Objective To investigate the effect of ubiquitin specific peptidase 22 (USP22) on the occurrence and development of esophageal squamous cell carcinoma (ESCC) under hypoxic conditions, and its regulatory relationship with hypoxia-inducible factor-1α (HIF-1α). Methods Western blotting and quantitative polymerase chain reaction were used to detect the differences in USP22 protein and mRNA expression between normal esophageal epithelial cells HEEC and ESCC cell lines KYSE30, KYSE150, EC9706, and TE-1 under normoxic (5% CO2, 20% O2, 75% N2) and hypoxic (5% CO2, 1% O2, 94% N2) conditions. By transfecting USP22 plasmid or siUSP22, ESCC cells were divided into a normoxia control group, a normoxia+USP22 group, a normoxia+siUSP22 group, a hypoxia control group, a hypoxia+USP22 group, and a hypoxia+siUSP22 group. The proliferation and migration abilities of cells in each group were detected. The expression of USP22 and HIF-1α under hypoxic conditions after up-regulating or down-regulating USP22 was detected, and their regulatory relationship was verified. The interaction between USP22 and HIF-1α was verified by co-immunoprecipitation (Co-IP) technique. Results Compared with HEEC cells, the expression of USP22 in ESCC cells was significantly increased (P<0.05). Up-regulation of USP22 expression promoted the proliferation and migration of ESCC cells, while silencing USP22 inhibited the proliferation and migration of ESCC cells (P<0.05). Under hypoxic conditions, the expression of USP22 and HIF-1α increased, and with the up-regulation of USP22 expression, the expression of HIF-1α also significantly increased (P<0.05). Co-IP experiment confirmed the binding between USP22 and HIF-1α. Conclusion Up-regulation of USP22 expression promotes the proliferation and migration of ESCC cells. Hypoxia microenvironment can induce the increase of USP22 expression in ESCC. USP22 may participate in the regulation of the occurrence and development of ESCC by directly binding to HIF-1α.

ObjectiveTo investigate the differences in the regulatory effects of formulas containing Ephedrae Herba and Armeniacae Semen Amarum （Mahuangtang， Sanaotang， and Maxing Shigantang） on thermosensitive transient receptor potential ion channels （thermo TRPs） in the mouse model of asthmatic airway inflammation. MethodsSixty female C57BL/6 mice were allocated into blank， model， dexamethasone （0.75 mg·kg^-1）， Mahuangtang （3.8 g·kg^-1）， Sanaotang （2.8 g·kg^-1）， and Maxing Shigantang （6.6 g·kg^-1） groups （n=10）. The mouse model of asthma was established with ovalbumin （OVA） and treated with normal saline （blank group） or corresponding drugs （10 mL·kg^-1）， once a day， 19-28 days after modeling. The levels of eosinophils （EOS） in peripheral blood and white blood cell （WBC） in bronchoalveolar lavage fluid （BALF）， changes in enhanced pause （Penh）， and pathological damage of lung tissue were observed in each group. Western blot and real-time PCR were employed to quantify the protein and mRNA levels， respectively， of high-temperature thermosensitive channels （TRPV1 and TRPV3） and low-temperature thermosensitive channels （TRPA1 and TRPM8） in the lung tissue. ResultsCompared with the blank group， the model group showed a typical asthma phenotype， including elevations in the level of EOS in peripheral blood， level of WBC in BALF， and value of Penh （P<0.05，P<0.01）， and severe lung tissue damage. Compared with the model group， the three formulas alleviated the asthma phenotype to varying degrees （P<0.05，P<0.01）. Compared with the blank group， the model group showed up-regulated protein levels of TRPV1 and TRPA1 in the lung tissue （P<0.01）. Compared with the model group， Maxing Shigantang and Sanaotang groups showed down-regulated protein levels of TRPV1 and TRPA1 （P<0.05， P<0.01）. Moreover， Maxing Shigantang and Sanaotang groups showed more significant down-regulation in protein levels of TRPV1 and TRPA1， respectively （P<0.01）， while no obvious regulatory effect was observed in the Mahuangtang group. Compared with those in the blank group， the protein levels of TRPV3 and TRPM8 were up-regulated in the model group （P<0.01）. Compared with the model group， Maxing Shigantang and Sanaotang down-regulated the protein levels of TRPV3 and TRPM8 （P<0.01）. Moreover， Maxing Shigantang and Sanaotang exerted stronger down-regulating effects on TRPV3 （P<0.05） and TRPM8 （P<0.01）， respectively. Compared with the blank group， the model group presented up-regulated mRNA levels of TRPV1， TRPV3， TRPA1， and TRPM8 in the lung tissue （P<0.01）， and such up-regulations were significantly decreased by Maxing Shigantang and Sanaotang （P<0.01）. Moreover， Maxing Shigantang outperformed Sanaotang in regulating high-temperature thermosensitive channels TRPV1 and TRPV3 （P<0.05， P<0.01）. The regulation effect of the， Maxing Shigantang on high-temperature thermosensory channel proteins of TRPV1 and TRPV3 was better than that of the Sanaotang P<0.05P<0.01while the Sanaotang outperformedhad a significant regulatory effect on Maxing Shigantang in regulating the low-temperature thermosensory thermosensitive channel proteins of TRPA1 and TRPM8which was better than that of the Maxing Shigantang （P<0.05，P<0.01）. ConclusionThe experimental results showed that Mahuangtang， Sanaotang， and Maxing Shigantang all had protective effects on asthma airway inflammation.while Mahuangtang did not show the regulatory effect on TRPV1 and or TRPA1. Maxing Shigantang preferred to regulate high-temperature thermosensory thermosensitive channels of TRPV1 and TRPV3 channels， and Sanaotang preferred to regulate low-temperature thermosensory thermosensitive channels of TRPA1 and TRPM8.

Elderly patients with lung cancer have a significantly increased risk of perioperative cardiopulmonary complications due to physiological decline, high incidence of complications and reduced surgical tolerance, which directly affects postoperative recovery and long-term survival. Although the concepts of minimally invasive surgery and enhanced recovery after surgery have improved clinical outcomes, early recognition and intervention of postoperative complications in elderly patients remains a significant challenge in the field of thoracic surgery. By integrating recent literature and clinical practice, this paper systematically analyzes the pathophysiological mechanism and risk factors of perioperative cardiopulmonary complications in elderly patients with lung cancer, and discusses individualized intervention strategies based on risk stratification and multidisciplinary team, in order to provide theoretical basis and practical guidance for optimizing perioperative management and improving postoperative prognosis in elderly patients.

Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

Objective: To investigate the association between brain and muscle Arnt like protein 1( BMAL 1) gene and ambulatory blood pressure (ABP) parameters in college students, and to explore the influence of the interaction between the gene and weight status on the ABP levels, so as to provide reference for early prevention of chronic cardiovascular diseases related to hypertension. Methods: During September 2022 to June 2024, a total of 510 college students were recruited from a university in Changsha, China for on site questionnaire investigation, physical examination, ABP monitoring and genotyping testing. Multiple linear regression method was used to explore the association between the BMAL 1 gene and ABP indicators. An interaction term was included in the general linear model of multiple linear regression to analyze the interactive effects of BMAL 1 gene polymorphisms and weight status on ABP levels. Results: The prevalence of abnormal 24 hour blood pressure, abnormal daytime blood pressure, and abnormal nighttime blood pressure were 3.3%, 3.1%, and 3.9%, respectively. Multiple linear regression analysis showed that the BMAL 1/rs7950226 polymorphism was positively correlated with the 24 hour diastolic blood pressure(DBP) and the daytime DBP level after adjusting for gender, age, and body mass index( β =0.87,0.99, both P <0.05). Also, interaction between BMAL 1/ rs 11022775 and weight status on the nighttime DBP level ( P interaction =0.03) was found. The CC genotype carriers had significantly higher nighttime DBP level ( β =3.52, P <0.05) among overweight/obesity college students, but no differences in nocturnal DBP levels were observed between CC genotype carriers and TT+CT genotype carriers among college students with normal body weight( P > 0.05). Conclusions The rs 7950226 polymorphism is associated with 24 hours DBP and daytime DBP levels. Significant interaction between rs 11022775 with weight status on the nighttime DBP level is found among college students.

The American College of Radiology recently published the appropriateness criteria for initial imaging assessment of chronic pancreatitis （CP） and acute inflammation superimposed on CP （ACP）. These criteria systematically elaborate on the role of various imaging modalities in diagnosing CP and ACP， assessing disease severity， identifying underlying causes， and evaluating complications， in order to provide guidance for effective management of CP patients through early and accurate imaging techniques and with reference to clinical and laboratory assessments. This article gives an excerpt of the key statements from the criteria.

Objective To investigate the predictive value of edema metabolic and hematoma dynamics changes on motor and cog-nitive recovery outcomes in patients with intracerebral hemorrhage(ICH).Methods The CT data of ICH patients were collected to evaluate hematoma volume changes from admission to day 3.On day 3,multivoxel magnetic resonance spectroscopy(MRS)was per-formed with region of interest located in the edema region and contralateral normal tissue.Motor and cognitive function recovery was assessed using the simplified F-M scale and the Montreal cognitive assessment(MoCA)on day 3 and at the 3-month follow-up,respec-tively.Overall clinical outcomes were assessed using the Glasgow outcome scale(GOS),and all patients were divided into good and poor outcome groups.Clinical data and metabolic differences in the edema region between the two groups were compared,respec-tively.Logistic regression analysis and receiver operating characteristic(ROC)curves were used to identify and evaluate independent prognostic factors.Subgroup analysis were performed via stratification of hematoma location.Results The logistic regression analy-sis indicated that intraventricular extension,hematoma changes,and the ratio of N-acetyl aspartate(NAA)around the hematoma to contralateral normal brain parenchyma NAA(rNAA)were inde-pendent prognostic factors for poor outcomes(P＜0.05).The area under the curve(AUC)for each factor and the combined model were 0.69,0.73,0.79,and 0.82,respectively.In patients with ICH in the basal ganglia region,△F-M was negatively correlated with hematoma changes and positively correlated with rNAA value(P＜0.001).In patients with ICH in the thalamic and lobar regions,△MoCA was not significantly correlated with hematoma changes(P＞0.05),but was positively correlated with rNAA value(P＜0.001).Conclusion The rNAA holds predictive value for motor and cognitive recovery outcomes following standard treatment.

Objective To explore the potential role and underlying mechanism of the functionally uncharacterized gene Gm49394 on regulating β-cell apoptosis under diabetic conditions.Methods The expression and translational activity of Gm49394 in pancreatic β-cell lines and non-β-cell lines were validated using RNA fluorescence in situ hybridization(RNA-FISH),quantitative real-time PCR(qPCR),Western blotting,and immunofluorescence(IF)assay.The β-cell lines(NIT-1/Min6)with Gm49394 overexpression or knockdown were constructed.The proliferation,apoptosis,mitochondrial function,as well as oxidative stress and endoplasmic reticulum stress markers in these β-cell lines under physiological homeostasis or pathological stress conditions,such as high glucose(30 mmol/L),inflammation(10 ng/mL IFN-γ alone or combined with 10 ng/mL IL-6),and hydrogen peroxide(100 μmol/L H2O2)were detected by flow cytometry and Western blotting.Results RNA-FISH and qPCR indicated that Gm49394 was specifically expressed in pancreatic β-cell lines and up-regulated under high glucose or inflammatory stimulation.IF assay and Western blotting showed that Gm49394 had protein-coding activity.Flow cytometry and Western blotting identified that Gm49394 overexpression did not affect β-cell proliferation,but promoted β-cell apoptosis and increased reactive oxygen species(ROS)and mitochondrial superoxide(MitoSOX)levels in β cells under physiological homeostasis or pathological stress conditions(P<0.05).Under physiological conditions,Gm49394 knockdown failed to induce significant alterations on β-cell apoptosis,ROS,or MitoSOX levels.Under pathological stress conditions,Gm49394 knockdown significantly suppressed β-cell proliferation,apoptosis,as well as oxidative and endoplasmic reticulum stress(P<0.05).Conclusion Gm49394 may promote β-cell apoptosis via oxidative stress and endoplasmic reticulum stress.

OBJECTIVE: To observe the effects of moxibustion at different temperatures on cognitive function and blood glucose levels in patients with cognitive impairment associated with type 2 diabetes mellitus (T2DM). METHODS: A total of 66 T2DM patients with cognitive impairment were randomly assigned to a high-temperature group (22 cases, 1 case dropped out, 1 case was eliminated), a medium-temperature group (22 cases, 2 cases were eliminated), and a low-temperature group (22 cases, 2 cases were eliminated). All groups received moxibustion at Baihui (GV20), Dazhui (GV14), and Shenting (GV24) based on their existing glycemic control treatment. Moxibustion temperatures were maintained at 44-46 ℃ (high-temperature group), 41-43 ℃ (medium-temperature group), and 38-40 ℃ (low-temperature group), respectively, for 20 min per session, every other day, 3 times a week for 3 months. The Montreal cognitive assessment (MoCA) score, mini-mental state examination (MMSE) score, short-term memory (STM) accuracy and average reaction time, Rey-Osterrieth complex figure (ROCF) score, fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) were assessed before and after treatment. Clinical efficacy was evaluated after treatment. RESULTS: After treatment, MMSE scores in all three groups were higher than those before treatment (P<0.05). In the high-temperature group, the total MoCA score and the scores of visuospatial and executive function, memory and delayed recall, attention, naming, language, and abstraction were higher than those before treatment (P<0.05); the scores of ROCF copy, immediate recall, and delayed recall were higher than those before treatment (P<0.05); the HbA1c level was lower than that before treatment (P<0.05). In the medium-temperature group, the total MoCA score and the scores of memory and delayed recall, attention, and language were higher than those before treatment (P<0.05). STM accuracy was higher than before treatment (P<0.05), and STM average reaction time was shorter than before treatment (P<0.05) in both the high-temperature and medium-temperature groups. After treatment, the total MoCA score and the scores of visuospatial and executive function, memory and delayed recall, attention, and language in the high-temperature group were higher than those in the medium- and low-temperature groups (P<0.05); MMSE score, STM accuracy, and ROCF immediate recall and delayed recall scores were higher than those in the medium- and low-temperature groups (P<0.05); STM average reaction time was shorter than that in the medium- and low-temperature groups (P<0.05); HbA1c level was lower than that in the low-temperature group (P<0.05). The total MoCA score, attention score, and MMSE score in the medium-temperature group were higher than those in the low-temperature group (P<0.05), and STM average reaction time was shorter than that in the low-temperature group (P<0.05). There were no statistically significant differences in FPG within or between the three groups before and after treatment (P>0.05). The total effective rates were 75.0% (15/20) in the high-temperature group, 50.0% (10/20) in the medium-temperature group, and 15.0% (3/20) in the low-temperature group; the total effective rate in the high-temperature group was significantly higher than that in the low-temperature group (P<0.05). CONCLUSION Moxibustion at different temperatures has a dose-effect relationship in treating cognitive impairment in T2DM patients. A temperature range of 44-46 ℃ is more effective in improving cognitive function and stabilizing average blood glucose levels over 2-3 months.
Humans ; Diabetes Mellitus, Type 2/therapy* ; Male ; Female ; Moxibustion ; Middle Aged ; Aged ; Cognitive Dysfunction/psychology* ; Cognition ; Temperature ; Blood Glucose/metabolism* ; Adult ; Acupuncture Points

Objective To explore the diagnostic value of endoscopic grading of gastric intestinal metaplasia (EGGIM) score under acetic acid-enhanced narrow band imaging (AA-NBI) observation mode for gastric intestinal metaplasia (GIM). Methods A total of 120 patients who underwent gastroscopy at Jinshan Hospital of Fudan University from February 2022 to February 2023 were selected. All patients underwent both white light and AA-NBI endoscopy, with photographic records of intestinal metaplasia in five areas: greater curvature of antrum, lesser curvature of antrum, greater curvature of corpus, lesser curvature of corpus and incisura. EGGIM score was performed: 0 for no intestinal metaplasia, 1 point for focal intestinal metaplasia (GIM area ratio≤30%), 2 points for extensive intestinal metaplasia (GIM area ratio＞30%), with a total score of 10 points. Targeted biopsies were performed on suspicious GIM lesions found during endoscopy. If no suspicious GIM lesions were observed, random biopsies were performed according to the updated Sydney system. The pathological histological examination results were staged based on the operative link on gastric intestinal metaplasia assessment (OLGIM) system. The diagnostic value of EGGIM score for OLGIM stage Ⅲ-Ⅳ patients was evaluated using receiver operating characteristic (ROC) curves. Results The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of AA-NBI in detecting GIM were 96.3%, 91.6%, 94.5%, 95.0%, and 93.6%, respectively. The area under the ROC curve for EGGIM diagnosing OLGIM stage Ⅲ-Ⅳ was 0.952 (95%CI 0.914-0.990). The optimal cut-off value for EGGIM was 5 points, with a sensitivity of 96.7% (95%CI 87.6%-99.4%) and specificity of 88.1% (95%CI 76.5%-94.7%). Conclusions EGGIM score (≥5 points) under AA-NBI mode has good diagnostic capability for patients with OLGIM stage Ⅲ-Ⅳ.