Immune checkpoint inhibitors (ICIs), as one of relatively advanced antitumor treatment methods in recent years, have achieved significant therapeutic effects in the treatment of multiple systemic tumors. However, their application in gastrointestinal tumors is not satisfactory, with treatment bottlenecks. This article summarizes the challenges and possible solutions faced by ICIs in the treatment of gastrointestinal tumors to help clinicians better understand the limitations and future development directions of ICIs and thus develop more effective treatment strategies.

Objective Hippocampal atrophy is a clinically important marker for the diagnosis of many psychiatric disorders such as Alzheimer’s disease‚ so accurate segmentation of the hippocampus is an important scientific issue. With the development of deep learning‚ a large number of advanced automatic segmentation method have been proposed. However‚ 3D hippocampal segmentation is still challenging due to the effects of various noises in MRI and unclear boundaries between various classes of the hippocampus. Therefore‚ the aim of this paper is to propose new method to segment the hippocampal head‚ body‚ and tail more accurately. Methods To overcome these challenges‚ this paper proposed two strategies. One was the spatial and frequency domain features adaptive fusion strategy‚ which reduced the influence of noise on feature extraction by automatically selecting the appropriate frequency combination through fast Fourier transform and convolution. The other was an inter-class boundary region enhancement strategy‚ which allowed the network to focus on learning the boundary regions by weighting the loss function of the boundary regions between each class to achieve the goal of pinpointing the boundaries and regulating the size of the hippocampal head‚ body and tail. Results Experiments performed on a 50-case teenager brain MRI dataset show that our method achieves state-of-the-art hippocampal segmentation. Hippocampal head‚ body and tail had been improved compared to the existing method. Ablation experiments demonstrated the effectiveness of our two proposed strategies‚ and we also validated that the network had a strong generalization ability on a 260-case Task04_Hippocampus dataset. It was shown that the method proposed in this paper could be used in more hippocampal segmentation scenarios. Conclusion The method proposed in this paper can help clinicians to observe hippocampal atrophy more clearly and accomplish more accurate diagnosis and follow-up of the condition.

With the development of modern medical standards,autoimmune diseases and their associ-ated successive osteoporosis have received increasing attention in recent years.Patients with autoimmune diseases,due to the characteristics of the disease and the prolonged use of glucocorticoid hormone thera-py,may affect the bone formation and bone absorption of the patient,followed by severe successive osteo-porosis,thereby increasing the risk of osteoporotic vertebral fractures.Vertebral compression fractures of the spine are common fracture types in patients with osteoporotic fractures.Osteoporosis is a common complication after glucocorticoid therapy in patients with autoimmune diseases.Percutaneous vertebro-plasty(PVP)and percutaneous kyphoplasty(PKP)are minimally invasive operation and are commonly used surgical methods for the treatment of osteoporotic vertebral compression fractures.However,due to the operation of spinal puncture during the operation,there are serious surgical risks such as bone cement leakage,spinal epidural hemorrhage,subdural hemorrhage,and subarachnoid hemorrhage in both PVP and PKP.As a result,it is necessary to evaluate the patient's body before surgery carefully,especially in the case of blood coagulation.This article reports a case of autoimmune disease patient admitted to Peking University People's Hospital due to lumbar 4 vertebral compression fracture combined with Sj?gren's syn-drome.The patient's preoperative examination showed that the activated partial thromboplastin time(APTT)was significantly prolonged.After completing the APTT extended screening experiment and lu-pus anticoagulant factor testing,the multi-disciplinary team(MDT)of Peking University People's Hospi-tal jointly discussed the conclusion that the patient's test results were caused by an abnormal self-immuni-ty anti-copulant lupus(LAC).Based on the results of the laboratory examination,the patient was con-sidered to be diagnosed with combined antiphospholipid syndrome(APS).For such patients,compared with the patient's tendency to bleed,we should pay more attention to the risk of high blood clotting in the lower limbs of the patient,pulmonary clots and so on.With timely anti-coagulation treatment,the patient safely passed the peripheral period and was successfully discharged from the hospital.Therefore,for pa-tients with autoimmune diseases with prolonged APTT in the perioperative period,doctors need to careful-ly identify the actual cause and carry out targeted treatment in order to minimize the risk of surgical and perioperative complications and bring satisfactory treatment results to the patients.

OBJECTIVE: To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN). METHODS: A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014. RESULTS: A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer. CONCLUSIONS No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.
Humans ; Retrospective Studies ; Incidence ; Carcinoma, Hepatocellular ; Liver Neoplasms/epidemiology* ; Kidney Diseases/chemically induced* ; Aristolochic Acids/adverse effects*

Pentacyclic triterpenoids are a class of widespread natural compounds containing six isoprene structures with a wide range of pharmacological activities, including antibacterial, anti-inflammatory, antiviral, antitumor, immune regulation, etc. The structural modifications of pentacyclic triterpenoid natural products and the drug development have always been a hot research topic. This article reviews the recent progresses in the structural modifications, pharmacological effects, and clinical studies of different kinds of pentacyclic triterpenoid natural products.

Objective To evaluate the bioequivalence of test product and reference product in a single dose of amoxicillin clavulanate potassium tablet under fasting and fed conditions in healthy volunteers.Methods An open label,randomized,single dose,four-period,crossover bioequivalence study was designed.Fasting and postprandial tests were randomly divided into 2 administration sequence groups according to 1:1 ratio,amoxicillin clavulanate potassium tablet test product or reference product 375 mg,oral administration separately,liquid chromatography tanden mass spectrometry was applied to determine the concentration of amoxicillin and clavulanate potassium in plasma of healthy subjects after fasting or fed administration,while Phoenix WinNonlin 8.2 software were used for pharmacokinetics(PK)parameters calculation and bioequivalence analysis.Results Healthy subjects took the test product and the reference product under fasting condition,the main PK parameters of amoxicillin are as follows:Cmax were(5 075.57±1 483.37)and(5 119.86±1 466.73)ng·mL-1,AUC0_twere(1.32 × 104±2 163.76)and(1.30 × 104±1 925.11)ng·mL-1,AUC0-∞were(1.32 × 104±2 175.40)and(1.31 ×104±1 935.86)ng·mL-1;the main PK parameters of clavulanic acid are as follows:Cmax were(3 298.27±1 315.23)and(3 264.06±1 492.82)ng·mL-1,AUC0-twere(7 690.06±3 053.40)and(7 538.39±3 155.89)ng·mL-1,AUC0-∞were(7 834.81±3 082.61)and(7 671.67±3 189.31)ng·mL-1;the 90％confidence intervals of Cmax,AUC0-tand AUC0-∞ after logarithmic conversion of amoxicillin and clavulanate potassium of the two products were all within 80.00％-125.00％.Healthy subjects took the test and reference product under fed condition,the main PK parameters of amoxicillin are as follows:Cmax were(4 514.08±1 324.18)and(4 602.82±1 366.48)ng·mL-1,AUC0-twere(1.15 × 104±1 637.95)and(1.15 × 104±1 665.69)ng·mL-1,AUC0-∞ were(1.16 × 104±1 646.26)and(1.15 × 104±1 607.20)ng·mL-1;the main PK parameters of clavulanic acid are as follows:Cmax were(2 654.75±1 358.29)and(2 850.51±1 526.31)ng·mL-1,AUC0-twere(5 882.82±2 930.06)and(6 161.28±3 263.20)ng·mL-1,AUC0-∞ were(6 022.70±2 965.05)and(6 298.31±3 287.63)ng·mL-1;the 90％confidence intervals of Cmax,AUC0-t and AUC0-∞ after logarithmic conversion of amoxicillin and clavulanate potassium of the two products were all within 80.00％-125.00％.Conclusion The two formulations were bioequivalent to healthy adult volunteers under fasting and fed conditions.

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.

RNA fluorescence aptamers are RNA sequences that can specifically bind to non-toxic,cell permeable,and self-fluorescent target molecules and activate their luminescent properties.These aptamers provide powerful tools for biosensing and imaging researches due to their simple structure,easy synthesis,and easy transfection.This article summarized the characteristics and development history of various RNA fluorescent aptamers,including Malachite Green,Spinach,Broccoli,Mango,Corn,and Pepper family,as well as their corresponding fluorescent groups.The applications of RNA fluorescent aptamers were also reviewed from two aspects:extracellular detection and cell imaging.This review might provide guidance for labeling,detection and interactions of molecules from proof of concept and clinical assessment to practical clinical and biomedical applications.

Objective Previous studies on the association between lipid profiles and chronic kidney disease(CKD)have yielded inconsistent results and no defined thresholds for blood lipids. Methods A prospective cohort study including 32,351 subjects who completed baseline and follow-up surveys over 5 years was conducted.Restricted cubic splines and Cox models were used to examine the association between the lipid profiles and CKD.A regression discontinuity design was used to determine the cutoff value of lipid profiles that was significantly associated with increased the risk of CKD. Results Over a median follow-up time of 2.2(0.5,4.2)years,648(2.00%)subjects developed CKD.The lipid profiles that were significantly and linearly related to CKD included total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),TC/HDL-C,and TG/HDL-C,whereas low-density lipoprotein cholesterol(LDL-C)and LDL-C/HDL-C were nonlinearly correlated with CKD.TC,TG,TC/HDL-C,and TG/HDL-C showed an upward jump at the cutoff value,increasing the risk of CKD by 0.90%,1.50%,2.30%,and 1.60%,respectively,whereas HDL-C showed a downward jump at the cutoff value,reducing this risk by 1.0%.Female and participants with dyslipidemia had a higher risk of CKD,while the cutoff values for the different characteristics of the population were different. Conclusion There was a significant association between lipid profiles and CKD in a prospective cohort from Northwest China,while TG,TC/HDL-C,and TG/HDL-C showed a stronger risk association.The specific cutoff values of lipid profiles may provide a clinical reference for screening or diagnosing CKD risk.

Purpose::To explore the effect of green channel for stroke patients on the treatment of severe aneurysmal subarachnoid hemorrhage.Methods::This is a retrospective case-control study. The clinical data of patients with severe aneurysmal subarachnoid hemorrhage admitted to the emergency department of our hospital from January 2015 to June 2022 were retrospectively analyzed. Patients diagnosed with subarachnoid hemorrhage, confirmed intracranial aneurysm by preoperative CT angiography or digital subtraction, graded Hunt-Hess grade III, IV, and V, < 72 h from the onset to the time of consultation received surgical treatment in our hospital were included in this study. Patients with serious underlying diseases, such as heart, liver, kidney diseases, or malignant tumors, traumatic subarachnoid hemorrhage, previous history of cerebral hemorrhage, and incomplete data were excluded. The control group included patients with severe aneurysmal subarachnoid hemorrhage admitted from January 2015 to December 2018 before the establishment of the green channel for stroke patients, and the observation group included patients with severe aneurysmal subarachnoid hemorrhage admitted from January 2019 to June 2022 after the establishment of the green channel. The control group received routine treatment in the emergency department; the observation group received improved treatment of green channel for stroke patients. Gender, age, Hunt-Hess grade on admission, modified Rankin scale (mRS) on admission, aneurysm location, aneurysm size and whether accompanied by intracerebral hemorrhage, the time from onset to emergency department, the time from emergency department to vascular diagnostic examination, the time from onset to surgery, the time from emergency department to surgery, the time from hospital admission to surgery, length of hospital stay, complications, treatment effect were analyzed and compared between the 2 groups. SPSS 23.0 software was utilized to conduct comparisons between the 2 groups. The t-test, Chi-square test, or Mann-Whitney U test was chosen based on the data type. Statistical significance was established when p < 0.05. Results::A total of 71 patients were included in this study, of whom 37 were in the control group and 34 were in the observation group. There were no statistical differences in age, gender, Hunt-Hess grade, mRS scores, aneurysm location, aneurysm size, intracerebral hemorrhage, the time from onset to emergency department, length of hospital stay, complications between the observation group and the control group (all p > 0.05). The time (min) from visit to vascular diagnostic test (60.50 vs. 120.00, p =0.027), the time (min) from onset to surgery (1792.00 vs. 2868.00, p =0.023), the time (min) from emergency department to surgery (1568.50 vs. 2778.00, p =0.016), the time (min) from hospital admission to surgery (1188.50 vs. 2708.00, p =0.043), all of them were shorter in the observation group than those in the control group. The relative values of admission and 7-day postoperative mRS scores and the relative values of admission and discharge mRS scores ≥ 2 were used as the criteria for determining better efficacy, and the treatment effect was better than that in the control group, and the differences were statistically significant (admission to 7 days postoperative mRS score ≥ 2, 17 (50.0 %) vs. 8 (21.6 %), p =0.012; admission to discharge mRS score ≥ 2, 19 (55.9 %) vs. 11 (29.7 %), p =0.026). Conclusion::The green channel for stroke patients with severe aneurysmal subarachnoid hemorrhage can effectively shorten the time from arrival at the emergency department to vascular diagnostic examination and the time from the emergency department to surgery, and achieve a better therapeutic effect, which is worth popularizing and applying.