OBJECTIVE To compare the clinical efficacy and safety of camrelizumab combined with apatinib versus camrelizumab combined with chemotherapy as first-line treatment for advanced gastric cancer. METHODS A prospective randomized controlled trial was conducted， enrolling 99 patients with advanced gastric cancer admitted to the Chuzhou First People’s Hospital from March 2022 to December 2024. Patients were randomly assigned using a random number table： 48 received camrelizumab plus chemotherapy （control group）， and 51 received camrelizumab plus apatinib （observation group）. Clinical efficacy， serum tumor marker[carcinoembryonic antigen（CEA），carbohydrate antigen（CA）724，CA199，CA242]levels， immune function indicators（CD3+，CD4+，CD8+，CD4+/CD8+） levels before and after treatment， and adverse drug reaction （ADR） during treatment were compared between the 2 groups. RESULTS A total of 2 patients in the observation group and 3 in the control group were lost to follow-up. The disease control rate and objective response rate in the observation group were 95.92% and 85.71%， respectively， both significantly higher than 80.00% and 55.56% in the control group （P＜0.05）. The median progression-free survival was 9.61 months in the observation group， significantly longer than 6.72 months in the control group （P＝0.011）. Before treatment， there was no statistically significant difference in the levels of serum tumor markers and immune function indicators between the 2 groups （P＞0.05）. After treatment， the levels of CEA， CA724， CA199 and CA242 in 2 groups were significantly lower than before treatment， while the levels of CD3⁺， CD4⁺ and CD4 ⁺/CD8 ⁺ were significantly higher than before treatment， with greater improvements in the observation group （all P＜0.05）. The overall incidences of ADR and severe ADR showed no statistically significant difference between the 2 groups （P＞0.05）. CONCLUSIONS Camrelizumab combined with apatinib as first-line therapy for advanced gastric cancer may offer advantages over camrelizumab plus chemotherapy in terms of clinical efficacy and immune function improvement of patients， with an acceptable safety profile.

Objective To investigate the protective effect of wogonin on acute kidney injury(AKI)induced by li-popolysaccharide(LPS).Methods The model of septic-induced AKI was established on male C57BL/6J mice by a single intraperitoneal injection of LPS and normal C57BL/6J mice were used as normal control group.Twenty-four male C57BL/6 mice were randomly divided into 4 groups(6 mice in each group):normal control group(NC),normal control+wogonin(NC+WOG 12.5 mg/kg),LPS model group(LPS 10 mg/kg),LPS model+wogonin(LPS 10 mg/kg+WOG 12.5 mg/kg).After LPS intervention for 24 h,serum samples were collected to detect blood creatinine(CRE)and urea nitrogen(BUN)levels.HE staining and PAS staining were performed to observe the degree of renal pathological injury.Immunohistochemistry was performed to detect the degree of expression of inflammatory markers interleukin(IL)-1 β,IL-6 and tumor necrosis factor(TNF)-α in renal tissues.PCR was performed to detect the expression of KIM-1 and NGAL in renal tissues.Western blot was performed to detect the changes in protein expression of NF-κB signaling pathway subunits P65 and PP65 in renal tissues.Results Com-pared with NC group,CRE and BUN levels in LPS group increased(FCRE=60.90,P＜0.001,FBUN=82.13,P＜0.001);compared with LPS group,these indexes decreased in LPS+WOG group(P＜0.001).PCR test re-sults showed that compared with the NC group,the expression of KIM-1 and NGAL mRNA was significantly in-creased in LPS group(FKIM-1=146.3,P＜0.001,FNGAL=161.2,P＜0.001).In contrast,KIM-1 and NGAL mR-NA expression was decreased in the LPS+WOG group(P＜0.01).Renal histopathological examination showed that compared with the NC group,renal tissues of mice had renal tubular dilatation and inflammatory cell infiltration in LPS group;compared with LPS group,the number of tubular dilatation reduced and inflammatory cell infiltration was reduced in LPS+WOG group(FHE=721.4,P＜0.001;FPAS=518.9,P＜0.001).Immunohistochemical staining showed that the expression of IL-1 β,IL-6 and TNF-α was significantly increased in the LPS group;com-pared with the LPS groups(FIL-1β=114.6,FIL-6=108.9,FTNF α=251.6,all P＜0.001),these indexes de-creased in LPS+WOG group(all P＜0.01).Further studies using Western blot showed that the NF-κB signaling pathway of LPS-treated mice had been activated and produced a hyperphosphorylated state in comparison to the NC group(FPP65=13.02,P＜0.01),yet this pathway in the LPS+WOG group showed the opposite effect,namely attenuated activity and reduced phosphorylation when the control was LPS(P＜0.01).Conclusion WOG effec-tively blocked the NF-κB signaling pathway in the LPS-induced acute kidney injury model mice,thereby attenua-ting the inflammatory response and tissue damage in the kidneys of LPS-induced acute kidney injury mice.

Objective:Using the established epilepsy patient database to validate the efficacy of the web-based epilepsy diagnosis and anti-seizure medications (ASM) selection tool, EpiPick, for domestic epilepsy patients.Methods:The retrospective collection of clinical data was conducted on patients aged 10 and above who were diagnosed with epilepsy at the Comprehensive Epilepsy Center of the First Affiliated Hospital of Kunming Medical University from January 2017 to December 2020, with regular follow-up and complete information. According to the first ASM recommended by the EpiPick tool and whether they are consistent with the actual ASM used by patients, patients were divided into EpiPick group and clinical group to verify the effectiveness of the EpiPick tool in selecting ASM. The drug retention rate, Engel score, and cumulative probability of no consecutive episodes within 30 months after using the first ASM were compared between the 2 groups, and Kaplan-Meier survival curves were drawn. Finally, the diagnostic results provided by the EpiPick tool were compared with the actual types of epileptic seizures diagnosed clinically, and consistency tests were performed.Results:A total of 364 epilepsy patients were included, including 237 in the EpiPick group and 127 in the clinical group. The ASM retention rates of patients in the EpiPick group and clinical group were 67.9%(161/237) and 56.7%(72/127), respectively, with statistically significant differences (χ2=4.534, P=0.039). Grades Ⅰ, Ⅱ, Ⅲ and Ⅳ according to the Engel scores in the EpiPick group patients who took the first ASM after diagnosis accounted for 47.3%(112/237), 14.8%(35/237), 12.7%(30/237), and 25.3%(60/237), respectively, compared to the clinical group of 32.3%(41/127), 11.8%(15/127), 11.0%(14/127), and 44.9%(57/127), respectively. There was a statistically significant difference in Engel scores between the 2 groups (χ2=14.968, P=0.002). The cumulative seizure-free rates in the EpiPick group at the 1st, 6th, 12th, 30th month and above after starting the first ASM were 73.8%, 61.2%, 53.2%, and 50.6%, respectively, which in the clinical group were 52.0%, 44.1%, 40.2%, and 33.5%, respectively. The logrank test showed a statistically significant difference in the cumulative probability of consecutive seizure freedom between the 2 groups ( HR=0.644 ,95% CI 0.476-0.871 ,P<0.001). After grouping by seizure type [focal seizures (196 cases) and generalized seizures (168 cases)], the cumulative seizure-free rates at the 1st, 6th, 12th, 30th month and above after starting ASM were significantly higher in the EpiPick group than in the clinical group (comparison between the 2 groups in patients with focal seizures: HR=0.654, 95%CI 0.443-0.964, P=0.004; comparison between the 2 groups in patients with generalised seizures: HR=0.586, 95%CI 0.361-0.954, P=0.014). Among 364 patients, 293 cases were clinically diagnosed with seizure classification consistent with the classification results of EpiPick tool. Agreement between the algorithm and the experts in classifying generalized seizures was 83.9%(104/124), which in classifying focal seizures was 78.8%(189/240; Kappa=0.591, P<0.001). Conclusion:Web-based EpiPick tool is suitable to be used to select the first ASM, and is portable for Chinese non-epilepsy specialists to choose ASM for epilepsy patients.

OBJECTIVE To investigate the effect of raw and wine-processed Schisandra chinensis on neuro-immune-endocrine network in insomnia mice and its mechanism. METHODS Fifty mice were randomly divided into blank group， model group， diazepam group， raw S. chinensis group and wine-processed S. chinensis group， with 10 mice in each group. Except for blank group， the mice in the other groups were intraperitoneally injected with thyroxine solution to establish mice model of insomnia； at the end of each day’s modeling， the corresponding doses of diazepam，raw and wine-processed S. chinensis were given by gavage. The blank group and model group were given constant volume of normal saline. The general state of the mice was observed and recorded， and the total activity distance and upright times of the mice were detected； the EEG and EMG signals of mice were recorded， and the time ratio of sleep wake time （wake）， non-rapid eye movement （NREM） and rapid eye movement （REM） was analyzed； the contents of neurotransmitters [γ-aminobutyric acid （GABA）， 5-hydroxytryptamine （5-HT）， dopamine （DA）， norepinephrine （NE）， cortisol （CORT）] in brain suprachiasmatic nucleus （SCN） were detected； and the expressions of tumor necrosis factor α （TNF-α） and interleukin 1β （IL-1β） were detected； the mRNA expressions of clock gene Bmal1， circadian clock gene Clock and cycle gene Per2 were all detected. RESULTS Compared with the blank group， the mental state of the model group mice was relatively depressed， the amount of food and water increased， the body mass decreased， the hair was rough and shiny， and the circadian rhythm was irregular； the total activity distance and upright times decreased significantly； the time ratio of wake increased significantly， while the time ratios of REM and NREM decreased significantly； the content of 5- HT in brain SCN decreased significantly， while the content of NE， DA and CORT increased significantly； the fluorescence intensity of IL-1β and TNF-α was significantly increased； the relative expression level of Bmal1 and Clock mRNA was significantly increased， while the relative expression level of Per2 mRNA was significantly decreased （P＜0.05 or P＜0.01）. Compared with the model group， the general state of mice in diazepam group， raw S. chinensis group and wine-processed S. chinensis group was improved obviously， and most of the above index levels were significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS Raw and wine-processed S. chinensis have a certain therapeutic effect on insomnia mice， the mechanism of which may be related to the regulation of neuro-endocrine-immune system related biological indicators in insomnia mice.

Objective : To investigate the expression of Ca2 + -independent phospholipase A2 β (iPLA2 β) in human renal tubular epithelial cells (HK-2) induced by high glucose(HG) ，the relationship between iPLA2 β and ferroptosis and the protective mechanism of HG treated HK-2 cells． Methods: The HK-2 cells were treated with 30 mmol /L glucose，the overexpression model was constructed by transfection of iPLA2 β plasmid．Ferrostatin-1 ( Fer1) (an inhibitor of ferroptosis) and erastin (an activator of ferroptosis) were used as controls．After 36 hours of intervention，the kit detected the levels of superoxide (SOD) ，malonaldehyde(MDA) and iron in HK-2 cells．DCF immunofluorescence was used to detect intracellular reactive oxygen species ( ROS) ．The expression of ACSL4， GPX4，LPCAT3，TFR1 in HK-2 cells were measured by Western blot. Results : The expression of iPLA2 β downregulated in HG-induced injury of HK-2 cells．The levels of ROS and MDA in HK-2 cells increased，while the levels of GSH and SOD decreased．The expression of ACSL4，LPCAT3 and TFR1 decreased，and the expression of GPX4 increased in HK-2 cells．However，these indexes were improved after Fer-1 intervention．iPLA2 β overexpression could reduce the injury of HK-2 cells via attenuation of KIM-1． Further research revealed that iPLA2 β overexpression inhibited oxidative stress and ferroptosis in HK-2 cells injury induced by high glucose．Meanwhile， the improvement effect of iPLA2 β on HG-induced HK-2 cells damage could be eliminated by erastin． Conclusion iPLA2 β prevents HG-induced injury of HK-2 cells via regulating ferroptosis.

Abstract: To investigate the role and mechanism of macrophage-to-myofibroblast transition(MMT) induced by exosomes from high glucose-treated renal tubular epithelial cells. Methods: Human renal tubular epithelial cells(HK2) were divided into glucose control group(5.5 mmol/L D-glucose) and high glucose group(30.0 mmol/L D-glucose) and cultured for 48 hours. The supernatant was collected by ultracentrifugation and identified by transmission electron microscopy and Western blot. PKH67 labelled exosomes were used to stimulate THP-1 macrophages. Laser scanning confocal microscopy was used to observe the phagocytosis process. The expression of inducible nitric oxide synthase(iNOS), α-SMA and CD206 was detected by flow cytometry and Western blot to determine the best concentration and time point. Laser scanning confocal microscopy was used to detect the fluorescence co-expression of rabbit polyclonal to mannose receptor(CD206), α-smooth muscle actin(α-SMA), collage type-Ⅳ(Col-IV) and fibronectin(FN). The expression of tumor growth factor-beta 1(TGF-β1), interleukin(IL)-6,IL-10 was separately detected by real-time quantitative PCR(qRT-PCR) and enzyme-linked immunosorbent assay(ELISA). The expression of TGF-β1, mothers against decapentaplegic homolog 3(Smad3), phosphorylated-smad 3(p-Smad3) in THP-1 macrophages was detected by Western blot. Results: The expression of cluster of differentiation 63(CD63)and tumor susceptibility gene 101 protein(TSG101)was positive, while the Calnexin protein was negative in the supernatant, confirming that the specimen was exosomes with high purity. THP-1 macrophages could internalize each group of exosomes. 40 mg/L exosomes for 96 hours were the best experimental condition. After being stimulated by high-glucose-exosomes, the percentage of M1 macrophages would climax in 24 hours, and the rate of M2 macrophages would climax in 96 hours. Immunofluorescence staining showed that exosomes released by HG-treated HK2 induced CD206, α-SMA, Col-IV and FN accumulation in cultured THP-1 macrophages. Compared with normal-glucose-exosomes, high-glucose-exosomes increased the expression of TGF-β1, IL-10 in M2 macrophages and decreased the expression of IL-6(allP<0.05). Moreover, TGF-β1 and p-Smad3 proteins expression also increased significantly(allP<0.05). Conclusion Exosomes secreted by renal tubular epithelial cells in high glucose environment can induce M2 macrophages transdifferentiate into myofibroblasts, and its mechanism may be related to activation of TGF-β1/Smad3 signal pathway.

Chronic liver diseases can progress to liver fibrosis and cirrhosis and may lead to portal hypertension and even hepatocellular carcinoma. In recent years, more and more studies have shown that statins can improve liver histology, delay progression to liver fibrosis, and reduce the risk of decompensation and hepatocellular carcinoma in patients with nonalcoholic fatty liver disease. This article introduces the advances in the application of statins in patients with chronic liver diseases, so as to provide a basis for the prevention and treatment of chronic liver diseases.

Objective:To master the iodine nutritional level of children aged 8-10 and pregnant women in non-iodine excess areas in Hebei Province, and provide scientific basis and targeted prevention and treatment strategies for prevention and treatment of iodine deficiency disorders.Methods:Iodine nutrition analysis was conducted in 162 counties (cities and districts, hereinafter referred to as counties) of Hebei Province in 2018. Each monitoring county was divided into 5 sampling areas according to east, west, south, north and middle locations. One township/street was randomly selected in each area, 1 primary school was selected in each township/street, and 40 non-boarding students aged 8-10 were selected from each primary school. In each monitoring county, 20 pregnant women were selected from each of the 5 townships/streets. Both children and pregnant women were collected samples for salt and urinary iodine (with a random urine sample) detection. The iodine content of salt was tested using the "General Test Method for Salt Industry-Determination of Iodine" (GB/T 13025.7-2012), and Sichuan salt and other fortified edible salt used the arbitration method. The urinary iodine content was tested using the "Arsenic-Cerium Catalytic Spectrophotometric Determination of Iodine in Urine" (WS/T 107-2006).Results:A total of 31 883 samples of edible salt were collected from children's homes in 162 counties, among which 28 539 were iodized salt, 26 456 were qualified iodized salt, the iodized salt coverage rate was 88.36% (after population standardization), and the qualified iodized salt consumption rate was 81.03% (after population standardization). A total of 31 883 urine samples were collected from children, with the median urinary iodine of 193.13 μg/L. There was one county with a median urinary iodine < 100 μg/L, and the median urinary iodine in 150 counties was 100-299 μg/L. A total of 15 572 salt samples of pregnant women were collected, among which the iodized salt samples were 14 260, the qualified iodized salt samples were 13 363, the iodized salt coverage rate was 90.10% (after population standardization), and the qualified iodized salt consumption rate was 83.54% (after population standardization). A total of 15 569 pregnant women were collected urine samples, the median urinary iodine was 164.86 μg/L, and the number of counties with a median urinary iodine < 150 μg/L was 67.Conclusions:Iodine nutrition of children and pregnant women is appropriate at the provincial level, but children and pregnant women in some counties are at risk of iodine deficiency. In the future, the prevention and treatment of iodine deficiency disorders should focus on the iodine nutrition monitoring of the special needs.

Insomnia has become a common central nervous system disease. At present, the pathogenesis of insomnia is not clear. Animal models can help us understand the pathogenesis of the disease and can be used in transformational medicine. Therefore, it is very necessary to establish an appropriate model of insomnia. Clinical data show that insomnia patients with high levels of thyroxine and often accompanied by cardiovascular problems, a common mechanism underlying all of these physiological disruptions is the sympathetic nervous system. Combined with the characteristics of chronic onset of clinical insomnia, an insomnia model induced by long-term intraperitoneal injection of thyroid hormone has been created in our laboratory. In this paper, the insomnia-like state of the model was evaluated based on three validity criteria. Face validity has been demonstrated in metabolism, the Morris water maze, electrocardiogram (ECG) and electroencephalogram (EEG). Structure validity has been proved by the results of targeted metabolomics. After treatment with diazepam, a commonly used clinical anti-insomnia drug, the above physiological and pathological disorders were reversed. The results of comprehensive analysis show that the established thyrotoxicosis-associated insomnia model meets the validity requirement to establish an appropriate animal model of insomnia. The model presented in this article might help to study pathogenetic mechanisms of clinical insomnia, as well as to test promising methods of insomnia treatment.

Chronic kidney disease (CKD) is a common chronic disease, often accompanied by cognitive impairment (CI), which can progress to dementia. CKD-induced cognitive impairment (CKD-CI) seriously affects the patient's quality of life and disease self-management. From the perspective of kidney-brain axis, this article elaborates on the damage of vascular endothelial function, oxidative stress, endoplasmic reticulum stress, and inflammation caused by brain nerve damage, brain structure and function changes, cerebral hemodynamic imbalance, brain metabolic disorders and renal replacement therapy affect cognition mechanisms from pathophysiological, neuroimmunological and neuroimaging. This is a review of recent advance in the mechanism of cognitive impairment in CKD.