This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Crigler-Najjar syndrome (CNS) and Gilbert syndrome (GS; OMIM: 143500) are rare autosomal recessive diseases that cause unconjugated hyperbilirubinemia due to decreased UGT1A1 enzyme activity. Crigler-Najjar syndrome type 2 (CNS2; OMIM: 606785) increases the risk of gallbladder stone formation and cholecystitis, while GS seldom causes health issues. We found a 28-year-old male patient with recurring right upper abdomen pain who experienced persistent jaundice from birth. CNS2 with gallbladder stones and cholecystitis was diagnosed after genetic testing revealed rare double homozygous mutations A(TA)₇TAA (rs3064744) and P229Q (rs35350960) in the UGT1A1 gene. After pedigree investigation, we found that the patient's parents with modestly increased bilirubin had compound heterozygous mutations A(TA)₇TAA and P229Q, which were GS. Bioinformatics analysis showed that A(TA)₇TAA is in the TATA-box region of the gene UGT1A1 promoter, affecting gene transcriptional initiation, whereas P229Q modifies protein three-dimensional structure and may be harmful. In this pedigree, double homozygous mutations have a more severe phenotype than compound heterozygous mutations. Inherited causes of hyperbilirubinemia should be suspected after ruling out biliary obstruction, and early bilirubin reduction (< 103 µmol/L (6 mg/dL)) may reduce the risk of complications like cholecystitis in CNS2 patients, though further studies with longer follow-up are needed to confirm this observation.
Humans ; Male ; Glucuronosyltransferase/genetics* ; Adult ; Crigler-Najjar Syndrome/complications* ; Cholecystitis/etiology* ; Homozygote ; Mutation ; Pedigree

ObjectiveTo realize the automatic recognition of the slicing angles of Fritillariae Thunbergii Bulbus （FTB） based on the improved YOLOv7-tiny algorithm. MethodFirstly， a diverse dataset of FTB images， totaling 16 000 pictures， with various angles was constructed. Furthermore， improvements were made to YOLOv7-tiny by replacing standard convolutions with ghost convolution （GhostConv）， incorporating the coordinate attention （CA） mechanism as a preferred addition， substituting some activation functions with HardSwish function for decreasing the floating point operations. Additionally， a penalty term for angle recognition error was integrated into the loss function， and modifications were made to the non-maximum suppression （NMS） strategy to address cases where multiple detection results were associated with the same target. In order to verify the effectiveness of different improvement points on the optimization of the algorithm model， ablation experiments were carried out on all the improvement points， and the effectiveness of the improvement points was proved by comparing the prediction results before and after the addition of a certain improvement point on the basis of the original model or the model with the addition of an improvement point that has been verified to be effective， in order to evaluate the improvement of the indexes. ResultThe number of parameters required for the improved slicing angle recognition algorithm of FTB was about 55.4% of the original algorithm， and the amount of computation was about 59.4% of the original algorithm. The mAP@0.5［mean average precision at an intersection over union（IoU） of 0.5］ increased by 12.2%， the mean absolute error（MAE） of the recognized angle was 5.02°， representing a reduction of 4.58° compared to the original algorithm. In the experimental environment of this paper， the average recognition time per image was as low as 8.7 ms， significantly faster than the average human reaction time. ConclusionThis study， by utilizing the improved YOLOv7-tiny algorithm， achieves effective slicing angle recognition of FTB with high accuracy and more lightweight， which provides a novel approach for stable and precise automated slicing of FTB， thereby providing valuable insights into the automation of processing other traditional Chinese medicines.

The paper summarizes the imaging evaluation methods for assessing the degree of carotid artery stenosis and analyzes the unique advantages and limitations of various imaging techniques in vascular imaging based on existing guidelines and consensus.The paper focuses on reviewing the clinical applications of several novel ultrasound technologies,including the use of advanced hemodynamic parameters such as blood flow dispersion(Tur index)and wall shear stress(WSS).Carotid artery stenosis is closely associated with cardiovascular disease.Although non-invasive and radiation-free ultrasound technology has certain limitations in diagnostic accuracy to a certain extent,with the continuous emergence of advanced functions such as ultrasound hemodynamics and vascular elasticity,the combination of multi-modality and multi-parameter ultrasound is expected to become an important method for efficient diagnosis of arterial stenosis in the future.

Objective:This study aims to explore the temporal trend of Low Anterior Resection Syndrome (LARS) and its symptoms after laparoscopic anterior resection for rectal cancer.Methods:A retrospective cohort study design was employed. The study included primary rectal (adenocarcinoma) cancer patients who underwent laparoscopic anterior resection at Tongji Hospital, Huazhong University of Science and Technology, between January 1, 2010, and December 31, 2020. Complete medical records and follow-up data at 3, 6, 9, 12, and 18 months postoperatively were available for all patients. A total of 1454 patients were included, of whom 1094 (75.2%) were aged ≤65 years, and 597 (41.1%) were females. Among them, 1040 cases (71.5%) had an anastomosis-to-anus distance of 0-5cm, and 86 cases (5.9%) received neoadjuvant treatment. All patients completed the Chinese version of the LARS questionnaire and their LARS occurrence and specific symptom information were recorded at 3, 6, 9, 12, and 18 months postoperatively. Considering past literature and clinical experience, further subgroup analyses were performed to explore the potential impact factors on severe LARS, including anastomosis level, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and the presence of preventive stoma.Results:The occurrence rates of LARS at 3, 6, 9, 12, and 18 months postoperatively were 78.5% (1142/1454), 71.4% (1038/1454), 55.0% (799/1454), 45.7% (664/1454), and 45.7% (664/1454), respectively (χ 2=546.180 , P<0.001). No statistically significant difference was observed between the 12-month and 18-month time points ( P>0.05). When compared with the symptoms at 3 months, the occurrence rates of gas incontinence [1.7% (24/1454) vs. 33.9% (493/1454)], liquid stool incontinence [3.9% (56/1454) vs. 41.9% (609/1454)], increased stool frequency [79.6% (1158/1454) vs. 95.9% (1395/1454)], stool clustering [74.3% (1081/1454) vs. 92.9% (1351/1454)], and stool urgency [46.5% (676/1454) vs. 78.7% (1144/1454)] in the LARS symptom spectrum were significantly alleviated at 12 months (all P<0.05) and remained stable beyond 12 months (all P>0.05). With the extension of postoperative time, the incidence rates of severe LARS exhibited a decreasing trend in different subgroups, of anastomosis level, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and the presence of preventive stoma, and reached stability at 12 months postoperatively (all P>0.05). Conclusion:LARS and its specific symptom profile showed a trend of gradual improvement over time up to 1 year postoperatively, and stabilized after more than 1 year. Increased stool frequency and stool clustering are the most common features of abnormal bowel dys function, which improve slowly after surgery.

Objective:This study aims to explore the temporal trend of Low Anterior Resection Syndrome (LARS) and its symptoms after laparoscopic anterior resection for rectal cancer.Methods:A retrospective cohort study design was employed. The study included primary rectal (adenocarcinoma) cancer patients who underwent laparoscopic anterior resection at Tongji Hospital, Huazhong University of Science and Technology, between January 1, 2010, and December 31, 2020. Complete medical records and follow-up data at 3, 6, 9, 12, and 18 months postoperatively were available for all patients. A total of 1454 patients were included, of whom 1094 (75.2%) were aged ≤65 years, and 597 (41.1%) were females. Among them, 1040 cases (71.5%) had an anastomosis-to-anus distance of 0-5cm, and 86 cases (5.9%) received neoadjuvant treatment. All patients completed the Chinese version of the LARS questionnaire and their LARS occurrence and specific symptom information were recorded at 3, 6, 9, 12, and 18 months postoperatively. Considering past literature and clinical experience, further subgroup analyses were performed to explore the potential impact factors on severe LARS, including anastomosis level, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and the presence of preventive stoma.Results:The occurrence rates of LARS at 3, 6, 9, 12, and 18 months postoperatively were 78.5% (1142/1454), 71.4% (1038/1454), 55.0% (799/1454), 45.7% (664/1454), and 45.7% (664/1454), respectively (χ 2=546.180 , P<0.001). No statistically significant difference was observed between the 12-month and 18-month time points ( P>0.05). When compared with the symptoms at 3 months, the occurrence rates of gas incontinence [1.7% (24/1454) vs. 33.9% (493/1454)], liquid stool incontinence [3.9% (56/1454) vs. 41.9% (609/1454)], increased stool frequency [79.6% (1158/1454) vs. 95.9% (1395/1454)], stool clustering [74.3% (1081/1454) vs. 92.9% (1351/1454)], and stool urgency [46.5% (676/1454) vs. 78.7% (1144/1454)] in the LARS symptom spectrum were significantly alleviated at 12 months (all P<0.05) and remained stable beyond 12 months (all P>0.05). With the extension of postoperative time, the incidence rates of severe LARS exhibited a decreasing trend in different subgroups, of anastomosis level, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and the presence of preventive stoma, and reached stability at 12 months postoperatively (all P>0.05). Conclusion:LARS and its specific symptom profile showed a trend of gradual improvement over time up to 1 year postoperatively, and stabilized after more than 1 year. Increased stool frequency and stool clustering are the most common features of abnormal bowel dys function, which improve slowly after surgery.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Objective: To evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.
Humans ; Middle Aged ; Aged ; Multiple Myeloma/drug therapy* ; Bendamustine Hydrochloride/therapeutic use* ; Prospective Studies ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective:Evaluation of ultrasound-guided radiofrequency of hyperthermia combined with recombinant human adenovirus H101 for the treatment of hepatocellular carcinoma (HCC).Methods:In vitro cell therapy experiments, luciferase/red fluorescent protein/lentivirus mediated McA-RH7777 cells were conducted and divided into 4 groups. Each group was repeatedly treated for 6 times: (1) recombinant human adenovirus type 5 H101 [(multiplicity of infection, MOI)=0.2]+ RFH group, heated at 42℃ for 30 min; (2) recombinant human adenovirus type 5 H101 alone (MOI=0.2); (3) RFH alone, heated at 42℃ for 30 min; (4) control group: physiological saline group. Twenty-four nude rats weighing 180-220 g were selected to establish a nude rat model of orthotopic HCC. They were divided into 4 groups with 6 rats in each group: (1) H101+ RFH combined treatment group: RFH electrode needles were punctured to the center of the tumor in the liver of nude rats under ultrasound guidance, and H101 was directly injected through the electrode injection end. RFH was delivered to the tumor at a temperature of 42℃ for 30 min; (2) H101 treatment group: MOI=0.2; (3) RFH treatment group; (4) sham surgery group. Fluorescence microscopy imaging was used to evaluate the viability of cells in vitro experiments. For in vivo validation, ultrasound imaging was used to follow up the tumor size. Tumor gross specimens and pathological changes were also evaluated.Results:Twenty-four hours after treatment, the survival rate of cells in the H101+ RFH group was the lowest under fluorescence microscopy. The results of MTS quantitative analysis showed that the relative absorbance of mezzanine in the H101+ RFH group cells was lower than that in the H101 group alone [(25.00±2.27)% vs. (69.50±4.53)%], the RFH group alone [(25.00±2.27)% vs. (92.83±1.66)%], and the control group [(25.00±2.27)% vs. 100%], with statistical significance (all P<0.001). The number of apoptotic cells in the H101+ RFH group was higher than that in the H101 group alone [(54.5±3.1)% vs. (25.2±1.4)%], the RFH group alone [(54.5±3.1)% vs. (5.7±0.6)%], and the control group [(54.5±3.1)% vs. (3.9±0.5)%], all of which showed statistically significant differences (all P<0.001). The relative tumor volume of nude rats in the H101+ RFH combination treatment group was smaller than that in the H101 treatment group (0.776±0.127 vs. 1.312±0.188), RFH treatment group (0.776±0.127 vs. 1.893±0.571), and sham surgery group (0.776±0.127 vs. 1.977±0.590), all of which had statistical significance (all P<0.001). The number of apoptotic cells in nude rats in the H101+ RFH combination treatment group was higher than that in the H101 treatment group [(49.85±4.00%)% vs. (22.70±0.65)%], the RFH treatment group [(49.85±4.00% vs. (5.36±0.84)%], and the sham surgery group [(49.85±4.00)% vs. (5.96±0.78)%], all of which showed statistically significant differences (all P<0.001). Conclusion:Ultrasound guided RFH combined with recombinant human adenovirus H101 has a promoting effect on the treatment of HCC.