OBJECTIVE To assess the safety profile of sintilimab in combination with chemotherapy for the treatment of cholangiocarcinoma. METHODS The data of patients with cholangiocarcinoma from January 1st， 2021 to December 31st， 2022 were collected and divided into control group （29 cases） and observation group （18 cases） based on different medication regimens. Patients in the control group were treated with Gemcitabine hydrochloride for injection+Cisplatin for injection or Oxaliplatin for injection， the observation group was treated with Sintilimab injection based on the control group. Patients in each group underwent blood routine， liver and kidney function， biochemical and other examinations before and after each treatment cycle to observe the occurrence of adverse drug reactions. The correlation of adverse drug reactions with drugs was evaluated with Naranjo’s scale. RESULTS The correlation between blood toxicity and drug use was deemed “probable” in both groups； however， the observation group exhibited a significantly higher score， indicating a stronger correlation. In the control group， hepatotoxic reactions were classified as “suspicious” whereas in the observation group， they were categorized as “probable”. The correlation of gastrointestinal symptoms between the two groups was considered “possible”. Systemic symptoms， skin toxicity， musculoskeletal toxicity， endocrine toxicity and renal toxicity were all classified as having a “suspicious” correlation with drug use. The total incidence of blood toxicity in the observation group was significantly higher than control group （P＝0.014）. There was no statistically significant difference in the total incidences of hepatotoxic， gastrointestinal symptoms， systemic symptoms， skin toxicity， musculoskeletal toxicity， endocrine toxicity， renal toxicity， or the incidence of grade 3 or higher blood toxicity， hepatotoxic between the two groups （P＞0.05）. For the patients experiencing adverse drug reactions， the symptoms were alleviated following drug discontinuation or symptomatic supportive treatment. No fatalities occurred during the treatment period. CONCLUSIONS Sintilimab combined with chemotherapy may significantly increase the risk of blood toxicity in patients with cholangiocarcinoma， especially thrombocytopenia， but the adverse reactions are within a controllable range， and the overall safety is good.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Aim To observe the effect of thalidomide on the learning and memory ability and hippocampal tissue proteome of Alzheimer's disease(AD)mice,to screen the differential proteins of thalidomide in preventing and treating AD,the pathways involved in regulation,and to explore its possible mechanism. Methods The experimental mice were randomly divided into blank control group,model group,and thalidomide high and low dose groups. The drugs were administered by gavage every day for 21 days. After the administration,Morris water maze test was used to evaluate the learning and memory abilities of the mice,HE staining and Nissl staining were used to observe the pathological tissue morphology of the mouse hippocampus,ELISA was employed to detect the mitochondrial respiratory chain enzyme complex in mouse brain,and the Label-free proteomics method was used to screen different groups of hippocampal proteome proteins. Results The results of the Morris water maze showed that compared with the model group,the escape latency time of the drug group was significantly reduced,and the number of crossing the platform significantly increased(P<0.05). Thalidomide administration could improve the morphological structure of neurons in hippocampus,and could increase the activity of the mitochondrial respiratory chain complex ,Ⅱ, and of the brain tissues of AD mice(P<0.05). A total of 4 378 differential proteins were identified,which had a significant regulatory effect on the expression of 580 proteins in hippocampus of AD mice(P<0.05). Energy metabolism may jointly participate in the regulation of neurodegeneration pathways-changes in pathways such as various diseases and Alzheimer's disease. Conclusions Thalidomide can significantly improve the learning and memory function of AD model mice induced by Aβ

Objective: To analyze the repetitive reporting of hepatitis B in Fujian province during 2016-2020, and provide evidence for the improvement of hepatitis B surveillance. Methods: The reporting cards from the China Information System for Disease Control and Prevention were collected and divided into repetitive reporting cards and non-repetitive reporting cards from the report cards collected according to the valid ID number on the cards, and the proportion of repetitive report cards and related factors were analyzed by using software SAS 9.4. Results: A total of 314 551 hepatitis B reporting cards were submitted in Fujian from 2016 to 2020, in which 90.93% (286 020/314 551) were included in the analysis. The repetitive reporting cards accounted for 10.48% (29 982/286 020). The annual proportion of the repetitive reporting cards from 2016 to 2020 was between 2.98% and 3.71%, showing an overall increasing trend year by year (Z=2.26, P=0.024). The proportions of the repetitive reporting cards in 1-5 years were 3.17%, 5.40%, 7.74%, 9.27% and 10.48%, respectively, showing an increase trend with year (Z=128.16, P<0.001). The proportions of the repetitive reporting cards in 10 areas of Fujian ranged from 5.44% to 13.48% with significant difference (χ²=2 050.41, P<0.001) and increased with the increase of reported incidence of hepatitis B (Z=26.92, P<0.001). There were significant differences in relationships between repetitive reporting proportion and sex, age and type of the cases between the areas with high incidence and low incidence of hepatitis B. Conclusions: The reported incidence of hepatitis B was seriously affected by the repetitive reporting in Fujian from 2016 to 2020. A cross-year and cross-area surveillance mechanism for hepatitis B should be established and targeted measures should be taken to strengthen the control of the repetitive reporting and improve the surveillance for hepatitis B.
China/epidemiology* ; Data Collection ; Hepatitis B/epidemiology* ; Humans ; Incidence ; Software

【Objective】 To investigate the effects of CSF-1 transport from dorsal root ganglion to spinal cord on activation of microglia in rats with neuropathic pain induced by vincristine. 【Methods】 A total of 54 male 10-12-week old SD rats with successful intrathecal catheterization, weighing 200-230 g, were divided into three groups according to the random number table method(n=18) : Control group(Control), Chemotherapy-induced Neuropathic Pain+intrathecal injection of IgG group(CINP), Chemotherapy-induced neuropathic pain+intrathecal injection of CSF-1 neutralizing antibody(CINP+anti). The animal model of CINP was established by intraperitoneal injection of vincristine 125 μg/kg on four alternate days. Mechanical allodynia and heat hyperalgesia were evaluated by MWT and TWL, respectively. The expression of CSF-1 and microglial marker Iba1 were detected by immunofluorescence chemistry and Western blotting. The mRNA expression of CSF-1 and Iba1 was measured by RT-PCR. The expression TNF-α, IL-6 and IL-1β were determined by ELISA. 【Results】 Compared with Control group, MWT and TWL in CINP group decreased significantly on the 3rd, 5th and 7th day after the first injection of vincristine(P<0.01), MWT and TWL in CINP+anti group increased significantly on the 5th and 7th day compared with CINP group(P<0.01). Compared with Control group, the protein and mRNA expression of CSF-1 in DRG, the mRNA expression of Iba1 in spinal cord, the protein expression of CSF-1 and Iba1 in spinal cord, the immunofluorescence intensity of CSF-1 in DRG and Iba1 in spinal cord , and the expression of TNF-α, IL-6 and IL-1β in spinal cord were significantly up-regulated in CINP group(P<0.01, P<0.001). Compared with CINP group, the protein expression of CSF-1 in DRG and spinal cord, the protein and mRNA expression of Iba1 in spinal cord, the immunofluorescence intensity of spinal Iba1 and CSF-1 in DRG, and the expression of TNF-α, IL-6 and IL-1β were obviously downregulated in CINP+anti group(P<0.05, P<0.01, P<0.001) . 【Conclusion】 The transport of CSF-1 from dorsal root ganglion to spinal cord is involved in the process of neuropathic pain induced by vincristine, and its mechanism may be related to the activation of microglia and inflammatory reaction in rat spinal cord.

This study aimed to further validate the prognostic role of fibrinogen in upper tract urothelial carcinoma (UTUC) in a large Chinese cohort. A total of 703 patients who underwent radical nephroureterectomy were retrospectively identified. Fibrinogen levels of ≥4.025 g l^-1 were defined as elevated. Logistic regression analysis was performed to determine the association between fibrinogen and adverse pathological features. Kaplan-Meier analysis and Cox regression models were used to assess the associations of fibrinogen with cancer-specific survival (CSS), disease recurrence-free survival (RFS), and overall survival (OS). Harrell c-index and decision curve analysis were used to assess the clinical utility of multivariate models. The median follow-up duration was 42 (range: 1-168) months. Logistic regression analysis revealed that elevated fibrinogen was associated with higher tumor stage and grade, lymph node involvement, lymphovascular invasion, sessile carcinoma, concomitant variant histology, and positive surgical margins (all P < 0.05). Multivariate Cox regression analysis demonstrated that elevated fibrinogen was independently associated with decreased CSS (hazard ratio [HR]: 2.33; P < 0.001), RFS (HR: 2.09; P < 0.001), and OS (HR: 2.09; P < 0.001). The predictive accuracies of the multivariate models were improved by 3.2%, 2.0%, and 2.8% for CSS, RFS, and OS, respectively, when fibrinogen was added. Decision curve analysis showed an added benefit for CSS prediction when fibrinogen was added to the model. Preoperative fibrinogen may be a strong independent predictor of worse oncologic outcomes in UTUC; therefore, it may be valuable to apply this marker to the current risk stratification in UTUC.
Aged ; Biomarkers, Tumor ; Carcinoma, Transitional Cell/surgery* ; China ; Disease-Free Survival ; Female ; Fibrinogen/analysis* ; Humans ; Male ; Middle Aged ; Nephroureterectomy ; Prognosis ; Retrospective Studies ; Survival Rate ; Urologic Neoplasms/surgery*

Objective To investigate the clinical value and surgical methods of pancreaticoduodenectomy (PD) combined with portal vein (PV)/superior mesenteric vein (SMV) resection and reconstruction in the treatment of pancreatic cancer with PV/SMV invaded by tumor.Methods The clinical data of 21 patients of pancreatic cancer with PV/SMV invaded by tumor (group A) and 62 patients of pancreatic head cancer without PV/SMV invaded by tumor (group B) in the same period were collected and analyzed retrospectively from Jan 2014 to Apr 2017.There were no distinct invasion of celiac artery (CA),hepatic common artery (HCA) and superior mesenteric artery (SMA) in two groups of pancreatic cancer patients.The patients of group A underwent PD combined with PV/SMV resection and reconstruction,and the patients of group B were only treated with PD surgery.The complication rate and overall survival time after PD was compared between the 21 patients of pancreatic cancer with PV/SMV invaded by tumor and the 62 patients of pancreatichead cancer without PV/SMV invaded by tumor.'Results The average overall survival time of 21 patients of pancreatic cancer with PV/SMV invaded by tumor (group A) was 19.2 months,specifically with 1-year survival rate of 57.1％ (12/21),2-year survival rate of 28.6％ (6/21),and 3-year survival rate of 14.3％ (3/21).Meanwhile,the average overall survival time of group B was 19.4 months,specifically with 1-year survival rate of 58.1％ (36/62),2-year survival rate of 30.6％ (19/62),and 3-year survival rate of 14.5％ (9/62).The results indicated that no differences for overall survival time of patients treated with PD including 1,2,3-year survival rate between two groups were found (P ＞ 0.05).Conclusions For pancreatic cancer accompanied by PV/SMV invasion without invasion of SMA,CA and HCA,PD combined with PV/SMV resection and reconstruction are safe and feasible surgical procedures.The surgical reconstruction method was determined according to the location and length of the invaded vessels,and also there were no significant differences on the complication rate and overall survival time after PD between the pancreatic cancer patients with invasion of PV/SMV and the pancreatic head cancer patients without invasion of PV/SMV.

A UPLC method has been developed for simultaneous determination of nine furanocoumarins of Angelica dahurics,and was used for quality evaluation of A. dahurica from different habitats. ACQUITY UPLC BEH C18 chromatographic column was employed,the separation was performed with the mobile phase consisting of acetonitrile and water,and the detection wavelength was set at254 nm. This method was used to simultaneously determine the content of xanthotoxol,oxypeucedaninhydrate,byak-angelicin,psoralen,xanthotoxin,bergapten,oxypeucedanin,imperatorin and isoimperatorin in A. dahurica from different habitats. Then,the further quality assessment of the drug was carried out by similarity evaluation,cluster analysis( CA),principal component analysis( PCA),and orthogonal partial least squares discriminant analysis( OPLS-DA). The content order of measured furanocoumarins from high to low was: oxypeucedanin>imperatorin>isoimperatorin>oxypeucedaninhydrate>bergapten>byak-angelicin>xanthotoxin>xanthotoxol>psoralen,with the mean content 2. 844,1. 277,0. 649 2,0. 216 2,0. 129 8,0. 062 68,0. 052 68,0. 019 30,0. 018 19 mg·g-1,respectively. There were difference between the batches of the drug,and the quality was influenced by smouldering sulphur based on the results of chemical pattern recognition and content determination. Finally,six active ingredients were recognized as the quality makers using OPLS-DA method. The validated UPLC fingerprint combined with chemical pattern recognition method can be used in the quality control and evaluation of A. dahurica.
Angelica ; chemistry ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; standards ; Ecosystem ; Furocoumarins ; analysis ; Quality Control

The aim of the present study was to investigate the role of ferroptosis in acute lung injury (ALI) mouse model induced by oleic acid (OA). ALI was induced in the mice via the lateral tail vein injection of pure OA. The histopathological score of lung, lung wet-dry weight ratio and the protein content of bronchoalveolar lavage fluid (BALF) were used as the evaluation indexes of ALI. Iron concentration, glutathione (GSH) and malondialdehyde (MDA) contents in the lung tissues were measured using corresponding assay kits. The ultrastructure of pulmonary cells was observed by transmission electron microscope (TEM), and the expression level of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA was detected by quantitative polymerase chain reaction (q-PCR). Protein expression levels of glutathione peroxidase 4 (GPX4), ferritin and transferrin receptor 1 (TfR1) in lung tissues were determined by Western blot. The results showed that histopathological scores of lung tissues, lung wet-dry weight ratio and protein in BALF in the OA group were higher than those of the control group. In the OA group, the mitochondria of pulmonary cells were shrunken, and the mitochondrial membrane was ruptured. The expression level of PTGS2 mRNA in the OA group was seven folds over that in the control group. Iron overload, GSH depletion and accumulation of MDA were observed in the OA group. Compared with the control group, the protein expression levels of GPX4 and ferritin in lung tissue were down-regulated in the OA group. These results suggest that ferroptosis plays a potential role in the pathogenesis of ALI in our mouse model, which may provide new insights for development of new drugs for ALI.
Acute Lung Injury ; chemically induced ; pathology ; Animals ; Apoptosis ; Bronchoalveolar Lavage Fluid ; chemistry ; Cyclooxygenase 2 ; metabolism ; Ferritins ; metabolism ; Glutathione ; analysis ; Glutathione Peroxidase ; metabolism ; Iron ; analysis ; Iron Overload ; physiopathology ; Lung ; cytology ; pathology ; Malondialdehyde ; analysis ; Mice ; Microscopy, Electron, Transmission ; Mitochondrial Membranes ; ultrastructure ; Oleic Acid

Objective:To observe effect of Zeqi Tang in intervening mice with orthotopic lung cancer model, in order to observe its anti-tumor mechanism. Method:An in situ mouse model of non-small cell lung cancer was established through intrapulmonary injection with 1×10⁵ LLC-luc cells. The model mice were intragastrically administered with Zeqi Tang(0.171 g·mL^-1) or normal saline for 35 days. Appearance (spirit, hair, appetite, sleep), survival period and Zeqi Tang anti-tumor effect were observed, weekly vital imaging was performed to detect the fluorescence signal in the lungs of mice. Flow cytometry was used to detect the NK cell content in the spleen of the model mice. CD107α was used to detect the degranulation of NK cells in the spleen of mice after administration of Zeqi Tang. Kromasil 100 5 C₁₈ column was used and eluted with acetonitrile-0.025%phosphoric acid in a gradient mode, with flow rate at 1.0 mL·min^-1, column temperature at 35℃ and detection wavelength of 265 nm, as to establish the fingerprint of Zeqi Tang. The fingerprints of 10 batches of samples was evaluated by using the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System Software (2012 Edition) recommended by the Chinese Pharmacopoeia Commission, in order to complete the quality control of Zeqi Tang. Result:Zeqi Tang could significantly inhibit the lung fluorescence signal of lung cancer in situ model mice and prolong the survival of mice(P<0.05, P<0.01). After the intervention with Zeqi Tang, the NK cells in the tumors increased significantly(P<0.01), and the degranulation of CD107α also increased significantly(P<0.01). Moreover, the HPLC-DAD fingerprint of Zeqi Tang showed a significant increase in the fingerprint similarity of 10 batches of lacquer soup aqueous extract. Moreover, the HPLC-DAD fingerprint of Zeqi Tang showed that the fingerprint similarity of 10 batches of lacquer soup aqueous extract was ≥ 0.9, indicating that small differences between the batches. Conclusion:Zeqi Tang may enhance the tumor growth and prolong the survival period of mice by up-regulating the number of NK cells in mice and enhancing their degranulation function. The evaluation of similarity of HPLC fingerprint of Zeqi Tang reflects the quality of lacquer soup to a certain extent, and can provide reference for further study.