Objective To investigate the effect of tritiated water on the immune system of zebrafish and its potential molecular mechanism. Methods Zebrafish embryos (2.5 to 3 hours post-fertilization [hpf]) were exposed to 3.7 × 10⁴ Bq/mL tritiated water (tritiated water group), and those exposed to E3 culture medium were used as the control group. The mortality rate, hatching rate, deformity rate, heart rate, body length, yolk sac area, neutrophil count in the tail, immune-related gene expression, and immune-related protein expression of zebrafish in the two groups were determined. Then transcriptome technology was used to further analyze the possible mechanism of tritiated water affecting the immune system of zebrafish. Results Compared with the control group, zebrafish at 72 hpf in the tritiated water group had no significant changes in the mortality rate, hatching rate, deformity rate, body length, and yolk sac area((t = 0.9045, 0.5000, 1.0000, 0.7238, 0.0337, P = 0.4169, 0.6433, 0.3739, 0.4785, 0.9735), but had significantly increased heart rate(t = 4.575，P = 0.002). At 4 days post-fertilization (dpf), the neutrophil count in the tail of zebrafish in the tritiated water group was significantly increased(t = 2.563，P = 0.0196), the mRNA expression of TNF-α was significantly decreased(t = 2.891, P = 0.045), the protein expression of nuclear factor-kappa B (NF-κB) was significantly increased(t = 3.848, P = 0.018), and the protein expression of NLRP3 was significantly decreased(t = 14.98, P = 0.001). At 7 dpf, the neutrophil count in the tail and the protein expression levels of NF-κB, NLRP3, and interleukin-1β were significantly decreased(t = 3.772, 7.048, 15.620, 4.423, P = 0.014, 0.002, 0.0001, 0.012). Transcriptome sequencing revealed that differentially expressed genes were mainly enriched in the “neutrophil activation” and “platelet activation pathways” at 4 dpf and in the “neutrophil apoptosis”, “ferroptosis”, and “necroptosis” pathways at 7 dpf. Conclusion Tritiated water exposure induces a temporally dynamic immune response in zebrafish, potentially affecting immune homeostasis by regulating neutrophil activation and apoptosis, as well as the expression of NF-κB and NLRP3.

Objective:To explore the technical focus of robotic-assisted laparoscopic surgery for the treatment of horseshoe kidney combined with renal tumor.Methods:The clinical data of a patient with horseshoe kidney combined with renal tumor treated by robot-assisted laparoscopic partial nephrectomy in the Second Hospital of Dalian Medical University in September 2021 were retrospectively analyzed. PubMed, CNKI, Wanfang and VIP databases were searched for all the literature on the use of robot-assisted laparoscopic nephrectomy or partial nephrectomy for the treatment of horseshoe kidney combined with renal tumor from the time of establishment to December 2022.Results:A total of 11 patients from 10 articles were retrieved and 12 patients were enrolled. Among the 12 patients, 4 cases used the retroperitoneal approach and 8 cases used the transperitoneal approach. Two cases were operated by traditional laparoscope, and the arteries were searched for and controlled before the robotic arm was placed to perform the partial nephrectomy and suture; and 10 cases were operated with the robotic-assisted laparoscopic approach throughout the whole procedure. Five cases of nephrectomy were performed on one side, and 7 cases were performed in the partial nephrectomy. Postoperative pathological diagnosis was clear cell carcinoma in 8 cases, chromophobe cell carcinoma in 1 case, eosinophilic cell carcinoma in 1 case, renal cell carcinoma in 1 case, and renal abscess in 1 case. The patient in the Second Hospital of Dalian Medical University was 38 years old female who was admitted to the hospital with a fever. After CT arteriography and three-dimensional reconstruction, robotic-assisted laparoscopic partial nephrectomy of right kidney and isthmus dissecting was performed. During the operation, tumor trophoblast vessels were ligated and dissected one by one by using single-use tissue closure clips, and the isthmus was dissected using endoscopic cutting anastomosis on the left side of the tumor, with the tumor edges sharply resected and completely dissected. The operation time was 240 min, without thermal ischemia time, and the bleeding volume was about 300 ml. The patient recovered well after the operation, and the postoperative pathological diagnosis was renal abscess.Conclusions:Robot-assisted laparoscopic treatment of horseshoe kidney combined with renal tumor is safe and effective, and has more advantages than traditional laparoscopic surgery. Preoperative CT arteriography or three-dimensional reconstruction examination should be applied to fully evaluate the variant vessels. The surgical access and plan should be decided according to the size and location of the tumor. The variant vessels should be properly handled during operation. The use of endoscopic cutting anastomosis to deal with the isthmus can be more conducive to the surgical operation.

Objective:To explore the relevant risk factors and prognosis of patients with intrahepatic cholangiocarcinoma (ICC) who experienced recurrence within 6 months after surgeryMethods:This retrospective study included a total of 259 patients with ICC a treated at He'nan Provincial People's Hospital and He'nan Cancer Hospital from Jan 2018 to Jan 2020. The clinical and pathological data ,differences between the group with recurrence within 6 months and the group without recurrence within 6 months were compared using the chi-square test. Logistic regression analysis was used to determine the relevant risk factors for recurrence within 6 months. Kaplan-Meier method was used to construct survival and recurrence curves, and survival rates were calculated.Results:The overall survival and recurrence-free survival of patients in the group with recurrence within 6 months were significantly shorter. CA19-9, tumor longitudinal diameter, microvascular invasion, and neural invasion were identified as independent risk factors for recurrence within 6 months after ICC surgery ( P<0.001). Conclusion:The patient population experiencing recurrence within 6 months after ICC surgery has an extremely poor prognosis and possesses a specific tumor microenvironment. CA19-9, tumor longitudinal diameter, microvascular invasion, and neural invasion were identified as independent risk factors for recurrence within 6 months after ICC surgery.

Objective To explore the protective effect in a model of nicotinamide riboside(NR)against carbonyl cyanide m-chlorophenylhydrazone(CCCP)-induced oxidative stress in R28 cells.Methods 4 μmol/L CCCP was used to induce oxidative stress in R28 cells,and 400 nmol/L NR was used to intervene.The cell viability was quantified by CCK-8 assay.The apoptosis was detected by Annexin-V/PI double staining and flow cytometry.Western blotting was used to examine the levels of Cytochrome C,Caspase-3,and Caspase-9 to evaluate the apoptosis.Tetramethylrhodamine ethyl ester was used to detect the mitochondrial membrane potential(MMP),MitoSOX was used to detect the mitochondrial reactive oxygen species(mtROS)levels,and adenosine triphosphate(ATP)assay kit was used to assess ATP generation ability to evaluate mitochondrial function.Results After CCCP treatment of R28 cells,the cell viability decreased,the apoptotic protein levels and apoptosis rates increased,the MMP decreased,and the mtROS generation increased(P＜0.05).After NR pretreatment,the cell viability increased,the apoptotic protein levels and apoptosis rates decreased,the MMP increased,and the mtROS generation decreased(P＜0.05).Conclusion:NR enhances the cell viability,reduces the expression of apoptotic proteins,and ultimately reduces the apoptosis of retinal ganglion cell by inhibiting oxidative stress response and protecting mitochondrial function.

Objective To investigate the therapeutic mechanism of Gandou Bushen Decoction(GDBSD)for improving reproductive disorders in male mouse models of Wilson disease(WD).Methods Sixty male homozygous TX mice were randomized equally into 4 groups and treated with daily gavage of saline(WD model group),penicillamine(0.09 g/kg),or GDBSD(0.2 mL/10 g),or with intraperitoneal injection of U0126(20 mg/kg)in addition to GDBSD gavage,with 15 male DL mice as control.After 4 weeks of treatment,copper content in testicular tissue of the mice was detected,and histopathology of the testes and epididymis was examined using HE staining and electron microscopy.TUNEL staining was used to identify apoptotic cells in the testes.The protein expressions of Bcl-2,Cytc,caspase-3,ERK,and p-ERK in the testicular tissue were evaluated with Western blotting,and BrdU-positive cells were detected with immunohistochemical labeling.Sperm density,viability,malformation rate and fertility levels of male mice were studied.Results Treatment with penicillamine and GDBSD obviously improved pathological changes of the testis,increased sperm density and motility,lowered sperm abnormality rate,fertility levels and increased testicular JOHNSEN score of TK mice,but the therapeutic effect of GDBSD was blocked by U0126.GDBSD treatment significantly lowered Cytc and caspase-3 expressions and increased Bcl-2 expression in the testicular tissue of TX mice(P<0.05),while U0126 treatment significantly lowered testicular Bcl-2 expression level.No significant differences were found in total protein expression levels of ERK1/2 among the 5 groups,but p-ERK protein expression was significantly reduced in WD and U0126 groups and increased in penicillamine and GDBSD groups.Conclusion GDBSD can improve spermatogenesis and enhance fertility of male TX mice with WD possibly by activating the ERK signaling pathway to enhance proliferation and reduce apoptosis of the spermatogenic cells.

Objective:To summarize the clinical characteristics and factors that may affect the flare of patients with systemic lupus erythematosus (SLE).Methods:A total of 300 patients with SLE who were treated with standard treatment in the outpatient clinic of the department of rheumatology and immunology of the Second Affiliated Hospital of Air Force Military Medical University of PLA, were enrolled, and the patients were divided into 24 patients in the complete response group, 40 cases in the no response group, 192 cases in the treatment response group, and 44 cases in the low disease activity group according to the response to treatment. The differences in clinical characteristics and survival rates between the groups were compared and analyzed. Comparisons of count data were made using analysis of variance (ANOVA), comparisons of measurement data were made using the chi-square test or the Fisher′s ecact test, and survival rates were expressed as Kaplan-Meier curves. Cox regression analysis was adapted to explore risk factors for flare in these patients.Results:A total of 300 patients were followed. With a median follow-up time of 18 (1, 36) months, a total of 42 patients experienced flare. The clinical characteristics of the four groups were compared, and there were significant differences in age ( F=4.39, P=0.005), the presence of lupus nephritis ( χ2=12.66, P=0.005), hemoglobin level ( F=2.73, P=0.044), NLR level( F=3.88, P=0.010), cystatin C level( F=3.11, P=0.027), anti-RNP antibody ( χ2=12.04, P=0.007), anti-Sm antibody ( χ2=8.33, P=0.040), anti-SSB antibody ( P=0.014), anti-nucleosome antibody ( P=0.014), and anti-ribosomal P protein antibody ( χ2=11.83, P=0.008). There was no significant difference in survival between the four groups. Cox analysis showed that the combination of other autoimmune diseases [ HR(95%CI)=3.23(1.58, 6.57), P=0.001], anti-Sm antibody [ HR(95%CI)=2.15(1.04, 4.43), P=0.038], and anti-RNP antibody [ HR(95%CI)=2.54(1.13, 5.68), P=0.023] were risk factors for flare in patients with SLE who could reach the treatment target. Conclusion:Patients with SLE with different treatment responses have different clinical features, and all treatment can significantly improve the recurrence rate no matter what level of response to treatment. Patients concurrent with other autoimmune diseases, positive anti-Sm antibodies, and positive anti-RNP antibodies are at highrisk of flare.

Objective: To assess the exposure levels of lead, cadmium, mercury, arsenic and aluminum in the diets of residents in Henan Province, so as to provide the basis for strengthening food safety supervision. Methods: Six sampling points were selected using stratified random sampling method in Henan Province, including Hebi City, Xiangfu District of Kaifeng City, Jianxi District of Luoyang City, Yuzhou City, Baofeng County and Tanghe County. Food samples were collected and processed into mixed samples of 12 major food categories. The levels of lead, cadmium, mercury, arsenic and aluminum in the samples were measured using inductively coupled plasma mass spectrometry (ICP-MS). Dietary consumption information in Henan Province was collected. The dietary exposure risks of lead, cadmium, mercury, arsenic and aluminum were analyzed using the point estimation method and distribution point estimation method, based on the health guidance values of the Joint FAO/WHO Expert Committee on Food Additives and the margin of exposure (MOE) as the assessment criteria. Results: The dietary exposure level of lead among residents in Henan Province was 41.89 μg/d, which was equivalent to 18.62% of its provisional tolerable weekly intake (PTWI), with cereals and vegetables being the main sources; the MOE values of lead among residents aged 2 to <7 years and 7 to <13 years were both less than 1. The dietary exposure level of cadmium was 10.79 μg/d, which was equivalent to 20.55% of the provisional monthly tolerable intake, with cereals and vegetables being the main sources. The dietary exposure level of total mercury was 0.45 μg/d, which was equivalent to 1.25% of its PTWI, with cereals, vegetables, and water and beverage categories being the main sources; the dietary exposure level of methylmercury was 0.04 μg/d, which was equivalent to 0.28% of its PTWI, and it was entirely derived from aquatic products. The dietary exposure level of total arsenic was 26.65 μg/d, which was equivalent to 0.89% of the daily allowable intake, with cereals and vegetables being the main sources; the dietary exposure level of inorganic arsenic was 8.41 μg/d, which was equivalent to 6.23% of its PTWI, with an MOE value of 22.47. The dietary exposure level of aluminum was 8.27 mg/d, which was equivalent to 45.94% of its PTWI, with cereals and tubers being the main sources; the P90 and P97.5 of dietary aluminum exposure among residents aged 2 to <7 years and 7 to <13 years were both greater than PTWI. Conclusion The overall dietary exposure risks of lead, cadmium, mercury, arsenic and aluminum among residents in Henan Province are relatively low.

Laparoscopic right hemicolectomy is currently the most commonly used surgical procedure for right-sided colon cancer. Although this procedure is maturing in terms of key tech-niques such as the extent of surgical resection, the extent of lymph node dissection, and the recons-truction of digestive tract, it still lacks a standardized surgical procedure and quality control system. In the pre-preparation phase of the COLOR Ⅳ study (an international, multicenter, randomized contro-lled trail comparing the efficacy of intracorporeal anastomosis versus extracorporeal anasto-mosis in laparoscopic right hemicolectomy for right-sided colon cancer), the research team of the authors formulates a standardized procedure for laparoscopic right hemicolectomy based on the Delphi survey, and develops a competency assessment tool for surgical ability and quality. Attempts are being made to automate the evaluation of surgical techniques using artificial intelligence. It is hoped that the above work will help colorectal surgeons to standardize surgical operations and reduce complications, provide support for the homogenization of multicenter clinical studies, and promote the implementation of structured training for this procedure.

Objective:To investigate the specimen quality of intersphincteric resection with transabdominal transanal mixed approach for rectal cancer in the Chinese Transanal Total Mesorectal Excision Registry Collaborative (CTRC) database.Methods:The retrospective case-control study was conducted. Based on the concept of real-world research, the clinicopathological data of 281 pati-ents with rectal cancer in the CTRC database who underwent intersphincteric resection with trans-abdominal transanal mixed approach in 19 medical centers, including the Beijing Friendship Hospital of Capital Medical University et al, from November 15,2017 to December 31,2023 were collected. There were 196 males and 85 females, aged 61(range, 27-87)years. Observation indicators: (1) preoperative examinations; (2) neoadjuvant therapy; (3) postoperative examinations; (4) analysis of influencing factors for positive circumferential margin in surgical specimen of intersphincteric resec-tion for rectal cancer. Measurement data with normal distribution were represented as Mean±SD. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. The chi-square test was used for univariate analysis. Logistic regression model was used for multivariate analysis. Results:(1) Preoperative examinations. Of the 281 patients, 234 cases underwent preoperative pelvic magnetic resonance imaging (MRI) examina-tion. There were 2 cases in clinical stage T0, 3 cases in clinical stage T1, 58 cases in clinical stage T2, 137 cases in clinical stage T3, 24 cases in clinical stage T4, 3 cases in clinical stage Tx, 7 cases missing clinical T staging data. There were 87 cases in clinical stage N0, 68 cases in clinical stage N1, 60 cases in clinical stage N2, 9 cases in clinical stage Nx, 10 cases missing clinical N staging data. There were 30 cases with mesorectal fascia invasion, 53 cases with extramural venous invasion. The distance from lower margin of tumor to anal margin was 41.9(range, 1.0-80.0)mm. (2) Neoadjuvant therapy. Of the 281 patients, 125 cases underwent neoadjuvant therapy, including 39 cases receiving chemo-therapy alone, 6 cases receiving short-course simultaneous chemoradiotherapy, 5 cases receiving short-course simultaneous chemoradiotherapy and delayed surgery, 48 cases receiving long-course simultaneous chemoradiotherapy, 2 cases receiving other treatments, and 25 cases missing neoadju-vant therapy data. (3) Postoperative examinations. Of the 281 patients, 249 cases achieved R 0 resection, 9 cases achieved R 1 resection, and there were 23 cases missing surgical margin data. The maximum tumor diameter, the number of lymph nodes harvested and positive rate of vessel carcinoma embolus were 30.0(range, 0.5-200.0)mm, 13(range, 0-70) and 27.55%(73/265) in 281 patients. There were 252 patients with circumferential margin records, showing positive in 15 cases, with a positive rate as 5.95%(15/252). The minimum distance from deep part of tumor to circumferential margin was 7.0(range, 0-150.0)mm in 252 patients. There were 85 cases with distal margin records, showing positive in 1 case, and the distance from lower margin of tumor to distal margin was 10.0(range, 0-202.0)mm. There were 273 patients with specimen integrity records, which showed intact specimen in 208 cases, fair specimen in 58 cases, poor specimen in 4 cases, unevaluated specimen in 3 cases. There were 7 cases with rectal perforation. Of the 281 patients, cases in pathological stage T0, Tis, T1, T2, T3, T4 were 14, 5, 22, 107, 113, 12, respectively, and there were 8 cases missing pathological T staging data. Of the 281 patients, cases in pathological stage N0, N1a, N1b, N1c, N2a, N2b were 176, 27, 27, 11,20, 12, respectively, and there were 8 cases missing pathological N staging data. Of the 281 patients, there were 4 cases with distant metastasis, 262 cases without distant metastasis, 5 cases not evaluated, and 10 cases missing tumor metastasis data. Of the 125 patients undergoing neoadjuvant therapy, there were 85 cases with tumor regression grade records, including 16 cases as grade 1, 27 cases as grade 2, 19 cases as grade 3, 15 cases as grade 4, 8 cases as grade 5. (4) Analysis of influencing factors for positive circumferential margin in surgical specimen of intersphincteric resection for rectal cancer. Results of univariate analysis showed that preoperative T staging on preoperative pelvic MRI, mesorectal fascia invasion, extramural venous invasion, pathological T staging, and pathological N staging were related factors for positive circumferential margin in surgical specimen of intersphincteric resection for rectal cancer ( P<0.05). Conclusions:Intersph-incteric resection with transabdominal transanal mixed approach has good specimen quality and low positive rate of surgical margin. T staging on preoperative pelvic MRI may be related to positive circumferential margin after intersphincteric resection for rectal cancer.

Objective:To discuss the effect of NOD-like receptor protein 3(NLRP3)inflammasome on the renal interstitial fibrosis in the unilateral ureteral obstruction(UUO)model rats,and to clarify its potential mechanism.Methods:Thirty healthy male Wistar rats were randomly divided into sham operation group(n=6)and UUO group(n=24).The rats in sham operation group underwent the dissection of the ureter without ligation,while the rats in UUO group were sacrificed on the 3rd,7th,and 14th days after operation,and based on the treatment duration,the rats were divided into UUO 3 d group(n=8),UUO 7 d group(n=8),and UUO 14 d group(n=8).HE staining and Masson staining were used to observe the pathomorphology of kidney tissue of the rats in various groups;reagent kits were used to detect the levels of malondialdehyde(MDA),activities of superoxide dismutase(SOD),and levels of hydroxyproline(HYP)in kidney tissue of the rats in various groups;immunohistochemistry method was used to detect the expression levels of α-smooth muscle actin(α-SMA)and transforming growth factor-β1(TGF-β1)proteins in kidney tissue of the rats in various groups;Western blotting method was used to detect the expression levels of NLRP3 protein in kidney tissue of the rats in various groups.Results:The HE staining results showed significant tubular dilation,interstitial edema,and widening,with increased infiltration of inflammatory cells,and shedding of epithelial cells was seen in parts of the tubular lumina of the rats in UUO group.Compared with sham operation group,the interstitial fibrosis scores of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were significantly increased(P<0.05);compared with UUO 3 d group and UUO 7 d group,the interstitial fibrosis score of the rats in UUO 14 d group was significantly decreased(P<0.05).The Masson staining results showed that in UUO group,there was evident infiltration of inflammatory cells in the renal interstitium and a noticeable increase in fibrotic tissue proliferation;with the increasing of duration of UUO,some tubular structures disappeared,and the interstitial widened further with gradually increasing collagen deposition,particularly at the corticomedullary junction.Compared with sham operation group,the interstitial fibrosis scores of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were significantly increased(P<0.05);and compared with UUO 3 d and UUO 7 d groups,the interstitial fibrosis score of the rats in UUO 14 d group was significantly decreased(P<0.05).Compared with sham operation group,the levels of MDA in obstructed kidney tissue of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were significantly increased(P<0.05),and the SOD activities were significantly decreased(P<0.05).Compared with sham operation group,the levels of HYP in obstructed kidney tissue of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were also significantly increased(P<0.05);compared with UUO 3 d group,the level of HYP in obstructed kidney tissue of the rats in UUO 14 d group was significantly increased(P<0.05).The immunohistochemistry results showed that compared with sham operation group,the expression levels of α-SMA protein in kidney tissue of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were significant increased(P<0.05);compared with UUO 3 d and UUO 7 d groups,the expression levels of α-SMA protein in kidney tissue of the rats in UUO 14 d group was significantly increased(P<0.05);compared with sham operation group,the expression levels of TGF-β1 protein in renal tubular epithelial cells and renal tubule interstitial tissue of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were also significantly increased(P<0.05);compared with UUO 3 d group,the expression levels of TGF-β1 protein in the tubular epithelial cells and renal tubule interstitial tissue of the rats in UUO 14 d group were significantly decreased(P<0.05).The Western blotting results showed that compared with sham operation group,the expression levels of NLRP3 protein in kidney tissue of the rats in UUO 7 d and UUO 14 d groups were significantly increased(P<0.05).Conclusion:The NLRP3 inflammasome plays a critical role in renal fibrosis of the UUO rats,and its mechanism may be related to the increasing of oxidative stress and the increasing of expression level of TGF-β1 protein.