation of the whole gastric mucosa during the endoscopic examination.
Adenomatous Polyps/epidemiology* ; Aged ; Female ; Gastric Mucosa ; Humans ; Middle Aged ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms/epidemiology*

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

Studies have shown that COVID-19 patients infected with SARS-CoV-2 have severe pulmonary inflammation and cytokine storm, so the treatment of cytokine storm is an important part of rescuing critically ill patients with COVID-19. As an important cause of death, the preclinical study of cytokine storm is essential, and related experiments in vivo and in vitro are also the only way to develop new drugs for COVID-19 in the future. This paper reviews the in vitro and in vivo experimental methods of cytokine storm research articles at home and abroad in recent years, including the establishment of animal models, cell evaluation methods, pharmacodynamic evaluation indicators, etc., in order to provide reference and guidance for the experimental design methods of cytokine storm.

Objective:To investigate the effect of 5.8 GHz radiofrequency (RF) radiation on learning and memory along with hippocampal synaptic plasticity in rats, in order to provide theoretical and experimental references for scientific evaluation of potential hazards of 5.8 GHz RF radiation.Methods:A total of 56 healthy adult male Sprague-Dawley rats were randomly divided into sham exposure group ( n=28) and RF exposure group ( n=28). RF groups were exposed to 5.8 GHz RF for 1 h each day in 15 d or 30 d continuously, and the whole-body absorption rate was 1.15 W/kg. The learning and memory ability of rats was tested by Morris water maze (MWM). The hippocampal structure of rats was observed by Nissl stain. The density of dendritic spines in CA1 region of hippocampus was detected by Golgi stain. The expression of synaptic related protein (PSD95, Synaptophysin) in hippocampus was detected by Western blot. The level of hippocampal neurotransmitters was detected by liquid chromatography-mass spectrometry. Results:In MWM experiments, at 15 d and 30 d after RF exposure, there was no statistically significant difference between sham group and RF group in the escape latency, frequency of crossing plateau, percentage of stay time in plateau quadrant and latency of first arrival to the plateau ( P>0.05). Besides, the structure and the number of neurons in the hippocampus, the density of apical and basal dendritic spines of pyramidal neurons in the CA1 region (apical: 5.10±0.20, 4.89±0.24, 4.58±0.27, 4.49±0.24, and basal: 4.81±0.17, 4.79±0.34, 4.20±0.27, 4.22±0.17, named as Sham 15 d group, RF 15 d group, Sham 30 d group, RF 30 d group, respectively), the expression of PSD95 and Synaptophysin and the level of multiple kinds of neurotransmitters in the hippocampus had no significant changes ( P>0.05). Conclusions:In this study, 5.8 GHz RF radiation has no significant influence on the spatial learning and memory ability along with the synaptic plasticity of hippocampal neurons of rats.

Objective: To investigate the expression pattern of tropomyosin 2(TPM2) in aorta of patients with aortic dissection and explore its clinical implication. Methods: Thirteen cases with acute type A aortic dissection(TAAD) diagnosed by transabdominal aortic angiography from 2015 in Tongji Hospital were included. During the operation, the aortic wall tissues of these patients were collected. Ten patients with heart transplantation were selected as control group, and normal aortic wall tissues were taken. The hematoxylin-eosin (HE) and Verhoeff's Van Gieson (EVG) staining were performed to observe the morphological changes of aorta. The mRNA expression level of TPM2 was measured by real-time fluorescent quantitative-PCR, and the protein levels of TPM2 were detected by Western blot and immunohistochemical staining. Image The J software was used to collect the optical density values of each point on the image, obtain the integrated optical density(IOD) value, and calculate the average density(%, IOD/area of the target distribution area). Results: HE and EVG staining revealed medial degeneration and broken elastic fiber in aorta of TAAD patients. The mRNA expression levels of TPM2 were significantly upregulated in aorta of TAAD patients as compared to the control group (P<0.05), so as the TPM2 protein expression levels ((9.73±1.20)% vs. (0.11±0.04)%, P<0.05). And TPM2 was mainly expressed in cytoplasm. Conclusion: The increased expression of TPM2 in TAAD patients hints that TPM2 might be involved in the pathogenesis of aortic dissection.
Aneurysm, Dissecting/genetics* ; Aorta ; Aortic Aneurysm, Thoracic/genetics* ; Gene Expression ; Humans ; RNA, Messenger ; Tropomyosin/metabolism*

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

A large number of cancer patients suffer from pain. Growing evidence suggested that pain might be a serious risk factor for cancer patients. The shared modulators and modulation pathways between neural system and tumor cells, such as various neurotransmitters and neurogenic cytokines, provide essential basis for the effect of pain on tumor. In this article, we reviewed some possible mechanism of this process from two aspects: the systematic regulation of central nervous system on endocrine and immunity, and the regional regulation of peripheral nerves on tumor cells. The aim of this review is to provide more innovative knowledge about pain and cancer and to emphasize the importance of anti-pain in the therapy of cancer.
Cancer Pain ; physiopathology ; Central Nervous System ; Humans ; Memory ; Neurotransmitter Agents ; Pain ; Peripheral Nerves