Objective To explore the safety of Yttrium-90 resin microsphere selective internal radiation therapy (⁹⁰Y-SIRT) on malignant liver tumors. Methods A retrospective analysis was conducted on 64 patients with malignant liver tumors who underwent ⁹⁰Y-SIRT from February 2023 to November 2024 at Weifang People’s Hospital. The clinical characteristics of the patients and the occurrence of adverse reactions after treatment were analyzed to assess the safety of ⁹⁰Y-SIRT. Results Among the 64 patients, there were 52 males (81.25%) and 12 females (18.75%); the average age was (56.29±11.08) years. Seven patients (10.94%) had tumors with maximum diameter of less than 5 cm, 38 patients (59.38%) had tumors with maximum diameter of 5-10 cm, and 19 patients (29.68%) had tumors with maximum diameter of greater than 10 cm. There were 47 cases (73.44%) of solitary lesions and 17 cases (26.56%) of multiple lesions; 53 cases (82.81%) were primary liver cancers and 11 cases (17.19%) were metastatic liver cancers. Of the 64 patients, 63 successfully completed the Technetium-99m macroaggregated albumin (^99mTc-MAA) perfusion test and received the ⁹⁰Y-SIRT; one patient received ⁹⁰Y-SIRT after the second ^99mTc-MAA perfusion test due to a work error. The most common adverse reactions included grade 1 alanine aminotransferase (ALT) elevation in 26 cases (40.62%) and grade 2 in 2 cases (9.37%), grade 1 aspartate aminotransferase (AST) elevation in 27 cases (42.18%) and grade 2 in 7 cases (10.93%); grade 1 nausea in 17 cases (26.56%) and grade 2 in 6 cases (9.37%); grade 1 abdominal pain in 12 cases (18.75%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%); grade 1 vomiting in 11 cases (17.18%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%). Conclusion The adverse reactions of ⁹⁰Y-SIRT for treating malignant liver tumors are mild, indicating good safety.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

The clinical data of 10 patients with pathologically confirmed primary hepatic neuroendocrine neoplasms (PHNENs) were retrospectively analyzed. The cohort included 8 males and 2 females, with a median age of 63 years. None presented with carcinoid syndrome. Three cases were detected incidentally during health check-ups, 2 presented with painless jaundice, and 5 reported abdominal distension or pain (1 with concurrent jaundice). Elevated tumor markers included carbohydrate antigen 19-9 in 4 cases, alpha-fetoprotein in 2 cases, and neuron-specific enolase in 1 case. All patients underwent surgical resection, including hepatectomy and hilar cholangiocarcinoma resection, combining with resection and reconstruction of right hepatic artery, resection of liver metastases and pancreaticoduodenectomy according to the extent of tumor invasion.Preoperative imaging failed to diagnose neuroendocrine neoplasms in all cases. Final pathological diagnoses were neuroendocrine tumor (NET) G2 in 5 cases, NET G3 in 1 case, and neuroendocrine carcinoma (NEC) in 4 cases. During the follow-up, 4 patients died and 6 survived. The study demonstrates that PHNENs lack specific clinical or imaging features, and the diagnosis relies on pathological examination after excluding metastatic disease. Radical resection remains the primary treatment, with prognosis varying significantly by tumor grade.
Humans ; Middle Aged ; Male ; Female ; Neuroendocrine Tumors/pathology* ; Liver Neoplasms/pathology* ; Retrospective Studies ; Aged ; Adult

Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future, aiming to provide valuable insights and references for the continued advancement of peptide-based drugs.
Humans ; Peptides/pharmacology* ; Animals ; Neoplasms/drug therapy* ; Drug Discovery ; Neurodegenerative Diseases/drug therapy* ; Diabetes Mellitus/drug therapy*

OBJECTIVE To compare the hepatotoxicity of raw Polygonum cuspidatum and its vinegar-processed， ginger- processed， and wine-processed products in mice. METHODS Acute toxicity was assessed using the maximum tolerated dose approach. Male Kunming mice were randomly assigned to blank group， raw drug group， vinegar-processed group， ginger-processed group and wine-processed group， with 16 mice in each group. Mice in the treatment groups received oral gavage of the corresponding preparation at a total dose of 192 g/kg （single gavage volume of 40 mL/kg， administered three times at 5-hour interval）. During the experiment， the mortality and general condition of mice in each group were observed. Eight mice from each group were sacrificed at 48 hours， and the remaining eight at 14 days after the last administration. Organ coefficients， serum biochemical indices and liver histopathology were compared among the groups. RESULTS No mortality was observed in any group throughout the study. At 4 hours after the last administration， mice in all treatment groups exhibited transient alterations in urine and feces， which resolved at 14 days after the last administration. No significant differences in body weight or average food intake were observed among groups at any time point （P＞0.05）. At 48 hours after the last administration， all treatment groups showed varying degrees of liver injury， most severe in the wine-processed group， followed by the raw drug group， and mildest in the vinegar- processed group. Compared with the blank group， liver coefficients were significantly elevated in the wine-processed group， while serum levels of alanine transaminase， aspartate transaminase， total bilirubin （TBil） and alkaline phosphatase （ALP） were significantly increased in the raw drug and wine-processed groups. Additionally， the serum levels of TBil and ALP were significantly elevated in the ginger-processed group （P＜0.05）. At 14 days after the last administration， liver histopathology and all quantitative indicators showed partial recovery. Serum levels of liver function parameters were markedly reduced compared with 48 hours after the last administration （P＜0.05）. CONCLUSIONS Both raw and processed P. cuspidatum exhibit hepatotoxicity， which is closely associated with the processing method， and the severity of hepatotoxicity follows the order： wine-processed product＞raw product＞ginger-processed product＞vinegar- processed product.

Objective:To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy.Methods:This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group, a 1∶2 match was performed using the propensity score matching method, and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fisher′s exact test were used to compare the data between the two groups,respectively. Results:After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant ( t=-3.800, P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml; U=1 026.500, P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28) in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups( P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the two groups( P=0.532, P=0.927). Conclusion:The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.

Objective:To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy.Methods:This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group, a 1∶2 match was performed using the propensity score matching method, and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fisher′s exact test were used to compare the data between the two groups,respectively. Results:After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant ( t=-3.800, P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml; U=1 026.500, P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28) in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups( P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the two groups( P=0.532, P=0.927). Conclusion:The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.

Background Per- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollu-tants. Industrial production and consumer use of PFAS are the primary sources of exposure in urban areas. E-waste recycling activities are also a significant source of environmental PFAS exposure. Objective To compare exposure profiles between traditional and emerging PFAS in neonatal cord blood collected from an e-waste recycling area and a general exposure area characterized by modern economic development (hereafter referred to as general exposure area). Methods Based on a birth cohort study conducted in 2018, 85 pregnant women were recruited (36 participants from an e-waste recycling area and 49 participants from a general exposure area). Neonatal cord blood was collected at delivery. Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to detect 28 common PFAS in the blood. A structured questionnaire was used to gather sociodemographic characteristics of the pregnant women. Mann-Whitney U tests were used to compare PFAS exposure levels in neonatal cord blood between the e-waste recycling area and the general exposure area. Multiple linear regression models were used to explore the influence of residing in the e-waste recycling area on neonatal PFAS exposure, with area as the independent variable and the natural logarithm of PFAS exposure levels as the dependent variable. Results A total of 22 PFAS were positive in neonatal cord blood, of which 13 congeners were 100% detectable in the samples from both areas. The median ∑PFAS exposure levels in neonatal cord blood were 14.19 ng·mL⁻¹ and 14.02 ng·mL⁻¹ for the e-waste recycling area and the general exposure area, respectively, with linear perfluorooctanoic acid (L-PFOA) showing the highest median concentration (5.49 ng·mL⁻¹ and 6.39 ng·mL⁻¹, respectively). The results of Mann-Whitney U tests showed that the median exposure levels of long-chain perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), and perfluorotridecanoic acid (PFTrDA), as well as emerging alternatives 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) and 8:2 chlorinated polyfluorinated ether sulfonate (8:2 Cl-PFESA), were higher in the e-waste recycling area than in the general exposure area. In contrast, the median exposure levels of short-chain perfluoropentanoic acid (PFPeA) and perfluorohexanoic acid (PFHxA), as well as perfluorooctanoic acid (PFOA) branched isomers, including perfluoro-6-methylheptanoic acid (iso-PFOA), perfluoro-5-methylheptanoic acid (5m-PFOA), and perfluoro-4-methylheptanoic acid (4m-PFOA), were lower in the e-waste recycling area than in the general exposure area (P<0.05). The multiple linear regression models showed that, compared to the general exposure area, neonatal cord blood in the e-waste recycling area had significantly higher exposure levels of long-chain PFDA, PFUnDA, PFDoDA, PFTrDA, and emerging alternatives 6:2 Cl-PFESA and 8:2 Cl-PFESA, with odds ratios of 1.95 (95%CI: 1.39-2.75), 2.10 (95%CI: 1.58-2.75), 2.12 (95%CI: 1.39-3.25), 2.64 (95%CI: 1.63-4.22), 3.46 (95%CI: 2.34-5.10), and 3.25 (95%CI: 2.01-5.26), respectively. Conversely, the exposure levels of short-chain PFPeA, PFHxA, and branched PFOA (br-PFOA) were significantly lower, with odds ratios of 0.44 (95%CI: 0.38-0.52), 0.30 (95%CI: 0.16-0.57), and 0.50 (95%CI: 0.38-0.67), respectively. Conclusion PFAS are widely present in neonatal cord blood in both the e-waste recycling area and the general exposure area. Compared to the general exposure area, the neonatal cord blood samples in the e-waste recycling area show higher exposure levels of certain long-chain perfluoroalkyl carboxylic acids (PFCA) and emerging PFAS alternatives, while the neonatal cord blood samples in the general exposure area show higher exposure levels of some short-chain PFCA and PFOA branched isomers.

Purpose To explore the clinical and pathologi-cal features and the relationships between pathological features and drugs of patients with drug-induced liver injury(DILI)based on the hepatotoxicity injury patterns.Methods The clin-ical data,laboratory indicators,drugs,and liver biopsy of 50 cases of DILI were collected,the expression of CK19 was detec-ted by immunohistochemistry EnVision two-step method,and the reticular scaffold of liver tissue was displayed by Reticular fiber staining.Results Among the 50 patients with DILI,there were 29 cases of hepatocellular DILI,11 cases of cholestatic DILI,and 10 cases of mixed DILI,respectively,with the hepatocellu-lar DILI accounting for the highest proportion(58％).7 catego-ries of drugs induced DILI,with herbal ranking first(52％).Different types of drugs could cause different types of DILI,with herbal induced 17 cases hepatocellular DILI(58.62％)and an-ti-infectious and anticancer drugs induced all 3 cases cholestatic DILI(27.27％).Different types of DILI displayed various pathological characteristics.Hepatocellular congestion,feathery degeneration,and small bile duct thrombosis primarily occur in cholestasis and mixed DILI,while bridging necrosis,sub-large and large necrosis were mainly seen in hepatocellular DILI.Conclusion Based on hepatotoxicity injury patterns,DILI ex-hibits a variety of clinical and pathological characteristics,and there is some relationship between pathological characteristics and drugs.Liver puncture pathological biopsy plays an important role in improving the diagnosis and treatment of DILI.

ObjectiveTo explore the efficacy and safety of Lianhua Qingwen preparation in the treatment of community-acquired pneumonia （CAP）. MethodThe PubMed，Embase，Cochrane Collaboration，CNKI，VIP，and Wanfang Medical Network database （CBM） were systematically searched for all the randomized controlled clinical trials （RCTS） of Lianhua Qingwen Preparation in the treatment of CAP from the establishment of the databases to February 2023. The inclusion criteria were established， and the search results were screened. The risk assessment tool （ROB） scale was used to evaluate the methodological quality of the final included studies， and the R software was used for data integration and meta-analysis. ResultA total of 30 pieces of literature were included，involving 2 800 patients. The combined use of Lianhua Qingwen preparation on the basis of antibiotics and other conventional treatments showed that Lianhua Qingwen preparation could improve the cure rate ［relative risk（RR）=1.32，95% confidence interval（95% CI）［1.23，1.42］，P<0.000 1）］ and shorten the time of fever remission ［Mean difference（MD）=-1.45，95% CI ［-1.93，-0.97］，P<0.000 1］，and the duration of fever reduction was divided into general population and special population subgroups. The results showed that Lianhua Qingwan preparation could shorten the duration of fever reduction （general population MD=-1.51，95%CI ［-2.07，-0.94］，P<0.000 1， special population MD=-1.22，95% CI ［-2.16，-0.29］，P=0.010 6）and does not increase the incidence of adverse reactions（RR=0.85，95%CI ［0.62，1.15］，P<0.000 1）. After nine pieces of virtual literature with negative results were supplemented by the shear compensation method，the cure rate of CAP by Lianhua Qingwan preparation was still improved （RR=1.20，95%CI ［1.13，1.29］，P<0.000 1）. ConclusionThe application of Lianhua Qingwen preparation on the basis of antibiotics in the treatment of CAP can improve the cure rate and shorten the time of fever reduction.