ObjectiveTo investigate the effects of Huanglian Jiedutang （HLJDT） on cognitive function in mice with ischemic stroke （IS） and to elucidate whether its neuroprotective effects are mediated by inhibition of the nuclear factor-κB （NF-κB） signaling pathway and subsequent suppression of NF-κB-regulated neuronal apoptosis. MethodsAn IS model was established using middle cerebral artery occlusion （MCAO）. Sixty C57BL/6J mice were randomly assigned to five groups （n =12 per group）， i.e.， sham operation， model， HLJDT low-dose （3.9 g·kg^-1·d^-1）， HLJDT high-dose （7.8 g·kg^-1·d^-1）， and Ginkgo biloba extract （GBE， 31.2 mg·kg^-1·d^-1）. Post-operatively， neurological deficit scores （Longa score）， cerebral infarct volume assessed by 2，3，5-triphenyltetrazolium chloride （TTC） staining， and brain water content were evaluated. Learning and memory were assessed using new object recognition （NOR） and fear conditioning （FC） tests. Hippocampal pathology was examined via hematoxylin and eosin （HE） staining. Immunofluorescence detected expression of glial fibrillary acidic protein （GFAP， astrocyte marker）， cellular oncogene Fos （c-Fos， neuronal activation marker）， and glutamate decarboxylase 65 （GAD65）. Western blot measured nuclear factor-κB inhibitor protein α （IκBα）， phosphorylated IκBα （p-IκBα）， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， ionic calcium binding adapter molecule 1 （Iba-1）， tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and apoptosis-related proteins， such as cleaved cysteinyl aspartate-specific protease 3 （Caspase-3）， B-cell lymphoma 2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Real-time quantitative PCR （Real-time PCR） was used to assess mRNA levels of Iba-1， TNF-α， IL-1β， NF-κB p65， cleaved Caspase-3， Bax， and Bcl-2. ResultsCompared with the sham group， the model group exhibited significantly increased neurological deficit scores， brain water content， and cerebral infarct volume （P<0.01）. Hippocampal CA1 neurons were disorganized， showing nuclear pyknosis and karyolysis. NOR exploration time and FC freezing time were significantly reduced （P<0.01）. GFAP and c-Fos expression were increased， while GAD65 expression was decreased （P<0.01）. Cleaved Caspase-3 and Bax were upregulated， Bcl-2 was downregulated， and the Bax/Bcl-2 ratio was elevated （P<0.01）. Expression levels of p-IκBα， p-NF-κB p65， IL-1β， TNF-α， and Iba-1 were significantly increased （P<0.01）. Compared with the model group， HLJDT high-dose， low-dose， and GBE groups showed significant improvements in all parameters （P<0.01）. Among them， the HLJDT high-dose group showed the most pronounced neuronal structural recovery and superior performance in NOR and FC tests （P<0.01）. In this group， GFAP and c-Fos decreased， GAD65 increased （P<0.01）， apoptosis-related protein expression was reversed， and NF-κB signaling and related inflammatory factor expression were suppressed （P<0.01）. ConclusionHLJDT ameliorates cognitive dysfunction in mice after IS， potentially by inhibiting the NF-κB signaling pathway， thereby reducing neuroinflammation and hippocampal neuronal apoptosis.

To report diagnosis and treatment of a patient with rectal cancer and synchronous liver metastases, accompanied by severe coronary artery stenosis and cardiac insufficiency, and to provide a reference for clinical decision-making in such cases through introducing the treatment contradiction, the choice of systemic treatment plan and the timing of operation, and the final outcome. After definitive diagnosis, the patient received systemic therapy with cetuximab＋irinotecan＋oxaliplatin＋raltitrexed, and along with oral medication to improve cardiac function, followed by elective coronary revascularization. After revascularization, the cardiac function of patient was fully improved. And the tumor lesion was effectively controlled after antitumor therapy. Once the cardiac condition of patient stabilized, two-stage surgical resection of the primary rectal cancer and liver metastases was performed, ultimately achieving tumor-free status, and discharged.

ObjectiveTo explore the mechanisms of Qingchang Wenzhong Decoction （清肠温中方， QWD） in treating ulcerative colitis （UC）. MethodsA total of 100 male C57BL/6J mice were assigned to a pseudo-germ-free group （n=45） and a conventional group （n=55） using a random number table. Pseudo-germ-free model was established by giving antibiotic treatment and subsequently subjected to acute UC induction. After the model was successfully established， the 45 pseudo-germ-free acute UC mice were randomly allocated to a pseudo-germ-free model group， a pseudo-germ-free QWD group， and a pseudo-germ-free mesalazine group， with 15 mice in each group. The 55 conventional mice were randomly divided into a normal control group （n=10）， as well as a conventional model group， a conventional QWD group， and a conventional mesalazine group， with 15 mice in each group. Except for the normal control group， acute UC models were established in all other groups. Mice in the control group received no intervention. From day 32 of the experiment， mice in the pseudo-germ-free QWD group and the conventional QWD group were administered with QWD granules at a dose of 9.71 g/（kg·d） by gavage with deionized water， while those in the pseudo-germ-free mesalazine group and the conventional mesalazine group were given mesalazine enteric-coated tablets at a dose of 151.67 mg/（kg·d） by gavage. Mice in the remaining groups received an equal volume of deionized water once daily for 7 consecutive days. On day 25 of the experiment， six mice were randomly selected from both the pseudo-germ-free group and the conventional group to measure body weight， and fecal samples were collected for 16S rDNA sequencing to compare differences in gut microbiota， including operational taxonomic units （OTUs）， Shannon index， Observed_species index， and phylogenetic diversity （PD whole tree）. On day 39， body weight was measured in all groups， and the disease activity index （DAI） was evaluated. Colon length and colon wet weight were recorded. Histopathological changes in colonic tissues were assessed by hematoxylin and eosin （HE） staining， and histological injury scores were determined. In addition， the expression levels of mucopolysaccharides and mucin 2 （MUC2） in colonic tissues were measured. ResultsOn day 25， there was no significant difference in body weight between the pseudo-germ-free group and the conventional microbiota group （P＞0.05）. Compared to the conventional microbiota group， the pseudo-germ-free group showed significantly reduced OTUs， Shannon index， Observed_species index， and PD whole tree （P＜0.01）. On day 39， compared to the normal control group， mice in the conventional model group showed a significant decrease in the body weight and an increase in DAI， along with increased colon wet weight， shortened colon length， markedly elevated histopathological scores， and reduced expression of mucopolysaccharides and MUC2 （P＜0.01）. In contrast， no significant differences were observed in these parameters in the pseudo-germ-free model group （P＞0.05）. Compared to the conventional model group， the conventional QWD group showed significant improvement in all measured parameters， whereas the conventional mesalazine group showed reductions only in DAI scores and colon wet weight （P＜0.01）. No statistically significant differences were observed among the pseudo-germ-free model group， the pseudo-germ-free QWD group， and the pseudo-germ-free mesalazine group （P＞0.05）. ConclusionQWD may promote the reconstruction of the intestinal mucus barrier by regulating the intestinal flora， thereby exerting a therapeutic effect on acute UC.

ObjectiveTo explore the mechanisms of Qingchang Wenzhong Decoction （清肠温中方， QWD） in treating ulcerative colitis （UC）. MethodsA total of 100 male C57BL/6J mice were assigned to a pseudo-germ-free group （n=45） and a conventional group （n=55） using a random number table. Pseudo-germ-free model was established by giving antibiotic treatment and subsequently subjected to acute UC induction. After the model was successfully established， the 45 pseudo-germ-free acute UC mice were randomly allocated to a pseudo-germ-free model group， a pseudo-germ-free QWD group， and a pseudo-germ-free mesalazine group， with 15 mice in each group. The 55 conventional mice were randomly divided into a normal control group （n=10）， as well as a conventional model group， a conventional QWD group， and a conventional mesalazine group， with 15 mice in each group. Except for the normal control group， acute UC models were established in all other groups. Mice in the control group received no intervention. From day 32 of the experiment， mice in the pseudo-germ-free QWD group and the conventional QWD group were administered with QWD granules at a dose of 9.71 g/（kg·d） by gavage with deionized water， while those in the pseudo-germ-free mesalazine group and the conventional mesalazine group were given mesalazine enteric-coated tablets at a dose of 151.67 mg/（kg·d） by gavage. Mice in the remaining groups received an equal volume of deionized water once daily for 7 consecutive days. On day 25 of the experiment， six mice were randomly selected from both the pseudo-germ-free group and the conventional group to measure body weight， and fecal samples were collected for 16S rDNA sequencing to compare differences in gut microbiota， including operational taxonomic units （OTUs）， Shannon index， Observed_species index， and phylogenetic diversity （PD whole tree）. On day 39， body weight was measured in all groups， and the disease activity index （DAI） was evaluated. Colon length and colon wet weight were recorded. Histopathological changes in colonic tissues were assessed by hematoxylin and eosin （HE） staining， and histological injury scores were determined. In addition， the expression levels of mucopolysaccharides and mucin 2 （MUC2） in colonic tissues were measured. ResultsOn day 25， there was no significant difference in body weight between the pseudo-germ-free group and the conventional microbiota group （P＞0.05）. Compared to the conventional microbiota group， the pseudo-germ-free group showed significantly reduced OTUs， Shannon index， Observed_species index， and PD whole tree （P＜0.01）. On day 39， compared to the normal control group， mice in the conventional model group showed a significant decrease in the body weight and an increase in DAI， along with increased colon wet weight， shortened colon length， markedly elevated histopathological scores， and reduced expression of mucopolysaccharides and MUC2 （P＜0.01）. In contrast， no significant differences were observed in these parameters in the pseudo-germ-free model group （P＞0.05）. Compared to the conventional model group， the conventional QWD group showed significant improvement in all measured parameters， whereas the conventional mesalazine group showed reductions only in DAI scores and colon wet weight （P＜0.01）. No statistically significant differences were observed among the pseudo-germ-free model group， the pseudo-germ-free QWD group， and the pseudo-germ-free mesalazine group （P＞0.05）. ConclusionQWD may promote the reconstruction of the intestinal mucus barrier by regulating the intestinal flora， thereby exerting a therapeutic effect on acute UC.

Objective To develop a risk assessment scale for immune checkpoint inhibitor (ICI)-associated myocarditis based on multidisciplinary collaboration, and to evaluate its diagnostic performance. Methods Based on multidisciplinary cooperation, integrating clinical experience from oncology and cardiology, literature data, and patient conditions, a risk assessment scale for ICI-associated myocarditis was developed. A total of 101 patients with malignancies who received immunotherapy at Zhongshan Hospital, Fudan University, from October 2020 to October 2024 were included as the validation cohort. Patients were stratified into low-risk (0-1 point), medium-risk (2-4 points), and high-risk (≥5 points) groups based on their scale scores. The association between pretictive risk stratifications and actual assessment results was assessed using the Cox proportional hazards regression model. The predictive value of the scale for ICI-associated myocarditis was evaluated using receiver operating characteristic (ROC) curve. Agreement between the scale scores and actual assessment results was assessed using Cohen’s Kappa coefficient. Results Based on the scale pretictive results, 28(27.7%), 8(7.9%), 65(64.4%) patients were at low risk, medium risk, and high risk for ICI-related myocarditis, respectively; however, 46(45.5%), 8(7.9%), 47(46.5%) were at low risk, medium risk, and high risk actually. Kaplan-Meier survival analysis showed that the cumulative incidence of ICI-related myocarditis in the high-risk group was significantly higher than that in the medium- and low-risk groups (P＜0.05). In the multivariable-adjusted Cox proportional hazards model, the ICI-related myocarditis risk in high-risk group was about 4 times that in the low-risk group. ROC curve analysis demonstrated that the average area under the curve (AUC) for predicting ICI-related myocarditis was 0.81, with an accuracy of 0.74. The Cohen’s Kappa coefficient was 0.55, indicating moderate agreement. In the actual high-risk group, no patient was predicted to be at low risk; in the actual low-risk group, 16 patients were predicted to be at high risk. Conclusions This risk assessment scale for ICI-associated myocarditis shows high predictive performance. It provides oncologists with a simple yet effective multidisciplinary diagnostic reference tool, potentially enhancing early identification of ICI-associated myocarditis.

Objective:To evaluate the effectiveness and safety of minimally invasive anchoring hook intraocular lens (IOL) interscleral suture fixation surgery.Methods:A cohort study was conducted.A total of 74 patients (74 eyes) with aphakia, artificial lens dislocation, or lens dislocation were included at Tengzhou Central People's Hospital from 2021 to 2022.According to the surgical method, the patients were divided into conventional fixation group (39 cases, 39 eyes) undergoing conventional intraocular lens suspension surgery and anchoring hook fixation group (35 cases, 35 eyes) undergoing minimally invasive anchoring hook type IOL interscleral suture fixation surgery.Surgical time, preoperative best corrected visual acuity (BCVA) before surgery and at 1 day and 1 month after surgery, corneal endothelial cell density before and at 1 month after surgery, mislocation of the artificial IOL and the incidence of complications were recorded.This study was reviewed and approved by the Ethics Committee of Tengzhou Central People's Hospital (No.2019-20), and all patients signed the informed consent form.Results:One day and 1 month after surgery, the BCVA of the anchoring hook fixation group was better than that of the conventional fixation group, and the differences were statistically significant (both P<0.05). The preoperative corneal endothelial cell densities of the anchor hook fixation group and conventional fixation group were (2 431±556) and (2 406±625)cells/mm 2, and the postoperative 1-month corneal endothelial cell densities were (2 012±703) and (2 004±759)cells/mm 2, respectively, without statistically significant difference (both P>0.05). The average surgical time of the anchoring hook fixation group was (67.1±7.2) minutes, which was significantly shorter than (93.1±17.9) minutes of the conventional fixation group, and the difference was statistically significant ( t=13.654, P<0.001). During the 1-month follow up, no IOL mislocation occurred in the two groups, and two eyes in the routine fixation group developed anterior chamber hemorrhage, accounting for 5.1%, no anterior chamber bleeding occurred in the anchoring hook fixation group.Corneal edema was observed in 6 eyes and 1 eye of the conventional fixation group and anchor hook fixation group, accounting for 15.4% and 2.9%, respectively.Macular edema was observed in 2 eyes of the conventional fixation group, accounting for 5.1%, and no macular edema occurred in the anchoring hook fixation group.Throughout the entire follow-up, there was no case of low intraocular pressure, ciliary detachment, exposed sutures, or requiring secondary surgical intervention in either group. Conclusions:Both minimally invasive anchoring hook IOL intrascleral suture fixation and conventional IOL suspension are safe and effective.Compared with conventional IOL suspension surgery, anchoring hook IOL intrascleral suture fixation surgery has more advantages in postoperative visual recovery, shorter surgical operation time and a lower incidence of postoperative complications.

Objective:To explore the changes of atlantoaxial joint spaces and pharyngeal airway after combined orthodontic-orthognathic treatment in skeletal class Ⅲ patients with mandibular deviation.Methods:A total of 34 adult skeletal class Ⅲ patients (10 males and 24 females) with mandibular deviation who received combined orthodontic-orthognathic treatment at the Department of Orthodontics and the Department of Orthognathic Surgery in the Stomatological Hospital of Chongqing Medical University from August 2014 to October 2021 were retrospectively selected. The patients were 22 (5) years old (18-33 years). Cone-beam CT data of patients taken before treatment (T0), after preoperative orthodontics (T1), and 6 to 12 months after orthognathic surgery (T2) were collected. The anterior atlanto-dental interval (ADI), variance of bilateral lateral atlanto-dental interval (VBLADI), the anterior posterior length (APL), maximum transverse width (LTW), aspect ratio (L/W), cross-sectional area (CSA) of each airway cross-section, the airway volumes, as well as the positions of the maxillofacial landmark points [subspinale (point A), supramental (point B), posterior nasal spine (point PNS), the most anterior and superior point of the hyoid bone (point H)] were measured at different time points. The correlations between airway changes, maxillofacial movements as well as the changes in the atlantoaxial joint spaces were also analyzed.Results:During the combined orthodontic-orthognathic treatment, no statistically significant differences were found in the ADI and VBLADI among different treatment time points (all P>0.05). After preoperative orthodontics, the volume of total airway increased from 20 868 (6 669) mm 3 to 21 302 (8 911) mm 3 ( P<0.05). After orthognathic surgery, there were no statistically significant differences in the APL, CSA of the PNS plane, the L/W of the uvula plane, and the nasopharyngeal airway volume compared with those after preoperative orthodontics (all P>0.05). The L/W of the PNS plane after surgery was significantly increased compared with that after preoperative orthodontics ( P<0.05), while other airway parameters were all significantly decreased compared with those after preoperative orthodontics (all P<0.05). Compared with before treatment, the nasopharyngeal airway volume after surgery [6 186 (1 707) mm3] increased significantly ( P<0.05) and the palatopharyngeal airway volume [8 145 (2 594) mm3] and the glossopharyngeal airway volume [5 605 (4 395) mm3] decreased significantly (all P<0.05). There was no statistically significant difference in the total airway volume between after surgery and before treatment ( P>0.05). Correlation analysis showed that after preoperative orthodontics, the amount of the sagittal movement of point B was moderately positively correlated with the total airway volume change ( r=0.40, P=0.022). Before and after orthognathic surgery, the amount of the sagittal movement of point PNS was moderately positively correlated with the changes in the palatopharyngeal airway volume and the total airway volume ( r=0.43, P=0.015; r=0.46, P=0.008). In addition, the change in VBLADI before and after orthognathic surgery was weakly positively correlated with the changes in the CSA of the PNS plane and the APL of the uvula plane ( r=0.35, P=0.029; r=0.38, P=0.016). Conclusions:During the combined orthodontic-orthognathic treatment, the anterior atlanto-dental interval in skeletal class Ⅲ patients with mandibular deviation remained stable among different treatment time points. The total airway volume increased after preoperative orthodontics. After orthognathic surgery, the backward movement of the mandible tended to reduce the size of the pharyngeal airway, and the morphology of the glossopharyngeal airway tended to become more flattened. The changes in the pharyngeal airway dimensions were correlated with the maxillomandibular movements and the atlantoaxial joint space changes.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

AIM:To investigate the potential mechanisms by which cell division cycle protein 42(Cdc42)regulates endothelial-mesenchymal transition(EndMT)in pulmonary hypertension(PH).METHODS:The pulmonary hypertension(PH)model was established using Sugen-5416 combined with hypoxia.Twenty-four C57BL/6 mice were ran-domly divided into four groups:normoxia control(CON)group,normoxia+ML141(CON+ML141)group,Sugen-5416+hypoxia(SuHx)group,and SuHx+ML141 group,with 6 mice in each group.After 4 weeks,right ventricular systolic pressure(RVSP)and cardiac ultrasound parameters were measured,and lung tissues were collected for immunofluores-cence staining.Pulmonary microvascular endothelial cells(PMVECs)were isolated using magnetic bead sorting.Calcium imaging was performed to assess Ca2+signaling,and Western blot was used to detect EndMT-related proteins as well as stromal interaction molecule 1(STIM1)and Orai1 expression.RESULTS:In the SuHx group,mice exhibited signifi-cantly increased RVSP,Fulton index(right ventricle/left ventricle+septum),end-diastolic right ventricular free wall thick-ness(RVEDWT),and end-systolic right ventricular free wall thickness(RVESWT)(P<0.01).Conversely,pulmonary artery acceleration time/pulmonary artery ejection time(PAT/PET)and tricuspid annulus plane systolic excursion(TAPSE)were significantly reduced(P<0.01).The Cdc42 inhibitor ML141 ameliorated these changes.The SuHx group exhibited a significant decrease in CD31 fluorescence intensity in pulmonary vascular endothelial cells(P<0.01),a marked increase in α-smooth muscle actin(α-SMA)fluorescence intensity in smooth muscle cells(P<0.01),and the emergence of CD31/α-SMA co-localization.These alterations were reversed by ML141.Hypoxia induced EndMT in PM-VECs,characterized by decreased CD31 and vascular endothelial cadherin(VE-cadherin)along with increased α-SMA and vimentin(P<0.01),which was suppressed by ML141(P<0.01).Hypoxia activated store-operated calcium entry(SOCE),enhancing intracellular Ca2? release,extracellular Ca2? influx,and basal Ca2? levels(P<0.01),while upregulat-ing STIM1 and Orai1 expression(P<0.01).These changes were reversed by ML141.Furthermore,both ML141 and STIM1 knockdown inhibited the upregulation of EndMT-related transcription factors Snail and Twist(P<0.05).CON-CLUSION:Cdc42 may participate in EndMT in PH by regulating store-operated calcium channels in pulmonary microvas-cular endothelial cells.

Background and purpose:Approximately 30%of patients with metastatic colorectal cancer(CRC)develops pulmonary metastasis,yet less than 10%are eligible for surgical resection.Radiofrequency ablation(RFA)serves as an alternative therapy for non-surgical candidates,but the relationship between its efficacy and tumor diameter remains controversial.This study aimed to investigate the impact of tumor size on survival outcomes and local progression risk in CRC patients with pulmonary metastasis after RFA,and to validate the clinical utility of a 3 cm threshold for prognosis.Methods:This retrospective study included CRC patients with pulmonary metastasis who underwent RFA at Fudan University Shanghai Cancer Center between January 2016 and December 2024.Patients were stratified into two groups based on maximum lesion diameter:≤3 cm(Small group)and 3-5 cm(Large group).Patient inclusion criteria:⑴ pathologically confirmed lung metastases originating from CRC,with metastases limited to the lungs or extra-pulmonary metastatic lesions having been radically treated;⑵ maximum lesion diameter<5 cm;⑶complete clinical data available;⑷ complete imaging data available,including computed tomography(CT)images during ablation and contrast-enhanced CT images during postoperative follow-up;⑸ follow-up time of at least＞6 months after RFA;⑹ technical complete ablation;⑺ fewer than 3 pulmonary metastatic lesions.Exclusion criteria:⑴ target lesions previously treated with local therapies such as RFA or radiotherapy;⑵ patients unable to tolerate RFA;⑶ patients with follow-up time＜6 months after RFA.Three senior interventional physicians performed percutaneous RFA under guidance of a 64-slice spiral CT scanner.Chest contrast-enhanced CT scans obtained 1 month after RFA were used as the baseline,followed by contrast-enhanced CT scans every 3 months for 1 year,then every 6 months for subsequent follow-up.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(ethical approval number:2108241-11).Primary endpoints included overall survival(OS),progression-free survival(PFS),and local tumor progression(LTP).Kaplan-Meier analysis and multivariate COX regression were employed to evaluate the independent prognostic value of tumor size.Results:A total of 134 patients who met the inclusion criteria were ultimately enrolled,including 77 in the Small group and 57 in the Large group.With a median follow-up of 35 months,the≤3 cm group demonstrated superior 1-,3-,and 5-year OS rates(100.0%,95.1%,74.2%)compared to the 3-5 cm group(94.7%,36.8%,27.0%,P＜0.0001),and the≤3 cm group demonstrated superior 1-,3-,and 5-year PFS rates(90.9%,34.4%,23.3%)compared to the 3-5 cm group(13.8%,0.0%,0.0%,P＜0.000 1).The≤3 cm group also exhibited significantly lower 1-,3-,and 5-year LTP rates(0.0%,19.7%,33.6%)compared to the 3-5 cm group(46.0%,75.5%,75.5%,P＜0.000 1).Multivariable analysis identified tumor diameter＞3 cm as an independent predictor of worse OS[hazard ratio(HR)=6.49,95%CI:3.18-13.24,P＜0.001],while elevated preoperative carcinoembryonic antigen(CEA)(≥5 ng/mL)correlated with shorter OS(HR=1.82,P=0.033).Conclusion:CRC patients with pulmonary metastasis and tumor diameters of 3-5 cm exhibited significantly inferior survival outcomes after RFA compared to the≤3 cm group.A tumor diameter of 3 cm can serve as a critical threshold for selecting RFA indications,and combining preoperative CEA levels can optimize patient stratification.