Cholangiocarcinoma (CCA) is a malignant tumor originating from cholangiocytes. However, it remains unclear about the pathogenesis of this carcinoma, which may be related to multiple factors. Currently, CCA is mainly treated by surgery, chemotherapy, and radiotherapy. Among them, surgery is the only potentially curative option for CCA. Nevertheless, the high malignancy and asymptomatic nature of CCA may lead to poor treatment outcomes. It has been demonstrated that Chinese medicine (CM) plays a significant role in various antitumor applications. Meanwhile, CM exhibits fewer side effects and high availability. Moreover, the in vitro application of CM monomers has been explored in many domestic and foreign studies. This article mainly reviews the signaling pathways and molecular mechanisms of CM monomers in the treatment of CCA in recent years. These findings are expected to provide new insights into the treatment of CCA.
Cholangiocarcinoma/drug therapy* ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Bile Duct Neoplasms/drug therapy* ; Medicine, Chinese Traditional ; Animals ; Signal Transduction/drug effects*

Objective To investigate the values of serum procalcitonin (PCT), anti-thrombin Ⅲ (AT-Ⅲ), D-dimer (D-D), fibrinogen (FIB), thrombin time (TT), activated partial thromboplastin time (APTT), and prothrombin time (PT) in the early diagnosis of pediatric sepsis. Methods A total of 82 children with sepsis in the Pediatric Intensive Care Unit (PICU) of General Hospital of Hunan University of Medicine from June 2020 to June 2023 were selected as sepsis group. Meanwhile, 90 children with respiratory tract infections in the general ward were included in general infection group, and 100 healthy children in the Department of Pediatric Health were selected as control group. The levels of serum PCT, AT-Ⅲ, D-D, FIB, TT, APTT and PT were compared among the three groups. Results Compared with the general infection group and the control group, the sepsis group had significantly higher serum PCT and D-D levels, prolonged TT, APTT and PT in the four-items of coagulation test, and reduced AT-Ⅲ and FIB levels (P < 0.05). The areas under the curve (AUCs) for the diagnosis of pediatric sepsis by serum PCT, AT-Ⅲ, D-D, PT, APTT, TT and FIB levels were 0.949, 0.174, 0.911, 0.869, 0.855, 0.834 and 0.242 respectively; among these indexes, serum PCT showed the highest diagnostic value, with the maximum Youden index at a cut-off value of 0.62 μg/L, and the diagnostic sensitivity and specificity were 86.6% and 79.0% respectively. The AUC for the combined diagnosis of pediatric sepsis by the seven indicators was 0.966. Conclusion The detection of serum PCT, AT-Ⅲ, D-D and four items of coagulation test is of great value in the early diagnosis and differential diagnosis of pediatric sepsis.

Objective To understand the prevalence characteristics of influenza and changes of influenza virus strains,and provide reference for the prevention and control of influenza in the province.Methods Surveillance da-ta about influenza in Hunan Province from 2014 to 2023 were exported from China Influenza Surveillance Informa-tion System.Differences in the percentage of influenza-like illness(ILI)cases(percentage of influenza-like cases[ILI％]in outpatient and emergency department visits)among different years and different populations,as well as the positive rate of influenza virus in ILI specimens were compared.Results From 2014 to 2023,over 2.65 million cases of ILI were reported,with an ILI％of 4.70％.ILI％among different years presented statistically significant differences(P＜0.001).People aged 0-14 years old were the main population with ILI,accounting for 82.90％.The positive rate of influenza virus in ILI specimens was 14.14％,the positive rate of influenza virus among diffe-rent years and age groups were both significantly different(both P＜0.001).The main prevalent influenza strains from 2014 to 2023 included types A(H1N1),A(H3N2),B(Victoria),and B(Yamagata),alternating among di-fferent years.However,type B(Yamagata)strains were not detected from 2020 to 2023.There were basically two influenza prevalence seasons every year,namely winter-spring and summer.Conclusion People＜15 years old are the main population of influenza,and the prevalence peaks are in winter-spring and summer.From 2021 to 2023,the prevalence alternates mainly among 3 types:A(H1N1),A(H3N2),and B(Victoria).

This study was aimed at creating an engineered strain of Bacillus subtilis for efficient expression of biologically active type 2 toxin B(TcdB2)derived from a highly virulent strain of Clostridium difficile.The TcdB2 gene was cloned from ST1/RT027 strain genome DNA,incorporated into the PHT01 vector,and then transformed into B.subtilis strain WB800N for prokaryotic expression.Cell toxicity assays revealed that the recombinant TcdB2 exhibited cytotoxic effects in various cells.The engineered B.subtilis strain effectively expressed biologically active TcdB2,thus providing a basis for further exploration of the pathogenic mechanisms of highly virulent strains of C.difficile and establishing a foundation for potential vaccine can-didate targets.

Ketamine,an antagonist of the glutamate N-methyl-D-aspartate(NMDA)receptor,is cur-rently one of the most widely abused psychoactive substances.Prolonged abuse can result in damages to various systems in the body,making it crucial to investigate the regulatory mechanism of ketamine addic-tion and screening related biomarkers.In this study,zebrafish embryos/larvae were initially exposed a-cutely to ketamine.Then,a ketamine addiction model was established in 6-month-old zebrafish through conditioned place preference(CPP)experiments.The zebrafish brain transcriptome was analyzed using RNA-seq,while qPCR and Western blotting were employed to detect the expression of key genes.Results revealed significant reductions in the spontaneous tail coiling,embryo hatching rate,and survival rate of zebrafish embryos in the ketamine-treated group compared to the control group.The distance moved also decreased significantly,from 1904.2 mm in the control group to 319.0 mm in the high dose of ketamine group(300 μmol/L).Conditional positional preference experiments demonstrated that the control ze-brafish did not exhibit significant changes in activity in the CPP tank.In contrast,the ketamine-treated group increased their activity time in the light zone of the tank from 385.2 s before training to 706.4 s af-ter training,representing a 26.8％increase(***P＜0.001).This suggests a preference for ketamine stimulation in zebrafish.KEGG analysis indicated enrichment of differentially expressed genes in the neu-roactive ligand-receptor interaction pathway in the ketamine-treated samples.GSEA analysis further re-veals a significant upregulation of the glutamatergic synapse pathway(NES=1.5).In addition,compared with the control group,the mRNA levels of Grin2b and Gria2 in the ketamine group increased by 4.6 and 1.4 times,respectively,while the protein levels increased by 2.0 and 1.4 times,respectively.These findings suggest that ketamine can induce addiction in zebrafish,potentially through upregulation of the glutamatergic synaptic pathway.

Objective:To compare the clinical efficacy of ultrasound-guided spinal nerve block (SNB) and paraverteral nerve block (PVB) in treating postherpetic neuralgia.Methods:A total of 52 patients with postherpetic neuralgia who visited the Pain Clinic of the Xiangya Hospital, Central South University from February 2020 to December 2022 were selected and randomly divided into an ultrasound-guided SNB group and a PVB group using a random number table method, with 26 patients in each group. Patients in the SNB group received ultrasound-guided spinal nerve block therapy; The PVB group received ultrasound-guided paraverteral nerve block treatment. Visual Analog Scale (VAS) scores, 36-Item Short Form Survey (SF-36) scores, and total effective rate were observed in two groups of patients before treatment, 2 weeks after treatment, 1 month after treatment, 3 months after treatment, and 6 months after treatment. Complications during treatment were also observed.Results:The total effective rates of SNB group patients at 1, 3, and 6 months after treatment were significantly higher than those of PVB group (all P<0.05). After treatment, the VAS scores of both groups of patients at each time point were significantly reduced compared to before treatment (all P<0.05); The VAS scores of patients in the SNB group were lower than those in the PVB group at 1, 3, and 6 months after treatment, but the difference was not statistically significant (all P>0.05). There was no statistically significant difference in Physical Component Summary (PCS) and Mental Component Summary (MCS) scores between SNB and PVB groups before nerve block treatment (all P>0.05). The MCS and PCS scores of the two groups of patients were significantly higher than before treatment at 2 weeks, 1 month, 3 months, and 6 months after treatment (all P<0.05). The MCS scores of the SNB group were significantly higher than those of the PVB group at 2 weeks, 1 month, 3 months, and 6 months after treatment (all P<0.05), but there was no statistically significant difference in PCS scores between the two groups (all P>0.05). Both groups of patients did not experience any serious complications related to the treatment in this study during the follow-up period. Conclusions:Both ultrasound-guided spinal nerve block and paraverteral nerve block can safely and effectively treat postherpetic neuralgia. The clinical effect of ultrasound-guided spinal nerve block in treating postherpetic neuralgia is better than that of paraverteral nerve block.

Objective:To compare the efficacy of Kirschner wire fixation combined with Suture-Bridge technique and simple Kirschner wire fixation in the treatment of old lateral malleolar avulsion fractures under all-inside arthroscopy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 56 patients with old lateral malleolar avulsion fractures, admitted at Xuzhou Central Hospital from January 2018 to June 2022, including 32 males (32 feet) and 24 females (24 feet), aged 19-57 years [(35.2±11.1)years]. Twenty-five patients were treated with Kirschner wire fixation under all-inside arthroscopy (K-wire group), while the other 31 patients were treated with Kirschner wire fixation combined with Suture-Bridge technique under all-inside arthroscopy (K-wire combined with suture group). The surgical time, incision healing at 2 weeks after surgery, and fracture healing rate at 6 months after surgery of the two groups were detected. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores, and foot and ankle ability measure (FAAM) scores [including activities of daily living (ADL) scores and sports function (S) scores] of the two groups were assessed before surgery, at 3, 6 months after surgery, and at the last follow-up. The anterior drawer test was performed at 3, 6 months after surgery and at the last follow-up. The time of return to sports after surgery and complication rates were also recorded.Results:All the patients were followed up for 12-18 months [(14.2±2.2)months]. The surgical time in the K-wire combined with suture group was (56.3±12.5)minutes, longer than (41.1±8.2)minutes in the K-wire group ( P<0.01). The incisions in both groups were healed by first intention at 2 weeks after surgery. In the K-wire combined with suture group, all the fractures were healed at 6 months after surgery (100%), while in the K-wire group 22 patients (88%) obtained fracture healing ( P<0.05). There were no statistically significant differences in the AOFAS ankle-hindfoot scores, FAAM-ADL scores, or FAAM-S scores between the two groups preoperatively ( P>0.05). At 3, 6 months after surgery, and at the last follow-up, the AOFAS ankle-hindfoot scores in the K-wire combined with suture group were (89.7±3.4)points, (92.8±2.8)points, and (94.9±3.3)points respectively, higher than (87.4±4.4)points, (90.4±4.1)points, and (92.5±4.6)points in the K-wire group ( P<0.05); the FAAM-ADL scores and the FAAM-S scores in the K-wire combined with suture group were (90.1±3.5)points, (91.5±2.9)points, (92.8±3.0)points and (91.4±5.4)points, (92.8±5.0)points, (94.4±4.8)points respectively, higher than (86.8±5.0)points, (88.7±3.8)points, (90.3±3.7)points and (88.0±5.3)points, (89.5±4.8)points, (91.5±5.2)points ( P<0.05 or 0.01). The AOFAS ankle-hindfoot scores, FAAM-ADL scores, and FAAM-S scores at all postoperative time points were higher than those preoperatively and increased with the passage of the follow-up time ( P<0.01). The results of the anterior drawer test at all postoperative time points in the two groups were negative. The time of return to sports after surgery in the K-wire combined with suture group was (9.2±1.3)weeks, shorter than (10.3±1.5)weeks in the K-wire group ( P<0.01). One patient (3.2%) in the K-wire combined with suture group and 3 patients (12.0%) in the K-wire group had Kirschner wire loosening and withdrawal ( P>0.05). Neither of the two groups developed complications such as nerve or tendon injuries. Conclusion:Compared with simple Kirschner wire fixation under all-inside arthroscopy, Kirschner wire fixation combined with Suture-Bridge technique under all-inside arthroscopy achieves higher fracture healing rate, more obvious improvement in life quality and ankle function, as well as earlier return to sports in the treatment of old lateral malleolar avulsion fractures.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To prospectively observe the changes of tumor-related symptoms in patients with nasopharyngeal carcinoma following the administration of nimotuzumab one week before radiotherapy.Methods:Non-metastatic nasopharyngeal carcinoma patients with positive epidermal growth factor receptor (EGFR) expression and symptoms caused by the primary lesion or metastatic cervical lymph nodes admitted to Cancer Hospital of Chinese Academy of Medical Sciences were prospectively recruited. Investigators recorded tumor-related symptoms in recruited patients one day before the first administration of nimotuzumab (D0) and conducted follow-up visits from day 2 to day 7 after the first administration (D2-D7) to document symptom changes. All recruited patients were asked to assess tumor-related symptoms on D0 and D7 by visual analogue scale (VAS) scores. VAS scores were analyzed by paired t-test. Results:From June 2020 to April 2023, a total of 21 patients met the inclusion criteria. The median age was 49 years (range: 27-69 years), with a male-to-female ratio of 1.3:1. Among the patients, 17 patients (81%) received concurrent nimotuzumab for 8 cycles, 7 cycles for 3 cases (14%), and 6 cycles for 1 case (5%), respectively. All patients completed symptom assessments as required. The overall response rate of symptoms after the first administration of nimotuzumab was 62%, with response rates of 4/6、5/8、4/10、4/10、4/11、3/11 for tinnitus, headache, aural fullness, secondary pain caused by neck mass, nasal bleeding, and nasal obstruction, respectively. The VAS scores for overall symptoms were significantly decreased after the administration of nimotuzumab one week before radiotherapy ( P<0.001), with the most significant decrease in VAS scores for tinnitus, aural fullness, and headache. Conclusion:The administration of nimotuzumab one week before radiotherapy significantly alleviates tumor-related symptoms in patients with nasopharyngeal carcinoma, particularly in alleviating tinnitus, aural fullness, and headache.

Objective:To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China.Methods:Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 μg/g·creatinine, middle:0.77-1.69 μg/g·creatinine, high:≥1.69 μg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model.Results:The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) μg/g·creatinine, and the BMI was (22.70±3.82) kg/m 2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 μg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m 2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI ( Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference ( Plinear<0.001), hip circumference ( Plinear<0.001), and calf circumference ( Plinear<0.001). Conclusion:Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.