The benefit of postoperative adjuvant therapy for patients with resectable esophageal squamous cell carcinoma (ESCC) is not yet supported by high-level evidence. This review analyzes the role of adjuvant therapy by examining the discrepancy between clinical needs and guidelines, its historical evolution, recent advances in high-risk factors, and future outlooks. We provide a detailed discussion of high-risk factors used for patient selection, including lymph node positivity, and for node-negative patients, features such as tumor length, location, T stage, extent of lymph node dissection, differentiation, vascular and neural invasion, laboratory indices, and molecular markers. The goal is to inform the development of individualized precision treatment strategies for resectable ESCC.

By systematically sorting out the theoretical origin， manipulation key points， and clinical applications of sparrow-pecking needling， it is believed that sparrow-pecking needling method involves performing small-amplitude， high-frequency lifting and thrusting of the needle tip in the original position， with heavy thrusting and light lifting， starting slowly and then becoming rapid， thus forming a characteristic needling sensation that spreads to the surroundings in a wavelike manner. The sparrow-pecking needling plays a role in stimulating the conduction of channel qi and regulating the circulation of qi and blood. Additionally， this paper summarized the clinical applications of sparrow-pecking needling in five aspects， regulating mind， regulating channel sinews， regulating zang-fu organs， regulating ying-wei （nutrient and defense qi）， and regulating yang qi， so as to provide references for inheriting and expanding the theory and clinical application of sparrow-pecking needling.

Objective:To investigate the risk factors and preventive strategies for post laparoscopic one-stage ap-pendectomy for fatty liquefaction(OIH)in pediatric appendiceal abscesses.Methods:170 children with appendiceal ab-scess who underwent laparoscopic one-stage surgery to remove the appendix in Jiaozuo Maternal and Child Health Hospital,Henan Province,from January 2021 to December 2024 were selected for the study.The first 100 cases were included in the training set,patients were divided into the non-OIH group(n=66)and the OIH group(n=34)according to whether OIH occurred in the postoperative period.According to the same criteria,the latter 70 children with appendiceal abscess were included in the validation set,including 44 in the non-OIH group and 26 in the OIH group.Univariate and multivariate logistic regression was applied to analyse the factors influencing postoperative OIH.Stepwise regression was used to assess the importance of each factor,and the factors were ranked according to the Akaike Information Cri-teria(AIC).A risk prediction model for postoperative OIH was constructed and evaluated by strong influence point analy-sis,ROC curve,calibration curve,and decision curve.Results:In the training and validation sets,the differences in general information such as fat thickness,use of high-frequency electrocautery,incision cleaning,Hb,WBC,Alb,HbA1c,and comorbid underlying diseases between the non-OIH and OIH groups were statistically significant(P<0.05).The re-sults of multivariate logistic regression analysis showed that fat thickness,use of high-frequency electrosurgical knife,incision cleaning,Hb,WBC,Alb,HbA1c,and co-morbid underlying diseases were independent influences on OIH(P<0.05).Fat thickness,Alb,and use of HFD were most strongly associated with postoperative OIH,and the multifactorial model consisting of fat thickness,Alb,and use of HFD model had a good value for assessing the risk assessment of postoperative OIH,and had a high predictive value.The strong influence point analyses of the regression model rows showed that the Cook distances were all less than 1,i.e.,there were no data points in the modelled data that signifi-cantly influenced the estimation of model parameters.the area under the ROC curve(AUC)was 0.925(95%CI:0.887～0.953),i.e.,the model had good discriminatory ability.The model calibration curve was nearly a diagonal line,implying that the predicted probability was approximately equal to the actual probability,and the calculated Brier value=0.095,in-dicating that the model had good predictive ability.The decision curves of the predictive model were higher than the 2 extreme curves for threshold probabilities of 0.1 to 0.9,i.e.,the net benefit of the predictive model was higher.Conclu-sion:Fat thickness,Alb levels,and high-frequency electrosurgical knife use showed a strong association with postop-erative OIH.A multifactorial model constructed from fat thickness,Alb levels,and high-frequency electrocautery knife use demonstrated good efficacy in assessing the risk of OIH after laparoscopic one-stage appendectomy for pediatric appendiceal abscess.

Opium is obtained by air-drying the milky latex extracted from the unripe capsules of the opium poppy(Papaver somniferum).This latex is rich in benzylisoquinoline alkaloids(BIA),with major active compounds in-cluding morphine,codeine,thebaine,papaverine,and noscapine.Compound licorice oral solution and compound licorice tablets are derivative drugs containing opium.Initially classified as over-the-counter(OTC)medications,both formulations were later reclassified as prescription drugs by the National Medical Products Administration(NMPA),restricting their purchase without proper authorization.Although the national pharmacopeia standards specify the morphine content in the opium raw materials used for compound licorice oral solution and tablets,they lack mandatory requirements for the detection and quantification of the other four major alkaloids.Given the unique nature of opium raw materials and the stringent regulatory requirements for such drugs,it is imperative to enhance and refine simultaneous detection and control methods for all alkaloid components in these products.Furthermore,the establishment of scientific and reasonable detection and control standards for preservatives in compound licorice formulations is crucial to improving overall product quality management and ensuring drug safety and efficacy.This study analyzes and discusses the quality standards,detection methods,and research progress for opium and com-pound licorice preparations,aiming to explore the potential for technological innovation and ensure the safe use of these medications.

Objective:To investigate the neural regulatory mechanism of parvalbumin-positive interneurons(PV-INs)in the dentate gyrus(DG)involved in the impairment of spatial recognition memory by exercise-induced chronic fatigue.Methods:Male Sprague-Dawley(SD)rats were divided into control group and fatigue group by random num-ber method.A three-level incremental load treadmill training program was selected to establish a chronic exhaustion exercise fatigue model.The spatial recognition memory ability of rats was tested by novel object recognition test.The ac-tivation levels and quantitative changes of astrocytes(AS)and PV-INs in the DG region was observed and quantified through immunofluorescence staining and immunohistochemical staining.The phosphorylation level of calcium/calmodu-lin-dependent protein kinase Ⅱ(CaMK Ⅱ)in the hippocampus was detected by Western blot.Results:In the test of novel object recognition,the exploration time of novel object was reduced in the fatigue group,and the discrimination index was significantly lower than that in the control group(P＜0.01).Immunohistochemical staining showed that PV-INs in the DG region of fatigue rats were lighter and fewer than those in the control group,the fibers were short and sparse,and the positive cell density and average optical density of cells were significantly lower than those in the control group(P＜0.01).Immunofluorescence staining showed that AS was significantly activated,glial fibrillary acidic pro-tein(GFAP)was stained deeply,and the cell processes were dense and elongated in the DG region of fatigue rats.The positive cell density and mean fluorescence intensity were significantly higher than those of the control group(P＜0.01).The results of Western blot showed that the phosphorylation level of CaMK Ⅱ protein in the hippocampus of the fatigue group was significantly reduced than that of the control group(P＜0.01).Conclusion:Exercise-induced chro-nic fatigue inhibited PV-INs in the rat hippocampal DG region.The excessive activation of AS following exercise fatigue may be a major contributor to this PV-INs suppression.Concurrently,reduced phosphorylation levels of CaMK Ⅱ protein were observed in hippocampal tissue.These alterations ultimately impaired spatial recognition memory in the rats.

AIM:To investigate the role of BRCA2 and CDKN1A interacting protein(BCCIP)in gastric can-cer(GC)and elucidate its mechanism in mediating cisplatin resistance.METHODS:The BCCIP mRNA expression was assessed in GC tissues(n=415)and normal tissues(n=34)using The Cancer Genome Atlas(TCGA)database.In an in-ternal cohort(n=36 for RT-qPCR;n=5 for Western blot;n=30 for immunohistochemistry),BCCIP expression at both mRNA and protein levels was examined in GC tissues and paired adjacent normal tissues.Human GC cell lines AGS and HGC27 were cultured in vitro and treated with cisplatin in a dose(0,2,4,6,8 and 10 μmol/L)-and time(0,6,24 and 48 h)-dependent manner,followed by Western blot analysis of BCCIP expression.Stable BCCIP knockdown cell lines(shRNA#1 and shRNA#2 groups)were generated via lentiviral transfection,with empty vector-transfected cells serving as controls(vector group).Flow cytometry and colony formation assay were performed to evaluate the effects of BCCIP on apoptosis and colony-forming ability of GC cells treated with cisplatin.Western blot was utilized to detect the changes of BCCIP protein expression levels in the cytoplasm and nucleus of GC cells after cisplatin(2.5 and 1.0 μmol/L)treatment,as well as the effects of BCCIP on the expression of DNA damage marker γ-H2AX and apoptosis-related proteins cleaved caspase-9 and cleaved caspase-3,and the activation of checkpoint kinase 1(CHK1)after cisplatin(2.5 and 1.0 μmol/L)treatment.Immunofluorescence was conducted to observe the effect of BCCIP on γ-H2AX expression in GC cells treated with cisplatin(2.5 and 1.0 μmol/L).RESULTS:The BCCIP expression was significantly up-regulated in GC tissues compared with normal tissues(P<0.01).Cisplatin induced up-regulation of BCCIP expression in a dose-and time-depen-dent manner.Knockdown of BCCIP significantly enhanced cisplatin-induced apoptosis(P<0.01)and reduced colony-forming ability(P<0.05)of GC cells.Knockdown of BCCIP promoted the expression of γ-H2AX,but inhibited the activa-tion of CHK1 after cisplatin treatment,with increased protein levels of cleaved caspase-9 and cleaved caspase-3(P<0.01).CONCLUSION:Cisplatin promotes the expression of BCCIP in GC cells.BCCIP confers cisplatin resistance in GC cells by suppressing apoptosis through modulation of DNA damage response pathways.

A total of 1 159 measles cases were reported in Zhuhai City from 2005 to 2022, with an average annual incidence rate of 4.21/10 5 (0-30.51/10 5). The M( Q1, Q3) age of the cases was 6.10 years old (10 months,23.20 years old), with the youngest cases being 2 months and the oldest age of 55 years old. The distribution of cases by age group was as follows: individuals aged18 years and older (34.94%), 8-23 months (22.95%), 2-6 years old (16.74%), 7-17 years old(12.86%) and infants under 8 months (12.51%), respectively. The primary groups affected by the disease included scattered children, workers, and students. The regional distribution exhibited distinct clustering characteristics in urban areas or streets with a high concentration of the migrant population. Following the initiation of Measles-containing Vaccine Supplementary Immunization Activities (MCV SIA) in 2009, the incidence of measles in Zhuhai City has significantly decreased, and there is no evident seasonal distribution of cases.

Objective:To explore the effects of early electroacupuncture(EA)intervention on the high mobility group box 1(HMGB1)/Toll-like receptor 4(TLR4)signaling pathway-related protein expression and oligodendrocytes in mice with amyotrophic lateral sclerosis(ALS),and uncover the potential molecular mechanisms underlying the improvement of motor function in ALS mice by early EA intervention.Methods:ALS mice carrying the SOD1G93A gene were randomly divided into a model group and an EA group,with 10 mice in each group;10 littermate mice with a negative SOD1G93A genotype served as the control group.In the EA group,Baihui(GV20),Tianzhu(BL10),and Tianshu(ST25)were selected with needles retained for 10 min,5 consecutive days per week,with 2 days of rest.One week constituted a course of treatment,and a total of 3 consecutive courses were performed.The other groups were grasped and fixed similarly,but without intervention.Motor function was assessed using the open field test(OFT)and Morris water maze(MWM).Subsequently,hematoxylin-eosin staining was used to observe neuron morphology in the M1 region of the cerebral cortex.Immunofluorescence was performed to detect the positive cell rate of TAR DNA-binding protein 43(TDP-43),and double immunofluorescence staining was used to observe the positive cell rate and cell states of ionized calcium-binding adaptor molecule 1(Iba-1)and myelin basic protein(MBP)in the M1 region of the cerebral cortex.Western blotting was used to detect the relative expression levels of TDP-43,tumor necrosis factor(TNF)-α,HMGB1,and TLR4 proteins.Results:Compared to the control group,the model group exhibited a reduced total movement distance in the OFT,and an increased escape latency,as well as fewer platform crossings in the MWM,with statistically significant differences(P<0.01).In the model group,the number of degenerated and necrotic neurons in the M1 region of the ALS mouse cerebral cortex increased,with significant nuclear shrinkage and cytoplasmic vacuolization;the percentage of TDP-43 immunofluorescence positive cells in the M1 region of the cerebral cortex increased(P<0.01),and the relative expression level of TDP-43 protein in the cerebral cortex showed a significant increase(P<0.01);the Iba-1 positive cell percentage increased,while the MBP positive cell percentage decreased(P<0.01);the relative expression levels of TNF-α,HMGB1,and TLR4 proteins increased(P<0.05).Compared to the model group,the EA group showed an increased total movement distance(P<0.01),and a reduced escape latency,and more platform crossings in the MWM,with statistically significant differences(P<0.05).In the EA group,neurons showed improvement,with reduced degeneration and necrosis,and larger,clearer nuclei;the percentage of TDP-43 immunofluorescence positive cells in the M1 region of the cerebral cortex decreased(P<0.05),and the relative expression level of TDP-43 protein also decreased(P<0.05);the percentage of Iba-1 positive cells in the M1 region of the cerebral cortex decreased,while the percentage of MBP positive cells increased(P<0.01);the relative expression levels of TNF-α,HMGB1,and TLR4 proteins decreased(P<0.05).Conclusion:EA intervention can suppress microglial activation,improve the state of oligodendrocytes,and reduce abnormal TDP-43 aggregation in the M1 region of the cerebral cortex in ALS model mice;its mechanism of action may be related to the HMGB1/TLR4 signaling pathway.

Objective:To investigate the neural regulatory mechanism of parvalbumin-positive interneurons(PV-INs)in the dentate gyrus(DG)involved in the impairment of spatial recognition memory by exercise-induced chronic fatigue.Methods:Male Sprague-Dawley(SD)rats were divided into control group and fatigue group by random num-ber method.A three-level incremental load treadmill training program was selected to establish a chronic exhaustion exercise fatigue model.The spatial recognition memory ability of rats was tested by novel object recognition test.The ac-tivation levels and quantitative changes of astrocytes(AS)and PV-INs in the DG region was observed and quantified through immunofluorescence staining and immunohistochemical staining.The phosphorylation level of calcium/calmodu-lin-dependent protein kinase Ⅱ(CaMK Ⅱ)in the hippocampus was detected by Western blot.Results:In the test of novel object recognition,the exploration time of novel object was reduced in the fatigue group,and the discrimination index was significantly lower than that in the control group(P＜0.01).Immunohistochemical staining showed that PV-INs in the DG region of fatigue rats were lighter and fewer than those in the control group,the fibers were short and sparse,and the positive cell density and average optical density of cells were significantly lower than those in the control group(P＜0.01).Immunofluorescence staining showed that AS was significantly activated,glial fibrillary acidic pro-tein(GFAP)was stained deeply,and the cell processes were dense and elongated in the DG region of fatigue rats.The positive cell density and mean fluorescence intensity were significantly higher than those of the control group(P＜0.01).The results of Western blot showed that the phosphorylation level of CaMK Ⅱ protein in the hippocampus of the fatigue group was significantly reduced than that of the control group(P＜0.01).Conclusion:Exercise-induced chro-nic fatigue inhibited PV-INs in the rat hippocampal DG region.The excessive activation of AS following exercise fatigue may be a major contributor to this PV-INs suppression.Concurrently,reduced phosphorylation levels of CaMK Ⅱ protein were observed in hippocampal tissue.These alterations ultimately impaired spatial recognition memory in the rats.

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude