Objective:To evaluate the efficacy and safety of lenvatinib combined with camrelizumab as the second-line treatment for advanced intrahepatic cholangiocarcinoma (ICC).Methods:The clinical data of patients with advanced ICC undergoing the second-line treatment of lenvatinib combined with camrelizumab in the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University from June 2021 to June 2022 were screened and analyzed. A total of 12 patients were enrolled, including seven males and five females, aged (67.5±8.6) years. Response evaluation criteria in solid tumor 1.1 was used to evaluate the efficacy of treatment. The safety assessment adopts the Adverse Event Evaluation Standard 5.0. Kaplan-Meier method was conducted to plot survival curves.Results:Among the 12 patients (after 1-7 cycles of immune and targeted therapy), three achieved partial response, four achieved stable disease, and five were defined as progression disease. Adverse events of different degrees occurred in seven cases, among which three patients had adverse events of grade ≥ 3: one with hypertension, which was managed after antihypertensive and symptomatic treatment; one with elevated serum total bilirubin, which was improved after reducing the dose of lenvatinib; one with liver dysfunction, which was considered as immune-related liver toxicity and alleviated after discontinuing camrelizumab. The 1-month, 3-month, and 6-month survival rates and progression-free survival rates of the patients were 100.0%, 91.7%, 66.7%, and 83.3%, 41.7%, and 25.0%, respectively. The median overall survival of patients was 14.7 months (95% CI: 9.2-21.2) and the median time to progression was 8.0 months (95% CI: 4.1-11.9). Conclusion:Combination of lenvatinib and camrelizumab could bring survival benefits with controllable adverse events as the second-line treatment of patients with advanced ICC.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Additive manufacturing(3D printing)technology aligns with the direction of precision and customization in future medicine,presenting a significant opportunity for innovative development in high-end medical devices.Currently,research and industrialization of 3D printed medical devices mainly focus on nondegradable implants and degradable implants.Primary areas including metallic orthopaedic implants,polyether-ether-ketone(PEEK)bone implants,and biodegradable implants have been developed for clinical and industrial application.Recent research achievements in these areas are reviewed,with a discussion on the additive manufacturing technologies and applications for customized implants.Challenges faced by different types of implants are analyzed from technological,application,and regulatory perspectives.Furthermore,prospects and suggestions for future development are outlined.

The incidence rate of inflammatory bowel disease(IBD)in China is in a rapid rise period in recent years,and the course of the disease is repeated and prolonged.The risk of IBD combined with thromboembolism is significantly increased,and it is one of the important reasons for poor prognosis in IBD patients.However,the pathological and physiological mechanisms of thromboembolism have not been fully understood and have not received sufficient attention from clinical physicians.This article aims to provide a systematic review of the risks and mechanisms of thromboembolism in IBD,and to summarize the progress in its prevention and treatment strategies,in order to be helpful for the prevention and treatment of thromboembolism in IBD patients.

Objective:To investigate the value of CD64 index and C-reactive protein (CRP)/albumin (Alb) ratio (CRP/Alb) in predicting infection after modified radical mastectomy for breast cancer.Methods:The clinical data of 203 breast cancer patients who underwent modified radical mastectomy from January 2018 to August 2021 in Anhui No.2 Provincial People's Hospital were retrospectively analyzed. All cases were divided into infection group (40 cases) and non-infection group (163 cases) according to whether they were infected at the 1st month after operation. On the 1st day after operation, the serum CD64 index was measured by using flow cytometry, the serum CRP and Alb levels were measured by using immunoturbidimetry, and the CRP/Alb was calculated. The values of CD64 index and CRP/Alb in the diagnosis of infection after modified radical mastectomy for breast cancer were evaluated by using receiver operating characteristic (ROC) curve. The factors influencing infection after modified radical mastectomy for breast cancer were explored by using multivariate logistic regression.Results:The levels of CD64 index, CRP, CRP/Alb in the infection group were higher than those in the non-infection group [5.7±1.1 vs. 1.5±0.3, t = 32.05, P < 0.001; (78±13) mg/L vs. (11±3) mg/L, t = 39.26, P <0.001; 3.09±0.42 vs. 0.36±0.02, t = 57.48, P < 0.001], and the level of Alb in the infection group was lower than that in the non-infection group [(25±3) g/L vs. (32±4) g/L, t = 8.37, P < 0.001]. There were statistically significant differences in the catheterization time, CD64 index and CRP/Alb between the infection group and non-infection group (all P < 0.05); multivariate logistic regression showed that catheterization time >9 d, CD64 index >42.65 and CRP/Alb >1.25 were risk influencing factors of infection after modified radical mastectomy for breast cancer (all P < 0.001). The ROC curve results showed that the area under the curve, sensitivity, and specificity of CD64 index in the diagnosis of infection after modified radical mastectomy for breast cancer were 0.804, 89.5% and 85.4%, the CRP were 0.712, 70.6% and 76.5%, the Alb were 0.766, 72.4% and 75.4%, and the CRP/Alb ratio were 0.856, 88.0% and 90.5%. Conclusions:The CD64 index and CRP/Alb have certain values in the prediction of infection after modified radical mastectomy for breast cancer.

Background: Acute non-variceal upper gastrointestinal bleeding (ANVUGIB) is one of the most common acute and severe clinical entities. As the limited medical resource in remote regions or primary hospitals, it is necessary to explore an effective endoscopic hemostasis method in such a medical condition. Aims: To investigate the efficacy of norepinephrine injection combined with electrocoagulation under conventional endoscopy in patients with ANVUGIB. Methods: Clinical data of 123 ANVUGIB patients were collected retrospectively from January 2019 to December 2021 at the Kashgar Prefecture Second People’s Hospital. According to the endoscopic hemostasis method used initially, these patients were divided into group A (submucosal injection of norepinephrine), group B (electrocoagulation), group C (clip hemostasis) and group D (direct norepinephrine injection combined with electrocoagulation). The success rate of immediate hemostasis, operation time, rebleeding rate within 72 hours, and rate of transfer to surgery were compared between the four groups. Furthermore, the relationship between visual field during hemostasis and success of immediate hemostasis was analyzed. Results: In group D, all patients achieved success immediate hemostasis, the success rate (100%) was significantly higher than that in group A, group B, and group C (all P<0.05). No rebleeding and surgical transfer was observed in group D. The operation time of group D was (17.84±6.78) min, which was not significantly different from that of group A and group C (all P>0.05). In patients treated with combined hemostasis, including initial combination strategy and failed cases transferred to combination strategy, a clear endoscopic visual field could be obtained in 94.2% of the cases, and the success rate of immediate hemostasis was 98.1%. Conclusions: Submucosal injection of norepinephrine combined with electrocoagulation under conventional endoscopy has a higher immediate hemostasis rate with lower rates of rebleeding and surgical transfer in ANVUGIB patients. This strategy is worthy for popularizing in remote regions and primary hospitals.

Objective:To analyze the correlation of serum lipoprotein-associated phospholipase A2(Lp-PLA2)and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)levels with the severity of coronary heart disease in elderly patients.Methods:Clinical data of 200 elderly patients with coronary heart disease in the hospital from January 2017 to July 2019 were retrospectively collected.Data of 80 healthy elderly patients undergoing regular physical examinations in our hospital during the same period were collected and used as the healthy control group.All patients received laboratory tests using relevant parameters and coronary angiography on admission, with complete records of examination results for analysis.Based on SYNTAX scores from angiography of coronary artery lesions, all 200 elderly patients with coronary heart disease were further divided into a low-risk lesion subgroup, an intermediate-risk lesion subgroup and a high-risk lesion subgroup.The correlation of serum Lp-PLA2 and NLRP3 levels with the severity of coronary lesions was analyzed in elderly patients with coronary heart disease.Results:The mean SYNTAX score was 27.6±10.1.There were 60 cases with low-risk lesions, 68 cases with intermediate-risk lesions and 72 cases with high-risk lesions, accounting for 30.0%, 34.0% and 36.0%, respectively.The control group had the lowest serum levels of Lp-PLA2 and NLRP3, followed by the low-risk lesion, intermediate-risk lesion and high-risk lesion subgroups( F=305.026, 9.173 and 582.029, all P<0.001). Bivariate Pearson correlation analysis showed that serum levels of Lp-PLA2 and NLRP3 were positively correlated to the Syntax score in elderly patients with coronary heart disease( r=0.545 and 0.689, all P<0.001). Conclusions:Serum levels of Lp-PLA2 and NLRP3 are correlated to the severity of coronary artery disease in elderly patients with coronary heart disease.Overexpression of these two markers may indicate growing severity of coronary artery disease.Testing for serum Lp-PLA2 and NLRP3 levels in elderly patients with coronary heart disease can be considered to evaluate coronary lesions and treatment options in the future.

Objective:To examine potential predisposing risk factors for coronary heart disease(CHD)in elderly patients and the correlation between serum uric acid levels and the predisposing risk factors in elderly patients with CHD.Methods:Clinical data of 200 elderly inpatients with CHD(CHD group)and 150 elderly outpatients without CHD(control group)at our hospital from January 2017 to January 2019 were retrospectively analyzed.Peripheral venous blood was collected from patients immediately after admission, and serum uric acid levels were measured.Baseline information of patients was recorded.Potential predisposing risk factors of CHD were identified by single-factor and multiple-factor analysis, and serum uric acid levels were compared against predisposing risk factors.The correlation between serum uric acid levels and predisposing risk factors in elderly patients with CHD was analyzed.Results:According to preliminary single-factor analysis, smoking, diabetes mellitus, low high-density lipoprotein cholesterol(HDL-C)hypolipidemia, family history of CHD and glomerular filtration rate seemed to be predisposing risk factors for elderly patients with CHD( χ2=6.739, 15.655, 6.331, 9.615, 23.279, P<0.05). Multiple-factor analysis showed that smoking, diabetes mellitus, low HDL-C hypolipidemia, family history of CHD and glomerular filtration rate were predisposing risk factors for elderly patients with CHD( OR=1.777, 2.381, 1.883, 1.967, 3.205, all P<0.05). Serum uric acid levels in elderly CHD patients with smoking, diabetes mellitus, low HDL-C hypolipidemia, family history of CHD or glomerular filtration rate<100 ml/min were higher than in patients without any of those conditions, and the difference was statistically significant( t=8.017, 5.907, 8.509, 7.164, 13.839, P<0.001). Spearman correlation analysis showed that serum uric acid levels were positively correlated with risk factors such as smoking, diabetes mellitus, and family history of CHD in elderly patients with CHD( r=0.409, 0.422, 0.422, all P<0.001), and were negatively correlated with low HDL-C hypolipidemia and glomerular filtration rate( r=-0.428 and -0.481, all P<0.001). Conclusions:High level serum uric acid is closely related to many CHD risk factors such as smoking and diabetes mellitus and may be an independent risk factor for the onset of CHD.

Immunoproteasome is associated with various diseases such as hematologic malignancies, inflammatory, autoimmune and central nervous system diseases, and over expression of immunoproteasome is observed in all of these diseases. Immunoproteasome inhibitors can reduce the expression of immunoproteasome by inhibiting the production of related cell-inducing factors and the activity of T lymphocyte for treating related diseases. In order to achieve good efficacy and reduce the toxic effects, key for development of selective immunoproteasome inhibitors is the high selectivity and potent activity of the three active subunits of the proteasome. This review summarizes the structure and functions of immunoproteasome and the associated diseases. Besides, structure, activity and status of selective immunoproteasome inhibitors are also been highlighted.

Objective To study the mechanism of RING finger protein 34 ( RNF34 ) involved in innate immunity . Methods Recombinant PCR was used and transient expression of the plasmid was achieved in HEK 293T cells.The cells were stimulated with Sendai virus ( SeV) or N-RIG-Ⅰfor the indicated time while luciferase activity was observed using the dual-luciferase reporter assay kit .Results We constructed the plasmid pcDNA 3-Flag-RNF34 and its three mutations .The study found that when stimulated by SeV , RNF34 could inhibit the activity of NF-κB and IFN-βmore significantly than RNF34-ΔFYVE, RNF34-ΔCID and RNF34-ΔRING.We also found that RNF 34 and its three mutants had similar inhibitory effect when the activation of NF-κB and IFN-βwas stimulated by the N-RIG-Ⅰ.Conclusion RNF34 negatively regulates innate immunity by acting on the RIG-Ⅰ-MAVS signaling pathway .