Caenorhabditis elegans,as an emerging model organism,has been widely used in multiple disciplines such as medicine,life science,and environmental science in recent years,due to its charac-teristics of short life cycle,clear genetic background,highly conserved evolution,complete genome analysis and excellent fitting between experimental data and human results.It also shows unique advan-tages in the field of toxicology.This paper summarizes its advantages in toxicological research starting from the biological characteristics of C.elegans,introduces the toxicological research methods and progress based on the C.elegans model,focuses on demonstrating its applications in environmental fo-rensic medicine and forensic toxicology,and looks forward to the application of the relevant results in the field of forensic science.

Objective:To investigate the prognosis of postoperative adjuvant therapy for hepatocellular carcinoma after conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 103 patients with initially unresectable hepatocellular carcinoma (HCC) who were admitted to 11 medical centers in China, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from November 2019 to May 2023 were collected. There were 83 males and 20 females, aged (54±12)years. All 103 patients underwent conversion therapy of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) successfully followed by sequential hepatectomy, of which 72 patients undergoing postoperative adjuvant therapy were divided into the adjuvant therapy group, and 31 patients undergoing postoperative follow-up monitoring were divided into the follow-up monitoring group. Observation indicators: (1) follow-up and postoperative condi-tions; (2) analysis of factors influencing recurrence-free survival time of patients; (3) stratified ana-lysis. Comparison of count data between group was conducted using the chi-square test or Fisher exact probability. The R software was used to draw survival curves, and the Log-rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Results:(1) Follow-up and postoperative conditions. All 103 patients were followed up for 21.0(range, 1.9?47.2)months, with the median recurrence-free survival time of 28.7 months and the 1-, 2-, 3-year recurrence-free survival rates of 68.6%, 55.6%, 41.2%. The median overall survival time of 103 patients was unreached, and the 1-, 2-, 3-year overall survival rates were 90.9%, 82.1%, 69.6%, respectively. The median recurrence-free survival time was 33.1 months in patients of the adjuvant therapy group, with the 1-, 2-year recurrence-free survival rates as 77.2%, 61.5%. The median recurrence-free survival time was 11.1 months in patients of the follow-up monitoring group, with the 1-, 2-year recurrence-free survival rates as 46.6%, 40.8%. There was a significant difference in recurrence-free survival between the two groups of patients ( χ2=5.492, P<0.05). (2) Analysis of factors influencing recurrence-free survival time of patients. Results of multivariate analy-sis showed that pathologic complete response and postoperative adjuvant therapy were independent factors influencing recurrence-free survival time of HCC patients undergoing conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy ( hazard ratio=0.297, 0.492, 95% confidence interval as 0.137?0.647, 0.268?0.903, P<0.05). (3) Stratified analysis. Of the 71 patients with non-pathologic complete response, the median recurrence-free survival time of 48 patients in the adjuvant therapy group was 24.0 months, with the 1-, 2-year recurrence-free survival rates as 67.4%, 48.8%. The median recurrence-free survival time of 23 patients with non-pathological complete response in the follow-up monitoring group was 7.4 months, with the 1-, 2-year recurrence-free survival rates as 35.0%, 26.3%. There was a significant difference in recurrence-free survival between the 48 patients with non-pathologic complete response in the adjuvant therapy group and the 23 patients with non-pathologic complete response in the follow-up monitoring group ( χ2=5.241, P<0.05). Conclusion:For HCC patients with conversion therapy of TKIs and ICIs followed by sequential hepatectomy, postoperative adjuvant therapy, compared to postoperative follow-up monitoring, can prolong the recurrence-free survival time of patients, of whom cases with non-pathologic complete response can benefit from adjuvant therapy.

Objective:To investigate the prognosis of postoperative adjuvant therapy for hepatocellular carcinoma after conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 103 patients with initially unresectable hepatocellular carcinoma (HCC) who were admitted to 11 medical centers in China, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from November 2019 to May 2023 were collected. There were 83 males and 20 females, aged (54±12)years. All 103 patients underwent conversion therapy of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) successfully followed by sequential hepatectomy, of which 72 patients undergoing postoperative adjuvant therapy were divided into the adjuvant therapy group, and 31 patients undergoing postoperative follow-up monitoring were divided into the follow-up monitoring group. Observation indicators: (1) follow-up and postoperative condi-tions; (2) analysis of factors influencing recurrence-free survival time of patients; (3) stratified ana-lysis. Comparison of count data between group was conducted using the chi-square test or Fisher exact probability. The R software was used to draw survival curves, and the Log-rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Results:(1) Follow-up and postoperative conditions. All 103 patients were followed up for 21.0(range, 1.9?47.2)months, with the median recurrence-free survival time of 28.7 months and the 1-, 2-, 3-year recurrence-free survival rates of 68.6%, 55.6%, 41.2%. The median overall survival time of 103 patients was unreached, and the 1-, 2-, 3-year overall survival rates were 90.9%, 82.1%, 69.6%, respectively. The median recurrence-free survival time was 33.1 months in patients of the adjuvant therapy group, with the 1-, 2-year recurrence-free survival rates as 77.2%, 61.5%. The median recurrence-free survival time was 11.1 months in patients of the follow-up monitoring group, with the 1-, 2-year recurrence-free survival rates as 46.6%, 40.8%. There was a significant difference in recurrence-free survival between the two groups of patients ( χ2=5.492, P<0.05). (2) Analysis of factors influencing recurrence-free survival time of patients. Results of multivariate analy-sis showed that pathologic complete response and postoperative adjuvant therapy were independent factors influencing recurrence-free survival time of HCC patients undergoing conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy ( hazard ratio=0.297, 0.492, 95% confidence interval as 0.137?0.647, 0.268?0.903, P<0.05). (3) Stratified analysis. Of the 71 patients with non-pathologic complete response, the median recurrence-free survival time of 48 patients in the adjuvant therapy group was 24.0 months, with the 1-, 2-year recurrence-free survival rates as 67.4%, 48.8%. The median recurrence-free survival time of 23 patients with non-pathological complete response in the follow-up monitoring group was 7.4 months, with the 1-, 2-year recurrence-free survival rates as 35.0%, 26.3%. There was a significant difference in recurrence-free survival between the 48 patients with non-pathologic complete response in the adjuvant therapy group and the 23 patients with non-pathologic complete response in the follow-up monitoring group ( χ2=5.241, P<0.05). Conclusion:For HCC patients with conversion therapy of TKIs and ICIs followed by sequential hepatectomy, postoperative adjuvant therapy, compared to postoperative follow-up monitoring, can prolong the recurrence-free survival time of patients, of whom cases with non-pathologic complete response can benefit from adjuvant therapy.

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

Objective: To analyze the epidemiological characteristics, etiology and hemagglutinin (HA) gene characteristics of prevalent strains in Shandong Province from 2021 to 2022. Methods: The sentinel surveillance data of influenza-like illness (ILI) were collected in Shandong Province from 2021 to 2022. ILI specimens were detected with Real-Time PCR and virus isolation to explore the distribution of influenza viruses in different months. Three virus strains of each city were selected for gene sequencing, and the HA phylogenetic analysis was carried out. Results: In the surveillance-year from 2021 to 2022, 528 263 ILI cases were totally reported in 54 sentinel hospitals for influenza surveillance in Shandong Province. ILI visiting ratio (ILI%) was 4.07%, with the largest number in 0-4 age group (45.86%). The highly frequent season for ILI was in winter and spring, with a peak in the 52nd week, 2021 (6.62%). Totally, nucleic acid was detected in 26 754 specimens, with a positive rate of 27.10%, all of which were type B Victoria influenza. The positive rate reached a peak in the 49th week, 2021 (63.78%). A total of 295 outbreaks of ILI had been reported, in which 269 were positive for influenza virus. Most of outbreaks occurred in the primary school, with a peak in December. Gene evolution analysis showed that the HA gene in Shandong possessed high homology, 98.6% to 99.5%, with the recommended vaccine strains in 2020-2023, which was divided into two branches, V1A.3a.1 and V1A.3a.2. Conclusion: In the surveillance-year of 2021-2022, influenza is prevalent in December in Shandong Province, with a single circulating strain type. The positive rate of influenza virus and outbreak are higher than those in the previous surveillance-year. The circulating strain possesses high HA gene homology with those of the WHO vaccine recommended strains. However, the overall immune barrier of influenza virus is weak.
Humans ; Influenza, Human/prevention & control* ; Phylogeny ; Influenza Vaccines ; Orthomyxoviridae ; Seasons ; China/epidemiology* ; Virus Diseases

ObjectiveThe aim of this study is to investigate the proportion of DN2 cell and the correlation between the expression of calcium ion release activated calcium ion channel（ Ca²⁺ release-activated Ca²⁺， CRAC） protein in DN2 cells and the clinical activity of lupus nephritis （LN）. MethodsFlow cytometry was used to detect the proportion of DN2 cells in healthy controls （HC， n=15）， LN （HC， n=30）， rheumatoid arthritis （RA， n=15） and primary Sjogren syndrome （pSS， n=15） patients and the expression of SOCE protein Orai1 in DN2 cells. One-way ANOVA was used to analyze the differences among the four groups. The correlation between Orai1 expression and LN disease activity was analyzed by Pearson correlation analysis. ResultsThere was a statistically significant difference in the proportion of DN2 cells in peripheral blood among the four groups （F= 9.315， P＜0.000 1）. The proportion of DN2 cells in the peripheral blood of patients with LN was significantly higher than that of HC， RA and pSS ［（2.60±2.20）% vs.（0.68±0.56）% vs.（0.69±0.45）% vs.（1.04±0.72）%］ and was correlated with 24-hour urinary protein excretion （r=0.599 9， P=0.000 5）. There was a statistically significant difference in the Orai1 expression in DN2 cells among the four groups （F= 7.935， P＜0.000 1）. The Orai1 expression in DN2 cells of LN was significantly higher than that of HC， RA and pSS （2.30±1.50 vs. 0.86±0.39 vs. 1.34±0.57 vs. 1.13±0.64）. Orai1 expression in DN2 cells was positively correlated with SLEDAI （r=0.56， P＜0.005）， blood anti-dsDNA antibody level （r=0.43， P＜0.05） and 24-hour urinary protein excretion （r=0.44， P＜0.05）， and negatively correlated with complement C3 （r=-0.39， P＜0.05）. ConclusionsThe proportion of DN2 cells and the expression of Orai1 increases in patients with LN and is correlated with disease activity. SOCE of DN2 cells may be a potential therapeutic target for LN.

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd

ObjectiveThe aim of this study is to investigate the proportion of DN2 cell and the correlation between the expression of calcium ion release activated calcium ion channel（ Ca²⁺ release-activated Ca²⁺， CRAC） protein in DN2 cells and the clinical activity of lupus nephritis （LN）. MethodsFlow cytometry was used to detect the proportion of DN2 cells in healthy controls （HC， n=15）， LN （HC， n=30）， rheumatoid arthritis （RA， n=15） and primary Sjogren syndrome （pSS， n=15） patients and the expression of SOCE protein Orai1 in DN2 cells. One-way ANOVA was used to analyze the differences among the four groups. The correlation between Orai1 expression and LN disease activity was analyzed by Pearson correlation analysis. ResultsThere was a statistically significant difference in the proportion of DN2 cells in peripheral blood among the four groups （F= 9.315， P＜0.000 1）. The proportion of DN2 cells in the peripheral blood of patients with LN was significantly higher than that of HC， RA and pSS ［（2.60±2.20）% vs.（0.68±0.56）% vs.（0.69±0.45）% vs.（1.04±0.72）%］ and was correlated with 24-hour urinary protein excretion （r=0.599 9， P=0.000 5）. There was a statistically significant difference in the Orai1 expression in DN2 cells among the four groups （F= 7.935， P＜0.000 1）. The Orai1 expression in DN2 cells of LN was significantly higher than that of HC， RA and pSS （2.30±1.50 vs. 0.86±0.39 vs. 1.34±0.57 vs. 1.13±0.64）. Orai1 expression in DN2 cells was positively correlated with SLEDAI （r=0.56， P＜0.005）， blood anti-dsDNA antibody level （r=0.43， P＜0.05） and 24-hour urinary protein excretion （r=0.44， P＜0.05）， and negatively correlated with complement C3 （r=-0.39， P＜0.05）. ConclusionsThe proportion of DN2 cells and the expression of Orai1 increases in patients with LN and is correlated with disease activity. SOCE of DN2 cells may be a potential therapeutic target for LN.

Stellera chamaejasme L. is a traditional Chinese medicine with a long history to treat stubborn skin ulcer, and it also has antiviral and antitumor effects. Neochamaejasmine B (NCB), Neochamaejasmine A (NCA) and Chamaechromone (CMC) are the major components in dried roots of Stellera chamaejasme L.. Our studies suggested that NCB, NCA and CMC are inhibitors of Organic anion transporter 1 (OAT1). OAT1 is encoded by solute carrier family 22 member 6 gene (SLC22A6) in humans and plays a critical role in the organic anion drug uptake and excretion in the kidney. Lamivudine is the typical substrate of OAT1 and is frequently used in combination with other antiviral drugs in clinical antiviral treatments. The aim of this study is to investigate the interaction and its mechanism between these bi-flavone components in Stellera chamaejasme L. and lamivudine via OAT1 both in vitro and in vivo. In vitro, the uptake studies in Madin-Darby canine kidney (MDCK) cells overexpressing OAT1 suggested that NCB inhibited the uptake of 6-CFL and lamivudine.Similar results were obtained for NCA and CMC. NCB was a noncompetitive and competitive inhibitor interaction with OAT1. IC values of NCB, NCA and CMC for inhibiting OAT1-mediated lamivudine transport were 2.46, 8.35 and 0.61 μmol·L, respectively. In vivo, the pharmacokinetic results of lamivudine in rats showed that the mean area under the plasma concentration-time curve (AUC) and maximal plasma concentration (C) of lamivudine after co-administration is increased 2.94-fold and 1.87-fold, respectively, compared to lamivudine administration alone. The results of interactions between lamivudine and these bi-flavone components in Stellera chamaejasme L. extracts via OAT1 in vivo are consistent with studies in vitro. The inhibition of OAT1-mediated uptake of lamivudine by NCB, NCA and CMC is the possible mechanism for Stellera chamaejasme L. extracts improving the oral bioavailability of lamivudine in rats.

Objective: To explore the clinical effects of the reconstruction of extensive leg defects using the free anterolateral thigh flap with the contralateral leg vessels as the recipient vessels. Methods: From January 2012 to January 2018, ten patients were treated with severe and extensive leg defects in the department of orthopedics of the First Affiliated Hospital of Nanchang University. There were 7 males and 3 females with an average age of 35, from 17 to 56. There were no main vessels for angiogenesis around the wounds in all cases. The size of defects ranged from 20 cm×13 cm to 29 cm×15 cm. The position of defects were anterior of shank in 5 cases, medial in 3 cases and medial posterior in 2 cases. The various flaps were harvested from the anterolateral thigh region of healthy leg and transferred to repair the leg defects. The healthy vessels of the contralateral leg were chosen as the recipient vessels. The musculocutaneous flap, fascia flap or perforator was removed according to the size of the defect and whether it was necessary to fill the dead space of the wound. The limbs were placed in parallel position and was fixed by external fixator. The pedicle division training was started 1 week after operation, the period of pedicle division and external fixator removing was from 21 days to 32 days. When the pedicle was divided, the vascular end of the limb and the distal end were anastomosed to re-established the continuous vessels. Results: All 10 flaps survived completely after surgery. The size of flaps ranged from 23 cm×14 cm to 32 cm×16 cm. The recipient vessels that were used included the posterior tibial vessels in 5 cases and anterior tibial vessels in the remaining 5 cases. All the vessels in flap pedicle were anastomosed to the recipient vessels in an end-to-end fashion. The anastomotic sites and vascular bundles were covered by using a local flap in 2 cases, skin tension reducer in 1 cases, and free skin graft in the remaining 7 cases. Very mild infection occurred in one case and was controlled by dress changing. A small-sized necrosis of the grafted skin occurred in another patient. All patients were followed up for 6 to 18 months with an average of 12 months. The function of the lower extremities almost recovered. All patients were happy with the final functional and aesthetic outcomes. Conclusions Although there some drawbacks of the technique, such as long-term immobilization of the lower extremities, multiple staged surgeries, for strictly selected patients, the healthy vessels of the contralateral leg could be served as recipients vessels when a free myocutaneous, fasciocutaneous, or perforator flap was used to reconstruct the extensive and severe injury of the leg, particularly in the absence of usable vessels in the ipsilateral leg.