Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

Objective:To discuss the promotive effect of Shengji Yuhong Ointment extract(SYOE)on skin wound healing of zebrafish,and to clarify its mechanism.Methods:A total of 320 wild-type AB strain zebrafish were used to establish a wound model by making an incision on the lateral abdomen.The zebrafish were randomly divided into control group,low dose of SYOE group(raised in water containing 0.625 mg·L-1 SYOE),high dose of SYOE group(raised in water containing 1.250 mg·L-1 SYOE),and allantoin group(raised in water containing 1.000 mng·L-1 allantoin),and there were 80 zebrafish in each group.The wound areas were recorded by photographs on days 7,14,and 21 after injury,and the wound healing rates were calculated.The skin tissue samples from the wound sites of the zebrafish in various groups were collected at different time points to prepare histological sections.HE staining was used to observe the widths of skin wound edges of the zebrafish on days 0,7,14,and 21 in various groups;Sirius red staining was used to detect the collagen levels in the wound tissues of the zebrafish on days 2,4,6,and 8 after injury in various groups;enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of type Ⅰ collagen(Col Ⅰ)and α-smooth muscle actin(α-SMA)in the wound tissues on day 4 after injury;real-time quantitative PCR(RT-qPCR)was used to analyze the mRNA expression levels of Col Ⅰ-encoding genes(col1a1a,col1a1b,and col1a2)and α-SMA as wall as key factors of the transforming growth factor β(TGF-β)/Smad signaling pathway(tgfb1a,smad2,and smad3a)in the wound tissues of the zebrafish in various groups on day 4 after injury.Results:The wound healing assessment results showed that compared with control group,the wound healing rates of the zebrafish in low dose of SYOE group,high dose of SYOE group,and allantoin group were significantly increased on days 7,14,and 21 after injury(P＜0.05 or P＜0.01);the wound healing rate in high dose of SYOE group achieved 84％on day 21.The HE staining results showed that compared with control group,the widths of skin wound edges of the zebrafish in low dose of SYOE group,high dose of SYOE group,and allantoin group were significantly decreased on days 14 and 21 after injury(P＜0.05 or P＜0.01).The Sirius red staining results showed that compared with control group,the collagen levels in the skin wound tissue of the zebrafish in low dose of SYOE group,high dose of SYOE group,and allantoin group were significantly increased on days 6 and 8 after injury(P＜0.01).The ELISA results showed that on day 4 after injury,compared with control group,the levels of Col Ⅰ and α-SMA in the skin wound tissue of the zebrafish in low dose of SYOE group,high dose of SYOE group,and allantoin group were significantly increased(P＜0.05 or P＜0.01).The RT-qPCR results showed that on day 4 after injury,compared with control group,the expression levels of col1a1b,col1a2,α-SMA,tgfb1a,and smad2 mRNA in the skin wound tissue of the zebrafish in low dose of SYOE group were significantly increased(P＜0.05 or P＜0.01),while the expression levels of col1a1a,col1a1b,col1a2,α-SMA,tgfb1a,smad2,and smad3a mRNA in the skin wound tissue of the zebrafish in high dose of SYOE group and allantoin group were significantly increased(P＜0.01).Conclusion:SYOE can increase the collagen deposition in skin wound of zebrafish,promote wound healing,and upregulate the expression of genes related to the TGF-β/Smad signaling pathway.

Objective:To investigate the effect of Chinese Herbal Anti-Alopecia and Hair Growth Solution(CHAaHGS)on the hair growth through in vitro experiments on the human dermal papilla cells(HDPCs),in vivo experiments in the C57BL/6 mice,and human efficacy tests,and to clarify its potential mechanism.Methods:The HDPCs were divided into control group,CHAaHGS group,and minoxidil group.MTT method was used to detect the proliferation activities of HDPCs in various groups;enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of vascular endothelial growth factor(VEGF),hepatocyte growth factor(HGF),insulin-like growth factor-1(IGF-1),and transforming growth factor β1(TGF-β1)in the supernatant of HDPCs in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of VEGF,HGF,IGF-1,TGF-β1,and alkaline phosphatase(ALP)mRNA in the HDPCs in various groups;Western blotting method was used to detect the expression levels of β-catenin,dishevelled segment polarity protein 1(DVL1),glycogen synthase kinase 3β(GSK-3β),phosphorylated GSK-3β(p-GSK-3β),and wingless-type MMTV integration site family member 3a(Wnt3a)proteins in the HDPCs in various groups.A total of 18 mice were randomly divided into control group,CHAaHGS group,and minoxidil group,with 6 mice in each group.The mouse hair loss model was established using hair removal cream,and corresponding drug treatments were administered immediately after hair removal.The lengths and weights of newly grown hair on day 21 of the mice in various groups were detected;HE staining was used to observe the morphology of hair follicles in the dorsal depilated skin areas of the mice in various groups on day 7;ELISA method was used to detect the levels of VEGF,HGF,IGF-1,and TGF-β1 in the skin tissue of dorsal depilated areas of the mice in various groups.Sixty subjects were randomly divided into control group and CHAaHGS group,with 30 subjects in each group.The numbers of hair loss and hair densities of the subjects in various groups were detected at weeks 0,4,8,and 12.Results:The MTT assay results showed that compared with control group,the proliferation activity of the cells in 50 mg·L-1CHAaHGS group was significantly increased(P＜0.01).The ELISA assay results showed that compared with control group,the levels of VEGF,HGF,and IGF-1 in the cell supernatant of HDPCs in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the TGF-β1 level was significantly decreased(P＜0.01).The RT-qPCR results showed that compared with control group,the expression levels of VEGF,HGF,IGF-1,and ALP mRNA in the cells in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the TGF-β1 mRNA expression level was significantly decreased(P＜0.01).The Western blotting results showed that compared with control group,the expression levels of β-catenin,DVL1,p-GSK-3βand Wnt3a proteins in the cells in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the GSK-3β protein expression level was significantly decreased(P＜0.05).In animal experiments,on day 21,compared with control group,the length of newly grown hair of the mice in CHAaHGS group was significantly increased(P＜0.05),and the hair weight was significantly increased(P＜0.01).On day 7,the HE staining results showed that compared with control group,the hair follicle spacing of the mice in CHAaHGS group was significantly decreased(P＜0.05),and the number of hair follicles was significantly increased(P＜0.01);the ELISA assay results showed that compared with control group,the levels of VEGF,HGF,and IGF-1 in skin tissue of dorsal depilated area of the mice in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the TGF-β1 level was significantly decreased(P＜0.05).In human efficacy test,compared with control group,the number of hair loss of the subjects in CHAaHGS group was significantly decreased at week 12(P＜0.01),and the local hair density was increased(P＜0.05).Conclusion:CHAaHGS promotes hair growth,and the mechanism may be related to its ability to increase the proliferation activity of HDPCs,induce the secretion of VEGF,HGF,and IGF-1,and activate the Wnt/β-catenin signaling pathway.

Gelsemium elegans (G. elegans) is an extremely poisonous plant that is widely distributed in southern China and southeastern Asia. G. elegans poisoning events occur frequently in southern China, and are therefore an urgent public health problem requiring multidisciplinary action. However, the toxic components and toxicological mechanisms remain unclear. Here, we describe a systematic investigation on the toxic components of G. elegans, resulting in the isolation and identification of 120 alkaloids. Based on acute toxicity screening, the structure-toxicity relationship of Gelsemium alkaloids was proposed for the first time. Moreover, gelsedine- and humantenine-type alkaloids were detected in the clinical blood sample, and were confirmed to be causative in the poisoning. The most toxic compound, gelsenicine (1), had selective inhibitory effects toward ventral respiratory group (VRG) neurons in the medulla, which is the main brain region controlling respiration in the central nervous system. Gelsenicine (1) strongly inhibited the firing of action potentials in VRG neurons through its ability to stimulate GABA_A receptors, the main receptors involved in inhibitory neurotransmission. Application of GABA_A receptor antagonists successively reversed action potential firing in gelsenicine (1)-treated VRG neurons. Importantly, the GABA_A receptor antagonists securinine and flumazenil significantly increased the survival of poisoned animals. Our findings provide insight into the components and mechanisms of G. elegans toxicity, and should assist the development of effective emergency treatments for G. elegans poisoning.

Objective: To analyze the association and dose response relationship between physical activity and inflammatory markers in college students, so as to provide a reference for promoting cardiometabolic health in college students. Methods: A cluster random sampling method was used to select 747 college students from two universities in Hefei, Anhui Province and Shangrao, Jiangxi Province from April to May 2019. Physical activity was assessed by using the International Physical Activity Questionnaire-Short Form (IPAQ-SF), and peripheral blood was collected to detect plasma inflammatory factor levels [including hypersensitive C reactive protein (hsCRP), interleukin-10 (IL-10), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)]. The differences between the groups were compared by using the χ 2 test and the Kruskal-Wallis rank sum test, and the association between physical activity and inflammatory markers was analyzed by using the Generalized Linear Model. The dose response relationship between physical activity and inflammatory markers was analyzed using the Restricted Cubic Spline Model. Results: The proportions of low physical activity, moderate physical activity, and high physical activity groups of college students were 15.9%, 53.7% and 30.4%, respectively. The levels of hsCRP, IL-10, IL-1β, IL-6 and TNF-α in the high physical activity group were 0.38(0.21, 1.10)mg/L, 70.74(47.90, 116.43)pg/mL, 1.75(1.21, 2.64)pg/mL, 4.33(2.93, 6.82) pg/mL , 5.27(3.89, 7.30)pg/mL,the levels in the low physical activity group were 0.80(0.31, 1.30)mg/L, 73.88 (47.90, 124.24)pg/mL, 1.88(1.42, 2.81) pg/mL, 4.82 (3.64, 6.67) pg/mL, 5.63 (4.34, 7.62)pg/mL, the levels in the moderate physical activity group were 0.63(0.25, 1.30)mg/L, 89.78(58.21, 127.65)pg/mL, 2.21(1.59, 3.27)pg/mL, 5.15( 3.72 , 7.72)pg/mL, 5.87( 4.63 , 8.00)g/mL, and the differences were statistically significant ( H=10.66, 11.38, 27.79, 14.13, 9.44, P <0.05). After adjusting for variables such as gender, body mass index, smoking, alcohol consumption and health status, the results of Generalized Linear Model showed that compared with the high physical activity group, the low physical activity group ( OR=2.20, 95%CI = 1.46- 3.31) and the moderate physical activity group ( OR=1.65, 95%CI =1.22-2.25) were more likely to have high levels of hsCRP, and the moderate physical activity group was more likely to have high levels of IL-1β ( OR=1.85, 95%CI =1.36-2.51), IL-6 ( OR=1.44, 95%CI =1.06-1.96), and TNF-α ( OR=1.43, 95%CI =1.05-1.94) ( P <0.05). The Restricted Cubic Spline Model showed that there was no linear dose response relationship between the time of moderate to vigorous physical activity weekly and IL-10, IL-6, II-1β, and TNF-α ( P <0.05). Conclusion There is an association between physical activity and inflammation in college students, and moderate to high intensity per week could reduce inflammation levels to promote cardiometabolic health in college students.

Objective To understand the economic losses due to healthcare-associated infection(HAI)in patients after Da Vinci robotic thoracic surgery,and provide basis for preventing and controlling HAI after robotic surgery.Methods Patients who underwent Da Vinci robotic surgery from April 2019 to April 2023 were retrospective stu-died.Patients were divided into HAI group and non-HAI group based on the occurrence of postoperative infection.Through 1∶1 propensity score matching(PSM),31 cases were included in each group,economic losses of two groups of patients were compared.Results A total of 921 patients who underwent Da Vinci robotic thoracic surgery were included in the study,51 cases with HAI(HAI group)and 870 without HAI(non-HAI group).After 1∶1 PSM,31 cases were included in each group.Four covariates were compared between two groups of patients before PSM,namely gender,age,comorbidities,and the American Society of Anesthesiologists(ASA)grading,all with statistically significant differences(all P＜0.05).After PSM,distribution of the above covariates reached equilib-rium between the two groups(both P＞0.05).The median total expense for HAI group before PSM during hospi-talization was 88 711.72 Yuan,while 78 509.46 Yuan for the non-HAI group.The direct economic losses caused by HAI after Da Vinci robot surgery was 10 202.26 Yuan,mainly increased by expense of medicine,nursing,laborato-ry diagnosis,etc.Difference in western medicine expense was the highest(8 839.12 Yuan),out of which expense of antimicrobial agents accounted for the highest proportion(73.55％).Difference in daily hospitalization expense between HAI-group and non-HAI group was 502.38 Yuan.Length of hospital stay of patients in HAI group and non-HAI group were(21.59±10.62)and(13.92±9.21)days,respectively,with statistical differences(all P＜0.05).Conclusion The occurrence of HAI in patients undergoing Da Vinci robotic thoracic surgery leads to direct economic losses,with obvious increases in expenses of nursing,laboratory diagnosis,western medicine(mainly an-timicrobial agents).Length of hospital stay of patients also prolongs.

Background and Aims:Abdominal aortic aneurysm(AAA)is a common arterial dilation disease in vascular surgery,with aneurysm rupture being its most serious complication,often leading to fatal hemorrhage and posing a severe threat to patients'lives.Endovascular aneurysm repair(EVAR),due to its minimally invasive nature,safety,and rapid recovery,has become the preferred treatment for AAA.However,endoleak,a complication unique to EVAR,remains a major clinical challenge.Persistent endoleak can lead to sustained high pressure within the aneurysm sac,increasing the risk of continued expansion and rupture.It is one of the main causes of the high reintervention rate following EVAR.In particular,the treatment strategy for type Ⅱ endoleaks remains controversial.This study was conducted to evaluate the clinical value of selective sac embolization via the iliac approach combined with standard EVAR in managing intraoperative immediate endoleaks.Methods:The clinical data of AAA patients with a risk of endoleak who underwent standard EVAR at the First Hospital of China Medical University between March 2023 and September 2024 were retrospectively collected.Patients were divided into an intervention group(n=42)and a non-intervention group(n=32)based on whether selective sac embolization via the iliac approach was performed during operation.General clinical data,preoperative anatomical characteristics of the AAA,surgical details,and postoperative follow-up results were compared between the two groups.Results:There were no statistically significant differences between the two groups in terms of age,sex,anatomical features,rupture rate,or off-label use(all P>0.05).The technical success rate during surgery was 100%in both groups.One patient in the intervention group experienced transient sigmoid colon ischemia after operation,which resolved with conservative treatment.The mean follow-up period was(6.49±4.68)months.The proportions of aneurysm sac shrinkage,stability,and enlargement in the intervention group were 40.5%,57.1%,and 2.4%,respectively,compared to 59.4%,40.6%,and 0.0%in the non-intervention group,with no statistically significant differences(all P>0.05).The incidence of endoleak during follow-up was also comparable between the two groups(P>0.05).Conclusion:For intraoperative endoleaks during standard EVAR,selective sac embolization via the iliac approach is a technically simple and safe method that provides short-term outcomes comparable to those in patients without intraoperative endoleaks.Its long-term efficacy warrants further investigation through extended follow-up.

Porcine reproductive and respiratory syndrome virus(PRRSV)mainly causes sow abor-tion,stillbirth,mummified fetus and respiratory symptoms in piglets.Since first reported in China in 1996,the virus complexity has increased significantly in more than 20 years of genetic evolution,bringing huge economic losses to the pig industry.In recent years,with the emergence of various PRRSV recombinant virus strains,preventing and controlling this epidemic became increasingly difficult.The purpose of this article is to comprehensively review the genome structure and func-tion of PRRSV,RNA virus recombination mechanism,main types of recombination,and the epi-demic status and recombination for the dominant epidemic PRRSV strains,in order to provide clues for in-depth research on gene recombination of PRRSV,thus providing the theoretical sup-port for formulating scientific prevention and control strategies.

OBJECTIVE To observe the isolation rates and drug resistance rates of Acinetobacter baumannii strains isolated from intensive care unit(ICU)patients in 8 consecutive years so as to provide bases for reasonable clinical application of antibiotics and control of infections.METHODS The isolation rates and specimens from which the A.baumannii and carbapenem-resistant A.baumannii(CRAB)strains were isolated from ICU patients of the First People's Hospital of Changzhou between 2017 and 2024 were retrospectively analyzed.The trends of the drug resistance rates were observed.RESULTS Totally 2078(18.03％)strains of A.baumannii were isolated from the ICU patients from 2017 to 2024,and there was no significant difference in the changing trend among the years(x2=-1.573,P=0.116).Among the A.baumannii strains that were isolated from 2017 to 2024,58.08％were isolated from sputum,and 24.25％from lavage fluid specimens;the percentage of sputum specimens showed a downward trend in the 8 years(x2=-8.257,P＜0.001),while the percentage of lavage fluid speci-mens showed an upward trend(x2=12.964,P＜0.001).The isolation rate of the CRAB strains was 91.48％in 2017,92.61％in 2018,92.56％in 2019,82.53％in 2020,52.44％in 2021,showing a down-ward trend,and it began to rise in 2022-2024,there was significant difference(x2=-2.277,P=0.012).The isolation rates of the CRAB strains from both sputum and lavage fluid specimens showed downward trends and then upward trends(all P＜0.05).The drug resistance rates of the A.baumannii strains to piperacillin and minocycline showed slow upward trends,while the drug resistance rates to gentamicin and tigecycline showed downward trends,and there were significant differences(P＜0.05).The drug resistance rates of the A.bau-mannii strains to imipenem and meropenem remained more than 90％.CONCLUSIONS Acinetobacter spp is the major pathogen causing the hospital-acquired infection.The isolation rate of CRAB strains shows a downward trend then a upward trend in recent two years.It is necessary for the hospital to standardize the submission of spu-tum specimens and increase the aseptic submission.The A.baumannii strains show high drug resistance rates to the commonly used antibiotics.Polymyxin B,tigecycline and minocycline are the major antibiotics for treatment of CRAB infection.

Background and Aims:Abdominal aortic aneurysm(AAA)is a common arterial dilation disease in vascular surgery,with aneurysm rupture being its most serious complication,often leading to fatal hemorrhage and posing a severe threat to patients'lives.Endovascular aneurysm repair(EVAR),due to its minimally invasive nature,safety,and rapid recovery,has become the preferred treatment for AAA.However,endoleak,a complication unique to EVAR,remains a major clinical challenge.Persistent endoleak can lead to sustained high pressure within the aneurysm sac,increasing the risk of continued expansion and rupture.It is one of the main causes of the high reintervention rate following EVAR.In particular,the treatment strategy for type Ⅱ endoleaks remains controversial.This study was conducted to evaluate the clinical value of selective sac embolization via the iliac approach combined with standard EVAR in managing intraoperative immediate endoleaks.Methods:The clinical data of AAA patients with a risk of endoleak who underwent standard EVAR at the First Hospital of China Medical University between March 2023 and September 2024 were retrospectively collected.Patients were divided into an intervention group(n=42)and a non-intervention group(n=32)based on whether selective sac embolization via the iliac approach was performed during operation.General clinical data,preoperative anatomical characteristics of the AAA,surgical details,and postoperative follow-up results were compared between the two groups.Results:There were no statistically significant differences between the two groups in terms of age,sex,anatomical features,rupture rate,or off-label use(all P>0.05).The technical success rate during surgery was 100%in both groups.One patient in the intervention group experienced transient sigmoid colon ischemia after operation,which resolved with conservative treatment.The mean follow-up period was(6.49±4.68)months.The proportions of aneurysm sac shrinkage,stability,and enlargement in the intervention group were 40.5%,57.1%,and 2.4%,respectively,compared to 59.4%,40.6%,and 0.0%in the non-intervention group,with no statistically significant differences(all P>0.05).The incidence of endoleak during follow-up was also comparable between the two groups(P>0.05).Conclusion:For intraoperative endoleaks during standard EVAR,selective sac embolization via the iliac approach is a technically simple and safe method that provides short-term outcomes comparable to those in patients without intraoperative endoleaks.Its long-term efficacy warrants further investigation through extended follow-up.