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 To establish the fingerprint of Pinghuo tea standard decoction and a method for determination of multi-component to clarify the transfer relationship of quantities and quality from pieces and standard decoction. METHODS Fifteen batches of Pinghuo tea standard decoction were prepared and the extract rate was determined； the fingerprint of the preparation was established by using high-performance liquid chromatography（HPLC）； the similarity evaluation and the determination of common peaks were performed， and chemometric analysis was performed； the same method was used to determine the content of indicator components and the transfer rate was calculated. The chromatographic column was Venusil C18 column with mobile phase consisted of acetonitrile-0.1% phosphoric acid solution （gradient elution）； the column temperature was 30 ℃， and the detection wavelengths were 238 nm （0-37 min， 85-102 min） and 330 nm （37-85 min） at a flow rate of 1.0 mL/min with an injection volume of 10 μL. RESULTS The similarity of HPLC fingerprints for 15 batches of Pinghuo tea standard decoction was not lower than 0.968. A total of 24 common peaks were calibrated and 9 peaks were recognized， which were as follows neochlorogenic acid （peak 3）， chlorogenic acid （peak 6）， geniposide （peak 9）， glycyrrhizin （peak 10）， galuteolin （peak 11）， isochlorogenic acid A （peak 14）， luteolin （peak 21）， kaempferol （peak 23） and glycyrrhizic acid （peak 24）. Cluster analysis， principal component analysis and orthogonal partial least squares discriminant analysis showed consistent results， all of which could classify the 15 batches of samples into three categories. The linear range of indicator components in 15 batches of Pinghuo tea standard decoction， such as geniposide， luteolin， isochlorogenic acid A， glycyrrhizin， and glycyrrhizic acid， were 0.020 580-0.411 600， 0.001 617-0.080 850， 0.006 076-0.607 600， 0.005 125-0.071 740， and 0.017 288-0.432 200 mg/mL， respectively； RSDs of precision， repeatability， stability and recovery rate tests were all not higher than 4% （n＝6）. The mass fractions ranged 3.227 9-10.002 2， 0.297 4-0.554 6， 3.350 1-6.159 6， 0.720 6-1.073 3， 2.003 1-3.030 1 mg/g； transfer rates from the pieces and standard decoction were 19.762 8%-35.840 5%， 12.123 3%-21.254 0%， 46.097 2%-82.869 4%， 58.708 8%-91.629 6%， 39.114 3%-63.710 6%. The transfer rates of the extract from 15 batches of Pinghuo tea standard decoction ranged from 61.15%-84.68%. CONCLUSIONS Established HPLC fingerprint and content determination methods in this study are simple and accurate， which can provide reference for the quantitative value transfer study， quality control， clinical application and the development of subsequent formulations of Pinghuo tea standard decoction.

Objective To describe and analyze the epidemiological characteristics of scrub typhus in Huai'an, Jiangsu Province from 2006 to 2024 and explore the long-term incidence trend and distribution of high-risk areas, and to formulate targeted prevention and control strategies. Methods The scrub typhus case report data of Huai'an from 2006 to 2024 in the Chinese Disease Prevention and Control Information System were extracted for descriptive analysis. Results A total of 898 cases of scrub typhus were reported in Huai'an, with an average annual incidence rate of 0.96 per 100 000 from 2006 to 2024. There was a turning point in the incidence trend of scrub typhus in 2011. From 2006 to 2011, the annual percentage change (APC) was 47.09% (95% CI: 7.53 - 859.39), and the upward trend was statistically significant (P < 0.05). From 2012 to 2024, the APC was -2.12% (95% CI: -29.09 - 3.75), and the downward trend was not statistically significant. October and November were the high-incidence months, and the total concentration from 2006 to 2024 was 0.93, indicating that scrub typhus had strict seasonality. The circular distribution method estimated that the peak period of the epidemic was from October 11th to November 25th, and the peak day of incidence was November 3rd. Jinhu County was a high-incidence area. The ratio of male to female cases was 1.03. The age group with the highest reported incidence was 40 to < 80 years old. The occupation with the highest proportion was farmers, accounting for 78.03%. Conclusion From 2006 to 2024, scrub typhus in Huai'an shows a peak every 3 - 4 years. Middle-aged and elderly farmers are the key population at risk, and Jinhu County is a key area. In the future, targeted health education should be carried out to effectively control the prevalence of scrub typhus.

Diabetic macular edema(DME)is a complication of diabetic retinopathy(DR), and is also the main cause of vision loss and blindness in DR patients. Optical coherence tomography(OCT)and optical coherence tomography angiography(OCTA)serve as the principal methods for the non-invasive assessment of microstructural and microvascular pathological changes in the retina. They are widely-used methods for detecting and evaluating DME. As OCT and OCTA technologies advance, various parameters have assumed the role of biomarkers, such as central subfield thickness(CST), cube average thickness(CAT), cube volume(CV), disorganization of retinal inner layers(DRIL), hyperreflective foci(HRF)and subfoveal neuroretinal detachment(SND). OCT and OCTA are widely used in clinical practice. OCT can visually show the layer changes and subtle structures of the retina and choroid in the macular area, while OCTA is more often used to detect microvascular changes. In this article, the role of OCT and OCTA-related biomarkers in prognosis and monitoring in DME is described, while the biomarkers visible in the test results can provide new ideas for monitoring and treatment strategies in DME, and provide new insights into the pathogenesis of DR and DME.

ObjectiveBased on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway， this paper explores the effect of Sinisan （SNS） on liver oxidative stress injury in cholestatic hepatitis rats and its mechanism. MethodThirty 6-week-old male SD rats were randomly divided into a control group， model group， low and high dose groups of SNS （2.5 and 5 g·kg^-1） and ursodeoxycholic acid group （UDCA， 63 mg·kg^-1）， with six rats in each group. Rats were administrated for seven consecutive days. On the 5th day， the control group was given olive oil of 10 mL·kg^-1， and the other groups were given alpha-naphthalene isothiocyanate （ANIT） of 80 mg·kg^-1. The serum biochemical indicator levels of cholestasis and the content of antioxidant factors in rat liver were detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in liver tissue. The relative mRNA and protein expressions of Nrf2， HO-1， and quinone oxidoreductase 1 （NQO1） in liver tissue were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the control group， the model group showed a significant increase in the serum biochemical indicator levels of cholestasis and the content of antioxidant factors in liver tissue （P<0.01）. There were obvious pathological changes in the model group such as the disordered arrangement of hepatocytes， obvious congestion and necrosis in the portal area， infiltration of inflammatory cells， and destruction of the interlobular bile duct. The relative mRNA and protein expressions of Nrf2， HO-1， and NQO1 in liver tissue were significantly down-regulated in the model group （P<0.05， P<0.01）. Compared with the model group， the groups of SNS showed a significant decrease in the serum biochemical indicator levels of cholestasis and the content of antioxidant factors in liver tissue （P<0.01）， and the pathological liver injury was obviously improved. The necrotic area was reduced， and the infiltration of inflammatory cells was decreased. In addition， there was a small amount of extravasated blood in the interlobular vein. The relative mRNA and protein expressions of Nrf2， HO-1， and NQO1 in liver tissue were significantly up-regulated （P<0.05， P<0.01）. ConclusionSNS can significantly improve liver injury in cholestatic hepatitis rats， and its mechanism may be related to the inhibition of oxidative stress response mediated by the Nrf2/HO-1 signaling pathway.

Objective:To discuss the regulatory effect of berberine(BBR)on fatty acids in the human glioma T98G cells and its effect on the cell proliferation,migration,and invasion,and to clarify its potential mechanism.Methods:The T98G cells at logarithmic growth phase were divided into control group and different concentrations(25,50,and 100 mg·L-1)of BBR groups.Cell wound healing assay was used to detect the migration rates of the cells in various groups;Transwell chamber assay was used to detect the invasion rates of the cells in various groups.The T98G cells at logarithmic growth phase were divided into control group and 100 mg·L-1 BBR group,and Mass spectrometry was used to detect the fatty acid contents in the cells in two groups.The T98G cells at logarithmic growth phase were divided into control group and different concentrations(50,100,and 150 mg·L-1)of BBR groups;Western blotting method was used to detect the expression levels of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(AKT),phosphorylated AKT(p-AKT),sterol regulatory element-binding protein 1(SREBP-1),and fatty acid synthase(FASN)in the cells in various groups.The expression of FASN was suppressed by gene silencing technology,and the T98G cells at logarithmic growth phase were divided into control group,shFASN1 group,and shFASN2 group.Western blotting method was used to detect the expression levels of FASN protein in the cells in various groups;clone formation assay was used to detect the clone formation of the cells in various groups;cell wound healing assay was used to detect the migration rates of the cells in various groups.Results:Compared with control group,the migration rates and invasion rates of the cells in different concentrations of BBR groups were decreased in a concentration-dependent manner(P<0.01),and the fatty acid content in the cells in 100 mg·L-1 BBR group was significantly decreased(P<0.01).Compared with control group,the expression levels of p-PI3K,p-AKT,SREBP-1,and FASN proteins in the cells in 150 mg·L-1 BBR group were significantly decreased(P<0.05 or P<0.01),and the expression level of SREBP-1 protein in the cells in 100 and 150 mg·L-1 BBR groups were significantly decreased(P<0.01).After suppression of FASN expression,compared with control group,the expression levels of FASN protein in the cells in shFASN1 and shFASN2 groups were significantly decreased(P<0.01),and the expression level of FASN protein in the cells in shFASN2 group was lower than that in shFASN1 group(P<0.05);compared with control group,the numbers of clone formation and migration rates of the cells in shFASN1 and shFASN2 groups were significantly decreased(P<0.01),and the migration rate of the cells in shFASN2 group was significantly lower than that in shFASN1 group(P<0.05).Conclusion:BBR interferes with fatty acid synthesis in the glioma T98G cells by reducing the expression of the PI3K/AKT/SREBP-1/FASN pathway related proteins,and decrease their migration and invasion capabilities.

BACKGROUND:As a unique structure of the cervical spine,the occurrence,development and progression of the uncovertebral joint directly affect the stability and range of motion of the cervical spine,and are also closely related to the pathogenesis of cervical spondylosis.A thorough understanding of the developmental characteristics of the uncovertebral joint is of great significance for the pathogenesis,diagnosis,and treatment of cervical spondylosis. OBJECTIVE:By using imaging and three-dimensional reconstruction technology to measure and observe the cervical uncinate process-related angle in a large sample of different age groups,the aim is to reveal the characteristics of its changes with age and vertebral growth,as well as its relationship with cervical spine stability. METHODS:Using a retrospective research design,we collected 1 447 cases of raw CT imaging data that meet the study requirements for complete cervical spine segments.The raw data were imported into Mimics 21.0 software in DICOM format for post-processing and measurement of angle of uncinate process and sagittal angle of uncinate process.The data were grouped based on gender,age,and side. RESULTS AND CONCLUSION:(1)With the increase of vertebral sequence,the angle of uncinate process increased in a V-shaped shape,and the lowest peak was at C5.The overall population showed a sharp peak with the increase of age,and the peak value mostly occurred in the age range of 30-39 years.(2)The sagittal angle of the uncinate process increased like a fishhook with the increase of the vertebral sequence,and the overall angle of the uncinate process increased with age,and the peak value mostly occurred in the age range of 20-29 years.The uncinate process angle and sagittal angle showed only partial significant differences between sides and genders(P<0.05).(3)It is concluded that the angle of the uncinate process increased with the increase of vertebral sequence in a V-shaped manner.The sagittal angle of the uncinate process increases like a fish hook with increasing vertebral order,while the two angles generally peak with increasing age.The angle of the uncinate process is about 131°,which may be closely related to the stability of the cervical spine,while the sagittal angle of the uncinate process is about 14°,and its function may play a certain role in limiting the excessive rotation of the cervical spine.

ObjectiveTaking Achyranthis Bidentatae Radix（ABR） from different origins as samples， to quantitatively analyze the chemical composition and chromaticity of ABR with different processing degrees， and clarify the correlation and change law between color and composition in the processing process of ABR， so as to provide reference for the quality evaluation of processed products of ABR. MethodThe colorimeter is used to measure the chromaticity values of three kinds of processing degrees of ABR in different origins to show the color value change trend during the processing process， and the color parameters of wine-processed and salt-processed products of ABR with different processing degrees were analyzed by principal component analysis（PCA）， orthogonal partial least squares-discriminant analysis（OPLS-DA） and other analysis methods. The contents of eight representative components of ABR were measured by high performance liquid chromatography（HPLC）， the correlation between chromaticity and each representative component was analyzed by Pearson correlation analysis， and the applicability of the selected eight representative components was further verified by Fisher linear discriminant analysis， and the wine-processed and salt-processed products of ABR with different processing degrees were grouped according to the degree of processing， and 48 samples of wine-processed and salt-processed products with different processing degrees were used as training samples. Taking the contents of 5-hydroxymethylfurfural， polypodine B， β-ecdysterone， 25R-inokosterone， 25S-inokosterone， ginsenoside Ro， chikusetsusaponin Ⅳa and polysaccharides as variables， the discriminant function was established respectively， and 12 samples of wine-processed and salt-processed products of ABR with different processing degrees were back-tested to verify the discriminant function and test the reliability of the function. ResultPCA and OPLS-DA results showed that ABR samples with different processing degrees were classified into clusters， and the results could significantly distinguish different processed products. During the process of wine and salt processing， the contents of 5-hydroxymethylfurfural， ginsenoside Ro_， and chikusetsusaponin Ⅳa gradually increased with the deepening of the processing degree， while the contents of polypodine B， β-ecdysterone， 25R-inokosterone， 25S-inokosterone and polysaccharides showed a gradual decreasing trend， indicating these 8 components increased and decreased to different degrees in the process of wine and salt processing. The results of Pearson correlation analysis showed that the 5-hydroxymethylfurfural content of the samples with different processing degrees of wine-processed and salt-processed products were negatively correlated with the brightness value（L^*） and the total color difference value（E^*ab）（P<0.01）， and positively correlated with the red-green value（a^*） and the yellow-blue value（b^*）（P<0.01）， and that the content of polypodine B and polysaccharides were positively correlated with L^* and E^*ab（P<0.01）. The discriminant functions of wine-processed and salt-processed products of ABR were established by Fisher linear discriminant analysis， and their accuracy rates in the training samples were 93.75% and 95.83%， respectively. Twelve test samples of wine-processed and salt-processed products with different processing degree were back substitution， and the correct rate was 100%. ConclusionThe trend of composition and color changes of ABR with different processing degrees in different production areas is relatively consistent， and the color value can better distinguish ABR with different processing degrees， and the color of ABR is related to some representative components in the processing process， indicating that the color can provide reference for the identification of the processing degree of ABR and the prediction of component content.

Tracheostomy is a very common airway procedure in the treatment of critically ill neurological patients. At present, the traditional tracheal cannula fixation belt is easy to be contaminated, difficult to disinfect, and needs to be replaced regularly. It is prone to infection, skin injury, unplanned extubation and other adverse events, which cannot meet the clinical treatment effect and patient safety management. In order to overcome the above problems, the medical staff of the neurology intensive care unit of Henan Provincial People's Hospital designed a new type of tracheal cannula fixation belt to increase patient comfort and reduce complications, and obtained a National Utility Model Patent of China (ZL 2022 2 0855188.8). The main structure of the device includes a following shaped bending plate, a fastening belt, a locking pin, and a distance adjustment hole. The left and right sides of the shaped bending plate are equipped with fastening belts with breathable and anti-wear pads. The inner side of the left fastening belt is equipped with two sets of locking pins, and the outer surface of the right fastening belt and breathable and anti-wear pad is equipped with multiple sets of distance adjustment holes. Additionally, the back of the shaped bending plate is equipped with breathable buffer pads. The fastening belt can drive the following bending plate to stick tightly to the patient's neck. The operator installs the locking pin card into the distance adjustment hole according to the "one back" principle, and the fastening belts on both sides fix the device with the cooperation of the locking pin, greatly reducing the probability of excessive displacement of the tracheal tube during use, effectively improving the fixation effect of the device, strengthening the adaptability of the device to different personnel, and thus enhancing the practicality of the device. The new type of tracheal cannula fixation band is convenient, safe and efficient, which can increase patient comfort, reduce complications. It has certain clinical value and is suitable for clinical promotion.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).