Objective To investigate the therapeutic effect of cnithol on acute pancreatitis(AP)rats and its regulatory mechanism on phosphoinositol 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods SPF-grade SD male rats were randomly divided into control group,model group(50 μg·kg-1 hyranin+10 mg·kg-1 LPS),positive control group(2 mg·kg-1 dexamethasone),experimental-L group(20 mg·kg-1 osthol)and experimental-H group(40 mg·kg-1 osthol),experimental-H+740Y-P group(40 mg·kg-1 osthol+2 mg·kg-1 PI3K activator 740Y-P),15 mice in each group.The activities of amylase and lipase in serum of rats were detected by automatic biochemical analyzer 24 h after the last administration.The levels of inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in serum,the content of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)in pancreas were detected by enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin(HE)staining was used to observe the pathological changes of pancreatic tissue and score the pathological damage.Western blot was used to detect the expression of PI3K/Akt pathway related proteins in rat pancreas.Results The activities of serum amylase in control group,model group,positive control group,experimental-H group and experimental-H+740Y-P group were(135.67±12.89),(1 027.84±32.16),(174.31±15.27),(186.70±17.39)and(835.92±28.78)U·mL-1,respectively;the contents of TNF-α were(35.69±3.10),(223.54±15.23),(48.76±4.25),(52.31±4.68)and(208.46±13.65)pg·mL-1,respectively;the contents of MDA were(2.15±0.14),(6.37±0.42),(2.78±0.17),(2.81±0.15)and(5.96±0.36)nmol·mg-1,respectively;the histopathological injury scores were 1.12±0.07,10.23±0.38,3.14±0.21,3.25±0.23 and 9.68±0.40,respectively;p-PI3K/PI3K ratios were 0.82±0.05,1.96±0.15,1.07±0.06,1.10±0.07 and 1.69±0.14,respectively.The above indexes were compared with the control group in the model group,the positive control group,experimental-H group and the model group,and the above indexes of experimental-H+740Y-P group and experimental-H group,and the differences were statistically significant(all P＜0.05).Conclusion Gossetin can play a therapeutic role in AP,and its mechanism may be related to the inhibition of PI3K/Akt signaling pathway.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

BACKGROUND: Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations. METHODS: In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs' safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs' relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively. RESULTS: 81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count. CONCLUSIONS In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.

Objective: To investigate the efficacy of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy (HIPEC-IP-IV) in the treatment of peritoneal metastases from gastric cancer (GCPM). Methods: This was a descriptive case series study. Indications for HIPEC-IP-IV treatment include: (1) pathologically confirmed gastric or esophagogastric junction adenocarcinoma; (2) age 20-85 years; (3) peritoneal metastases as the sole form of Stage IV disease, confirmed by computed tomography, laparoscopic exploration, ascites or peritoneal lavage fluid cytology; and (4) Eastern Cooperative Oncology Group performance status 0-1. Contraindications include: (1) routine blood tests, liver and renal function, and electrocardiogram showing no contraindications to chemotherapy; (2) no serious cardiopulmonary dysfunction; and (3) no intestinal obstruction or peritoneal adhesions. According to the above criteria, data of patients with GCPM who had undergone laparoscopic exploration and HIPEC from June 2015 to March 2021 in the Peking University Cancer Hospital Gastrointestinal Center were analyzed, after excluding those who had received antitumor medical or surgical treatment. Two weeks after laparoscopic exploration and HIPEC, the patients received intraperitoneal and systemic chemotherapy. They were evaluated every two to four cycles. Surgery was considered if the treatment was effective, as shown by achieving stable disease or a partial or complete response and negative cytology. The primary outcomes were surgical conversion rate, R0 resection rate, and overall survival. Results: Sixty-nine previously untreated patients with GCPM had undergone HIPEC-IP-IV, including 43 men and 26 women; with a median age of 59 (24-83) years. The median PCI was 10 (1-39). Thirteen patients (18.8%) underwent surgery after HIPEC-IP-IV, R0 being achieved in nine of them (13.0%). The median overall survival (OS) was 16.1 months. The median OS of patients with massive or moderate ascites and little or no ascites were 6.6 and 17.9 months, respectively (P<0.001). The median OS of patients who had undergone R0 surgery, non-R0 surgery, and no surgery were 32.8, 8.0, and 14.9 months, respectively (P=0.007). Conclusions: HIPEC-IP-IV is a feasible treatment protocol for GCPM. Patients with massive or moderate ascites have a poor prognosis. Candidates for surgery should be selected carefully from those in whom treatment has been effective and R0 should be aimed for.
Male ; Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Young Adult ; Adult ; Stomach Neoplasms/surgery* ; Peritoneal Neoplasms/secondary* ; Hyperthermic Intraperitoneal Chemotherapy ; Percutaneous Coronary Intervention ; Hyperthermia, Induced/methods* ; Combined Modality Therapy ; Laparoscopy/methods* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Perfusion ; Cytoreduction Surgical Procedures ; Survival Rate

To investigate two clusters of severe fever with thrombocytopenia syndrome virus (SFTSV) in Xinyang City, Henan Province, in 2022, and analyze their causes, transmission route, risk factors, and the characteristics of virus genetic variation. Case search and case investigation were carried out according to the case definition. Blood samples from cases, family members and neighbors and samples of biological vectors were collected for RT-PCR to detect SFTSV. The whole genome sequencing and bioinformatics analysis were performed on the collected positive samples. A total of two clustered outbreaks occurred, involving two initial cases and ten secondary cases, all of which were family recurrent cases. Among them, nine secondary cases had close contact with the blood of the initial case, and it was determined that close contact with blood was the main risk factor for the two clustered outbreaks. After genome sequencing analysis, we found that the SFTSV genotype in two cases was type A, which was closely related to previous endemic strains in Xinyang. The nucleotide sequence of the SFTSV in the case was highly homologous, with a total of nine amino acid mutation sites in the coding region. It was not ruled out that its mutation sites might have an impact on the outbreak of the epidemic.
Humans ; Severe Fever with Thrombocytopenia Syndrome/epidemiology* ; Bunyaviridae Infections/epidemiology* ; Thrombocytopenia/complications* ; Phlebovirus/genetics* ; Disease Outbreaks ; China/epidemiology*

To investigate two clusters of severe fever with thrombocytopenia syndrome virus (SFTSV) in Xinyang City, Henan Province, in 2022, and analyze their causes, transmission route, risk factors, and the characteristics of virus genetic variation. Case search and case investigation were carried out according to the case definition. Blood samples from cases, family members and neighbors and samples of biological vectors were collected for RT-PCR to detect SFTSV. The whole genome sequencing and bioinformatics analysis were performed on the collected positive samples. A total of two clustered outbreaks occurred, involving two initial cases and ten secondary cases, all of which were family recurrent cases. Among them, nine secondary cases had close contact with the blood of the initial case, and it was determined that close contact with blood was the main risk factor for the two clustered outbreaks. After genome sequencing analysis, we found that the SFTSV genotype in two cases was type A, which was closely related to previous endemic strains in Xinyang. The nucleotide sequence of the SFTSV in the case was highly homologous, with a total of nine amino acid mutation sites in the coding region. It was not ruled out that its mutation sites might have an impact on the outbreak of the epidemic.
Humans ; Severe Fever with Thrombocytopenia Syndrome/epidemiology* ; Bunyaviridae Infections/epidemiology* ; Thrombocytopenia/complications* ; Phlebovirus/genetics* ; Disease Outbreaks ; China/epidemiology*

Idiopathic pulmonary fibrosis （IPF） is a common， lethal interstitial lung disease characterized by airway remodeling， inflammation， alveolar destruction， and fibrosis. The mammalian target of rapamycin complex 1/4E binding protein 1 （mTORC1/4E-BP1） axis is closely related to the expression of collagen by fibroblasts， and its role in pulmonary fibrosis remains to be further elucidated. Traditional Chinese medicine （TCM） has shown promising efficacy in improving the lung function， exercise capacity， and quality of life in patients with IPF. The theory of "same treatment for different diseases" provides a TCM theoretical basis for the treatment of pulmonary fibrosis with Bupleuri Radix， while the research in western medicine has preliminarily shown that both the formulation and single herb as well as the active ingredients of Bupleuri Radix have good therapeutic effects on pulmonary fibrosis. Therefore， this review will elaborate on the role of the mTORC1/4E-BP1 axis in the pathomechanism of IPF， as well as the research results of the active components of Bupleuri Radix on the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin protein（PI3K/AKT/mTOR） pathway， so as to provide a reference for the treatment and drug development of IPF.

OBJECTIVE: To investigate the clinicopathological features and prognosis of fumarate hydratase deficient renal cell carcinoma (FH-RCC). METHODS: Immunohistochemical (IHC) staining was used to detect the expression of fumarate hydratase (FH) in tumor tissues of 109 different types of renal cell carcinoma (RCC) patients aged 60 years and younger from the Department of Urology of Peking University First Hospital from January 2013 to December 2019. The clinicopathological data and prognosis of FH-RCC were collected and analyzed. RESULTS: There were eleven patients with FH-negative expression. Seven were males and four females. The age of onset ranged 16-53 years (mean age: 36.7 years), and four female patients all had a history of uterine leiomyoma. Only one first-degree relative of one patient had renal cancer, and none of the patients had a history or family history of cutaneous leiomyomas. The diameter of the tumor was 2.1-12.0 cm (mean: 8.83 cm). Renal sinus or perirenal fat invasion was seen in nine cases, tumor thrombus in renal vein or inferior vena cava in six cases, lymph node metastasis in seven cases, adrenal gland invasion in four cases and splenic capsule invasion in one case. The cases were initially diagnosed as type Ⅱ papillary RCC (7/49, 14.3%), collecting duct carcinoma (2/9, 22.2%) and unclassified RCC (2/51, 3.9%). Tumor histopathology mostly showed a mixture of different structures, such as papillary, tubular cystic, solid, and so on. The most common histological structures were papillary (9/11, 81.8%) and tubular (8/11, 72.7%). Three cases had sarcomatoid areas. At least focal eosinophilic nucleolus (WHO/grades Ⅲ-Ⅳ) and perinuclear halo could be seen in all cases. Immunohistochemical (IHC) stains of most tumors were negative for CA9, CD10 and CK7. The results of fluorescence in situ hybridization (FISH) showed that there was no translocation or amplification of TFE3 gene in two cases with TFE3 IHC expression. All the patients were followed up for 11-82 months. Mean survival was 24 months. Five cases died of distant metastasis 9-31 months after operation (mean: 19 months), and five of the six patients alive had became metastatic. CONCLUSION Morphologically, FH-RCC overlaps with many types cell RCC. A mixture of papillary and tubular cystic arrangement is the most common growth pattern of FH-RCC. At least focally large and obvious eosinophilic nucleoli are an important histological feature of this tumor. The negative expression of FH can help to confirm the diagnosis. Young female RCC patients with uterine leiomyomas should be suspected of FH-RCC. Some FH-RCC cases lack clinical evidence. The suspicion raised by pathologists based on histological characteristics is often the key step to further genetic testing and the final diagnosis of the tumor.
Adolescent ; Adult ; Biomarkers, Tumor ; Carcinoma, Renal Cell/genetics* ; Female ; Fumarate Hydratase/genetics* ; Humans ; In Situ Hybridization, Fluorescence ; Kidney Neoplasms/genetics* ; Male ; Middle Aged ; Prognosis ; Young Adult

Dendritic cells (DCs) are the most powerful and professional antigen-presenting cells (APCs) known at present. They play vital roles in the initiation and regulation of immune responses in body. Therefore, DC-based vaccine delivery system has gradually become a hotspot of basic scientific research and clinical treatment. DCs can be loaded with whole-cell antigens, nucleic acids, peptides, proteins (such as neoantigens) and nanoparticles to induce specific cellular immune responses and humoral immune responses after antigen processing, presentation and targeting delivery in vivo for the prevention and treatment of various diseases including cancers and microorganism infections. Vaccine-based on this technique is called dendritic cell (DC) vaccines. Great process in DC vaccines has been achieved in recent years. Therefore, we reviewed the characteristics of DC, types of DC vaccines and their clinical research progress in this paper.

S100 calcium binding protein A9 (S100A9) is involved in a variety of biological processes such as inflammation and tumor cell migration and invasion regulation. The purpose of this study was to construct S100A9 gene-edited mice by using CRISPR/Cas9 technology, thereby providing an animal model for exploring the biological functions of this gene. According to the S100A9 gene sequence, the single-stranded small guide RNA (sgRNA) targeting exons 2 and 3 was transcribed in vitro, and a mixture of Cas9 mRNA and candidate sgRNA was injected into mouse fertilized eggs by microinjection. Early embryos were obtained and transferred to surrogate mice, and F
Animals ; Bronchoalveolar Lavage Fluid ; CRISPR-Cas Systems/genetics* ; Calgranulin B ; Disease Models, Animal ; Gene Knockout Techniques ; Gene Targeting ; Lung ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Ovalbumin ; Phenotype