Hepatic alveolar echinococcosis is a highly invasive zoonotic parasitic disease with poor prognosis. Surgical intervention serves as the pivotal approach to achieve radical cure and improve the prognosis of hepatic alveolar echinococcosis patients. In recent years, with the popularization of the concept of precision surgery and the development of the multidisciplinary diagnosis and treatment model, the surgical treatment strategies for hepatic alveolar echinococcosis have been continuously enriched, and the selection of surgical procedures has become increasingly diversified. Although key surgical techniques such as radical hepatectomy, autologous liver transplantation and allogeneic liver transplantation have achieved remarkable progress in clinical application, many insurmountable challenges still remain. Therefore, by sorting out the latest evidence-based advances in the field of surgical treatment for hepatic alveolar echinococcosis, this article focuses on discussing the application status and bottlenecks of radical hepatectomy, autologous liver transplantation and allogeneic liver transplantation in hepatic alveolar echinococcosis, aiming to provide a reference for the clinical treatment of hepatic alveolar echinococcosis.

ObjectiveThe present study aimed to investigate alterations in white matter microstructure and spontaneous neural activity in male college smokers, and to further explore their associations with nicotine dependence. Given that adolescence and early adulthood represent critical periods for brain maturation, particularly for white matter development, understanding the neural correlates of smoking behavior during this stage is of substantial importance for both neuroscience and public health. MethodsA total of 115 male undergraduate students were initially recruited for this study. After quality control and exclusion procedures, 52 male college smokers and 42 demographically matched healthy non-smokers were included in the final analysis. All participants underwent multimodal magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI). White matter fiber tracts were reconstructed using the automated fiber quantification (AFQ) method, which enables precise identification and quantification of major fiber bundles. Eighteen major white matter tracts were segmented for each participant. Along the core trajectory of each tract, 100 equidistant nodes were sampled. Fractional anisotropy (FA) was calculated at each node to assess white matter microstructural integrity, while amplitude of low-frequency fluctuation (ALFF) was computed to evaluate spontaneous neural activity within white matter tracts. Between-group differences in FA and ALFF were assessed using two-sample t-tests, with appropriate corrections applied for multiple comparisons. Furthermore, Pearson correlation analyses were conducted to examine the relationships between imaging-derived metrics (FA and ALFF values in regions showing significant group differences) and nicotine dependence severity, as measured by the Fagerström test for nicotine dependence (FTND). ResultsCompared with healthy non-smokers, male college smokers exhibited significantly increased FA values in several white matter tracts, including the left thalamic radiation, right corticospinal tract, forceps major of the corpus callosum, left uncinate fasciculus, and right arcuate fasciculus. These findings suggest altered microstructural organization or increased directional coherence within these pathways. In addition, smokers demonstrated significantly elevated ALFF values in the forceps major, right uncinate fasciculus, and left arcuate fasciculus, indicating enhanced spontaneous neural activity in these white matter regions. Correlation analyses revealed that FA values in the left thalamic radiation and right corticospinal tract were negatively correlated with FTND scores, suggesting that higher levels of nicotine dependence were associated with reduced microstructural integrity or altered fiber organization in these regions. In contrast, ALFF values in the forceps major and right uncinate fasciculus were positively correlated with FTND scores, indicating that greater nicotine dependence was associated with increased spontaneous neural activity in specific white matter pathways. ConclusionThe present study provides evidence that male college smokers exhibit distinct alterations in both white matter microstructure and functional activity. These abnormalities are not uniformly distributed but rather localized to specific fiber tracts implicated in sensorimotor processing, interhemispheric communication, and higher-order cognitive and emotional regulation. Importantly, the observed associations between imaging metrics and nicotine dependence severity suggest that these structural and functional alterations may reflect neurobiological mechanisms underlying addiction. The combination of AFQ-based tract profiling and multimodal MRI offers a sensitive approach for detecting subtle changes along white matter pathways, highlighting its potential utility in identifying neuroimaging biomarkers of nicotine dependence. Overall, these findings indicate that smoking during early adulthood may disrupt ongoing white matter maturation, potentially leading to long-term consequences for brain function. This study provides novel insights into the neural basis of nicotine dependence and underscores the importance of early intervention and prevention strategies targeting young smokers.

The purpose of this study was to establish a luciferase immunosorbent assay(LISA)using the Crimean-Congo hemorrhagic fever virus(CCHFV)glycoprotein C(Gc),a specific antigen,for the detection of CCHFV IgG antibodies.Three antigenic fragments based on CCHFV glycoprotein C were designed,and three recombinant plasmids were constructed by liga-tion with the NanoLuc luciferase(NLuc)expression vector pNLF1-N through molecular cloning.The accuracy of the sequences in the recombinant plasmids was confirmed through sequencing.The recombinant plasmids were transfected into eukaryotic cells to obtain fusion proteins containing specific antigens and luciferase,and the expression of the fusion proteins was verified by western blotting,thereby facilitating the establishment of the CCHFV-LISA detection technique.The assay's sensitivity,specificity,and stability were evaluated and compared with those of a commercial CCHFV IgG antibody test kit.Three recom-binant antigen fragments of CCHFV Gc—NLuc-Gc-Full,NLuc-Gc-C1,and NLuc-Gc-C2—were expressed,with molecular weights of 80.1 kDa,62.8 kDa,and 53.9 kDa,respectively.The optimal fragment for CCHFV detection was NLuc-Gc-C2.The sensitivity of the CCHFV-LISA was 90.9％,and the specificity was 100％;the findings were highly concordant with those for the commercial CCHFV enzyme-linked immunosorbent assay kit.Repeatability tests indicated no statistically significant differ-ences in inter-and intra-assay variability within the same batch.The LISA was highly specific,sensitive,and user-friendly in detecting IgG antibodies against the CCHFV.Therefore,this method may facilitate serological diagnosis and epidemiological studies in endemic regions,and provide essential technical support for disease surveillance and early warning.

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

Objective To analyze the reasons for the failure of subject screening in clinical trials of antineoplastic drugs and the impact of natriuretic criteria on the entry of subjects into clinical trials,to explore the strategies to improve the suc-cessful enrolment of screened subjects,and to provide reference bases for research institutes and sponsors in the formulation of na-triuretic criteria.Methods This study selected data from 40 drug clinical trials conducted at the Drug Clinical Trial Research Center of the Cancer Hospital of the Chinese Academy of Medical Sciences from January 1,2016,to June 30,2022.It statistically described the collected data on the frequency and percentage composition of screening failures among participants and the inclu-sion and exclusion criteria in the protocols.Results A total of 425 subjects were screened out of 40 clinical trial programmers covering 8 tumor types,with the majority being＜65 years of age(333,78.4％),of which the most important reasons included vol-untary withdrawal(71,16.7％),tumor metastasis(52,12.2％),failure to recover from treatment of pre-existing disease(38,8.9％),failure of bone marrow function(19,4.5％),and non-compliant liver function(15,3.5％).Among the nadir indicators,the age of the subjects(100％),ECOG score(97.5％),bone marrow function(ANC:95.0％,PLT:97.5％,HB:97.5％),liver function(T-BiL:95.0％,ALT:87.5％,AST:95.0％),renal function(CR:80.0％),and viral screening(HIV:80.0％,HBV:70.0％,HCV:62.5％)were relatively stringent.Conclusion The main reasons for subject screening failure in clinical trials in oncology in our hospital are voluntary withdrawal,brain metastasis,and failure of their biochemical test standards,which are close-ly related to the setting of clinical trial nadir criteria.Therefore,an in-depth understanding of subjects'characteristics,accurate set-ting of appropriate nadir criteria,continuous improvement of trial design,and strengthening of communication with subjects to pro-vide more relevant information will help to improve the screening success rate of clinical trials.

Objective To evaluate the quality of cisatracurium besilate injection produced by domestic manufacturers.Methods A comprehensive evaluation of 104 batches of samples was carried out using statutory testing methods combined withexploratory research,including related substances,1,5-pentanediol diacrylate,residual solvents,genotoxic impurities of benzenesulfonate esters,infrared spectrum,and endotoxin examination.The quality of domestic products and the controllability of current specifications were comprehensively evaluated.Results According to the statutory tests,the qualified rate of 104 batches of samples was 100.0％.The exploratory research showed that the results of related substances in the samples produced by 6 manufacturers were far below the limit,and no genotoxic impurities of benzenesulfonate esters were detected.However,the results showed that there was variability in 1,5-pentanediol diacrylate,as well as residual solvents.Conclusions The quality of the cisatracurium besilate injection is good,and the current specifications should be further improved and unified.It was proposed that the infrared spectrum,related substance,and 1,5-pentanediol diacrylate method be added or revised,and the limit of endotoxin strictly controlled.It was proposed that manufacturers pay attention to the quality of API and control injection production.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Objective:To evaluate the effects of a reduced-positioning restrictions nursing program on postoperative recovery, sleep quality, self-care ability, and hip joint function in patients undergoing total hip arthroplasty (THA), providing a reference for postoperative positioning management.Methods:A randomized controlled trial was conducted, and 140 THA patients admitted to Zhejiang Provincial People′s Hospital from January 2022 to June 2023 were selected using convenience sampling. They were divided into a control group (70 cases) and an observation group (70 cases) using a random number table. The control group received conventional rehabilitation care, while the observation group received a reduced-positioning restrictions nursing program in addition to the conventional care. The incidence of dislocation at 3 months postoperatively, the activities of daily living, the hip joint function recovery at 1 month and 3 months postoperatively, the sleep quality at 1 month postoperatively were compared between the two groups.Results:Finally 63 cases in the control group and 64 cases in the observation group completed the study. The control group included 25 males and 38 females, with an average age of (65.44 ± 10.97) years, while the observation group included 28 males and 36 females, with an average age of (65.13 ± 12.18) years. At 3 months postoperatively, there was no significant difference in the dislocation rate between the control group and the observation group ( P>0.05). At 1 month and 3 months postoperatively, the scores of activities of daily living in the observation group were (77.89 ± 6.71) and (93.52 ± 6.59) points respectively, which were higher than those in the control group [(69.68 ± 5.53) and (87.38 ± 7.72) points], the differences were statistically significant ( t=5.38, 6.96, both P<0.05), the time, interaction and inter-group effects were all statistically significant ( F=33.93, 10.81, 876.91, all P<0.05). At 1 month postoperatively, the excellent and good rate of hip joint function score grade in the observation group was 73.44% (47/64), which was higher than 41.27% (26/63) in the control group, the difference was statistically significant ( Z=-3.67, P<0.05), there was no statistically significant difference between the two groups at 3 months postoperatively ( P>0.05). At 1 month after the operation, the excellent and good rate of sleep quality score grades in the observation group was 81.25% (52/64), which was higher than 57.14% (36/63) in the control group, and the difference was statistically significant ( Z=-3.00, P<0.05). Conclusions:Incorporating a reduced-positioning restrictions nursing program into the perioperative management of THA does not increase the risk of prosthesis dislocation. This approach enhances patient comfort, improves sleep quality, increases self-care ability, and supports the recovery of hip joint function.

Objective To investigate the initial temperature sensation and pressure pain sensation in patients receiving invisible or-thodontic treatment.Methods Twenty-two patients receiving clear aligner treatment(experimental group)and 22 volunteers(control group)participated.Perceptual changes were assessed using the visual analogue scale(VAS)and quantitative sensory testing(QST).The QST employed in this study included warm detection threshold/heat pain threshold(WDT/HPT),cold detection threshold/cold pain threshold(CDT/CPT),and pressure pain threshold(PPT).Tests were conducted on teeth 21 and 31,their gums,the left hand,and the left masseter muscle.Assessments occurred at baseline,2 hours,24 hours,7 days,and 28 days after aligner placement.Re-sults In the experimental group,VAS scores peaked at 24 hours and then significantly decreased(P＜0.01).For teeth 21 and 31,the WDT and HPT of the labial attached gingiva,along with the PPT of these teeth,showed significant decreases at 24 hours and 7 days compared to baseline and the control group(P＜0.01).At 24 hours and 7 days,VAS scores were negatively correlated with the WDT and HPT of the labial attached gingiva of teeth 21 and 31(P＜0.05).Conclusion At 24 hours and 7 days post-clear aligner treatment,thermal sensitivity and pain,as well as pressure pain sensitivity,increased for the gingiva of teeth 21 and 31.Thermal sensitivity was also correlated with pain intensity.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.