Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Xanthine oxidase (XO) is an important therapeutic target for the treatment of hyperuricemia and gout. Based on the previously identified potent XO inhibitor 1, seventeen oxadiazoles and their ring-opening analogues were designed and synthesized via the bioisostere replacement strategy. Among them, compounds 2l, 2n, and 3b showed obvious XO inhibitory activity at the concentration of 10 μmol·L^-1, and compound 3b exhibited an IC₅₀ value of 1.45 μmol·L^-1.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Objective:To evaluate the clinical outcomesof primary reverse total shoulder arthroplasty (RTSA) and revision procedure with RTSA after treatment failure of complex proximal humeral fractures in the elderly.Methods:A retrospective analysis was conductedon 24 elderly patients with Neer three- or four-part proximal humeral fractures who underwent RTSA revision after treatment failure (RTSA revision group) from January 2017 to June 2022. There were 7 males and 17 females included, with a mean age of 78.23±5.78 years (range, 67-86 years). Forty-eight patients who underwent primary RTSA (primary RTSA group) during the same time period were selected by propensity score matchingin a 1∶2 ratio as controls, based on age, dominanthand, etiology, Neer typing, glenohumeral joint dislocation, rotator cuff integrity, and osteoporosis T-score. The primary RTSA group included 12 males and 36 females, with a mean age of 76.38±6.15 years (range, 65-87 years). Clinical indicators including demographic characteristics, healing rate of the greater tuberosity, visual analogue score (VAS), Constant-Murley score, American Shoulder and Elbow Surgeons (ASES), shoulder range of motion (ROM), patient satisfaction, and complication rate were collected and analyzed.Results:The mean follow-up duration was 40(32, 60) months (range, 25-72 months) in the primary RTSA group and 38(30, 61) months (range, 24-68 months) in RTSA revision group. There was no significant difference (χ 2=5.058, P=0.168) in the healing rate of the greater tuberosity between the primary RTSA group (41/48, 85.4%) and the RTSA revision group (15/24, 62.5%). Compared with preoperative status, the ROM of anterior elevation, abduction supination, external rotation, VAS score, Constant-Murley score, and ASES score were significantly improved at the last follow-up (all P<0.05) in the RTSA revision group. The anterior elevation (123.74°± 16.57°), abduction supination (113.73°±16.42°), and external rotation (36.45°±10.36°) in the primary RTSA group were superior to those in the RTSA revision group (109.43°±18.75°, 98.64°±15.47°, 30.47°±10.64°, respectively), the difference was statistically significant ( P<0.05). No statistical difference of ROM of internal rotation between the two groups was found (χ 2=4.034, P=0.133). At the last follow-up, the Constant-Murley scores (75.47±11.66) and ASES scores (73.58±15.72) of the primary RTSA group were higher than those in the RTSA revision group (60.43±10.24 and 63.28±18.77, respectively), and the differences were statistically significant ( P<0.05). In terms of VAS (1.66±0.93 vs. 2.02±1.15) and patient satisfaction [83%(40/48) vs. 88%(21/24)], no statistical difference was identified ( P>0.05). The complication rate were 10.4% (5/48) in the primary RTSA group and 20.8% (5/24) in the RTSA revision group (χ 2=1.452, P=0.285), with no serious complications requiring revision surgery in either group. Conclusions:For elderly patients with proximal humeral fractures after failed operation, RTSA revision might effectively improve the limb function and alleviatepain. However, compared with RTSA revision, primary RTSA demonstrated superiorearly clinical outcomes in shoulder ROM and functional recovery.

Objective:To evaluate the clinical outcomesof primary reverse total shoulder arthroplasty (RTSA) and revision procedure with RTSA after treatment failure of complex proximal humeral fractures in the elderly.Methods:A retrospective analysis was conductedon 24 elderly patients with Neer three- or four-part proximal humeral fractures who underwent RTSA revision after treatment failure (RTSA revision group) from January 2017 to June 2022. There were 7 males and 17 females included, with a mean age of 78.23±5.78 years (range, 67-86 years). Forty-eight patients who underwent primary RTSA (primary RTSA group) during the same time period were selected by propensity score matchingin a 1∶2 ratio as controls, based on age, dominanthand, etiology, Neer typing, glenohumeral joint dislocation, rotator cuff integrity, and osteoporosis T-score. The primary RTSA group included 12 males and 36 females, with a mean age of 76.38±6.15 years (range, 65-87 years). Clinical indicators including demographic characteristics, healing rate of the greater tuberosity, visual analogue score (VAS), Constant-Murley score, American Shoulder and Elbow Surgeons (ASES), shoulder range of motion (ROM), patient satisfaction, and complication rate were collected and analyzed.Results:The mean follow-up duration was 40(32, 60) months (range, 25-72 months) in the primary RTSA group and 38(30, 61) months (range, 24-68 months) in RTSA revision group. There was no significant difference (χ 2=5.058, P=0.168) in the healing rate of the greater tuberosity between the primary RTSA group (41/48, 85.4%) and the RTSA revision group (15/24, 62.5%). Compared with preoperative status, the ROM of anterior elevation, abduction supination, external rotation, VAS score, Constant-Murley score, and ASES score were significantly improved at the last follow-up (all P<0.05) in the RTSA revision group. The anterior elevation (123.74°± 16.57°), abduction supination (113.73°±16.42°), and external rotation (36.45°±10.36°) in the primary RTSA group were superior to those in the RTSA revision group (109.43°±18.75°, 98.64°±15.47°, 30.47°±10.64°, respectively), the difference was statistically significant ( P<0.05). No statistical difference of ROM of internal rotation between the two groups was found (χ 2=4.034, P=0.133). At the last follow-up, the Constant-Murley scores (75.47±11.66) and ASES scores (73.58±15.72) of the primary RTSA group were higher than those in the RTSA revision group (60.43±10.24 and 63.28±18.77, respectively), and the differences were statistically significant ( P<0.05). In terms of VAS (1.66±0.93 vs. 2.02±1.15) and patient satisfaction [83%(40/48) vs. 88%(21/24)], no statistical difference was identified ( P>0.05). The complication rate were 10.4% (5/48) in the primary RTSA group and 20.8% (5/24) in the RTSA revision group (χ 2=1.452, P=0.285), with no serious complications requiring revision surgery in either group. Conclusions:For elderly patients with proximal humeral fractures after failed operation, RTSA revision might effectively improve the limb function and alleviatepain. However, compared with RTSA revision, primary RTSA demonstrated superiorearly clinical outcomes in shoulder ROM and functional recovery.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective To initially explore the possibility of applying the fluorescence micro-optical sectioning tomography(fMOST)high-resolution 3D reconstruction system to the morphological study of the intestinal nervous system and to preliminarily establish a method for studying the morphology of the intestinal nervous system using this system.Methods fMOST high-resolution 3D reconstruction system was used to study the intestinal nervous system of C57BL/6 mice in detail.Based on this method,a new morphological method of the visceral nervous system of small animal models was explored at the single-cell level.Results Compared with the large intestine,the small intestine lacked the typical myenteric plexus(Auerbach),deep mucosal plexus(Henley),and submucosal superficial plexus(Meissner).Conclusion The result of this paper provide a clearer and systematic display of the anatomical structure of the enteric nervous system in C57BL/6 mice,and further clarify the similarities and differences between the enteric nervous system of mice and human,and provide a theoretical basis for its rational application in the study of digestive system diseases.The morphological study of fMOST high-resolution 3D reconstruction system is not limited to the central nervous system,but can be extended to the morphological study of multiple visceral nervous systems.

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

BACKGROUND: Congenital heart disease (CHD) is a leading cause of birth defect-related mortality. However, more recent CHD mortality data for China are lacking. Additionally, limited studies have evaluated sex, rural-urban, and region-specific disparities of CHD mortality in China. METHODS: We designed a population-based study using data from the Dataset of National Mortality Surveillance in China between 2008 and 2021. We calculated age-adjusted CHD mortality using the sixth census data of China in 2010 as the standard population. We assessed the temporal trends in CHD mortality by age, sex, area, and region from 2008 to 2021 using the joinpoint regression model. RESULTS: From 2008 to 2021, 33,534 deaths were attributed to CHD. The period witnessed a two-fold decrease in the age-adjusted CHD mortality from 1.61 to 0.76 per 100,000 persons (average annual percent change [AAPC] = -5.90%). Females tended to have lower age-adjusted CHD mortality than males, but with a similar decline rate from 2008 to 2021 (females: AAPC = -6.15%; males: AAPC = -5.84%). Similar AAPC values were observed among people living in urban (AAPC = -6.64%) and rural (AAPC = -6.12%) areas. Eastern regions experienced a more pronounced decrease in the age-adjusted CHD mortality (AAPC = -7.86%) than central (AAPC = -5.83%) and western regions (AAPC = -3.71%) between 2008 and 2021. Approximately half of the deaths (46.19%) due to CHD occurred during infancy. The CHD mortality rates in 2021 were lower than those in 2008 for people aged 0-39 years, with the largest decrease observed among children aged 1-4 years (AAPC = -8.26%), followed by infants (AAPC = -7.01%). CONCLUSIONS CHD mortality in China has dramatically decreased from 2008 to 2021. The slower decrease in CHD mortality in the central and western regions than in the eastern regions suggested that public health policymakers should pay more attention to health resources and health education for central and western regions.
Humans ; Heart Defects, Congenital/mortality* ; Male ; Female ; China/epidemiology* ; Infant ; Child, Preschool ; Adult ; Child ; Adolescent ; Infant, Newborn ; Middle Aged ; Young Adult ; Aged ; Rural Population