Objective To explore the value of 18F-fluorodeoxyglucose(18F-FDG)PET/CT in predicting the stage of untreated elderly esophageal cancer.Methods The clinical data of 83 esophageal cancer patients who had not received any treatment were ret-rospectively analyzed,including age,body mass index(BMI),lesion length and width,TNM stage,and clinical stage.Spearman correlation analysis was used to evaluate the correlation between TNM stage and clinical stage and the maximum standardized uptake value(SUVmax)of the primary tumor.Linear correlation analysis was used to evaluate the correlation between age,BMI,lesion length and width,and SUVmax.The receiver operating characteristic(ROC)curve of the primary tumor SUVmax in predicting the newly diagnosed elderly esophageal cancer T3-T4 stage and clinical stage Ⅲ-Ⅳ was plotted,the area under the curve(AUC)was obtained,and the best cut off value of the primary tumor SUVmax in the diagnosis of T3-T4 stage and clinical stage Ⅲ-Ⅳ was obtained.Results The T stage and clinical stage were positively correlated with the SUVmax of the primary tumor(r=0.688,P<0.001;r=0.313,P=0.004),while the N stage,M stage,lesion location,age,BMI,lesion length and width were not correlated with the SUVmax(P>0.05).There were significant differences in SUVmax between the T1-T2 stage and the T3-T4 stage,as well as between the clinical stageⅠ-Ⅱ and the Ⅲ-Ⅳ(P<0.05).According to the analysis of ROC curve,the AUC for diagnosing T3-T4 stage and clinical stageⅢ-Ⅳ with the SUVmax of the primary tumor were 0.904[95%confidence interval(CI)0.835-0.973]and 0.700(95%CI 0.570-0.829),respectively,with cut off values of 12.40 and 12.70.The sensitivities were 0.918 and 0.708,respectively,and the specificities were 0.712 and 0.729,respectively.Conclusion 18F-FDG PET/CT primary tumor SUVmax has a good predictive value for the diagnosis of untreated elderly esophageal cancer before treatment of T3-T4 stage and clinical stage Ⅲ-Ⅳ,which can improve the accuracy of esophageal cancer stage.

Neoadjuvant therapy has become the standard treatment for locally advanced resectable esophageal cancer, significantly improving long-term survival compared to surgery alone. Neoadjuvant therapy has evolved to include various strategies, such as concurrent chemoradiotherapy, chemotherapy, immunotherapy, or targeted combination therapy. This enriches clinical treatment options and provides a more personalized and scientific treatment approach for patients. This article aims to comprehensively summarize current academic research hot topics, review the rationale and evaluation measures of neoadjuvant therapy, discuss challenges in restaging methods after neoadjuvant therapy, and identify the advantages and disadvantages of various neoadjuvant therapeutic strategies.

Objective To explore the value of 18F-fluorodeoxyglucose(18F-FDG)PET/CT in predicting the stage of untreated elderly esophageal cancer.Methods The clinical data of 83 esophageal cancer patients who had not received any treatment were ret-rospectively analyzed,including age,body mass index(BMI),lesion length and width,TNM stage,and clinical stage.Spearman correlation analysis was used to evaluate the correlation between TNM stage and clinical stage and the maximum standardized uptake value(SUVmax)of the primary tumor.Linear correlation analysis was used to evaluate the correlation between age,BMI,lesion length and width,and SUVmax.The receiver operating characteristic(ROC)curve of the primary tumor SUVmax in predicting the newly diagnosed elderly esophageal cancer T3-T4 stage and clinical stage Ⅲ-Ⅳ was plotted,the area under the curve(AUC)was obtained,and the best cut off value of the primary tumor SUVmax in the diagnosis of T3-T4 stage and clinical stage Ⅲ-Ⅳ was obtained.Results The T stage and clinical stage were positively correlated with the SUVmax of the primary tumor(r=0.688,P<0.001;r=0.313,P=0.004),while the N stage,M stage,lesion location,age,BMI,lesion length and width were not correlated with the SUVmax(P>0.05).There were significant differences in SUVmax between the T1-T2 stage and the T3-T4 stage,as well as between the clinical stageⅠ-Ⅱ and the Ⅲ-Ⅳ(P<0.05).According to the analysis of ROC curve,the AUC for diagnosing T3-T4 stage and clinical stageⅢ-Ⅳ with the SUVmax of the primary tumor were 0.904[95%confidence interval(CI)0.835-0.973]and 0.700(95%CI 0.570-0.829),respectively,with cut off values of 12.40 and 12.70.The sensitivities were 0.918 and 0.708,respectively,and the specificities were 0.712 and 0.729,respectively.Conclusion 18F-FDG PET/CT primary tumor SUVmax has a good predictive value for the diagnosis of untreated elderly esophageal cancer before treatment of T3-T4 stage and clinical stage Ⅲ-Ⅳ,which can improve the accuracy of esophageal cancer stage.

Objective To observe the effects of needle-knife tendon-sparing and knot-dissolving technique on NF-κB/Bcl-2 pathway activity and the expression of TNF-α,IL-1β,IL-6,Bax and caspase-3 in synovial tissue of knee joints of rabbits with rheumatoid arthritis(RA)model;To explore the mechanism of its inhibitory effect on RA synovial inflammation.Methods Totally 24 New Zealand white rabbits were randomly divided into normal group,model group,drug group and needle-knife group,with 6 rabbits in each group.Except for the normal group,the other groups were injected with ovalbumin and Freund's complete adjuvant into the knee joint cavity to replicate the RA model,and corresponding interventions were given for 18 consecutive days.The knee pain threshold and knee circumference were measured,ultrasound was used to observe the joint cavity effusion,synovial thickness and internal blood flow signals,the synovial tissue morphology were observed by HE staining,the apoptosis of fibroblast-like synoviocytes(FLS)in synovial tissue was observed by TUNEL staining,the expression of TNF-α,IL-1β and IL-6 in synovial tissue were detected by immunohistochemistry,RT-PCR was used to detect NF-κBp65 and Bcl-2 mRNA expression in synovial tissue,Western blot was used to detect the protein expression of NF-κBp65,p-NF-κBp65,Bcl-2,Bax and caspase-3 in synovial tissue.Results Compared with the normal group,the knee pain threshold decreased,knee circumference increased,ultrasonic score and pathological score of synovial tissue increased in the model group;FLS apoptosis rate decreased,the expression of TNF-α,IL-1β and IL-6 in synovial tissue increased,the expressions of NF-κBp65,Bcl-2 mRNA and protein,and p-NF-κBp65 protein increased,while the expression of Bax,caspase-3 protein decreased,with statistical significance(P<0.05).Compared with the model group,the knee pain threshold increased in the drug group and the needle knife group,the circumference of the knee joint decreased,the ultrasonic score and pathological score of synovial tissue were significantly decreased;the apoptosis rate of FLS increased,the expression of TNF-α,IL-1β and IL-6 in synovial tissue decreased,the expressions of NF-κBp65,Bcl-2 mRNA and protein,and p-NF-κBp65 protein decreased,and the expression of Bax and caspase-3 protein increased,with statistical significance(P<0.05).Conclusion Needle-knife tendon-sparing and knot-dissolving technique may promote FLS apoptosis and reduce TNF-α,IL-1β and IL-6 production,inhibit synovial inflammation in RA,reduce knee joint swelling,and raise pain threshold by reducing the activity of synovial tissue NF-κB/Bcl-2 pathway.

Hepatectomy is the most effective method for the treatment of liver cancer. Asso-ciating liver partition and portal vein ligation for staged hepatectomy (ALPPS) provides resectable opportunities for patients with unresectable or borderline resectable liver cancer. Traditional ALPPS procedures involve a short interval between two stages of the surgery, leading to a higher incidence of perioperative complications and mortality. The authors present a case of two-stage hepatectomy. Initially, laparoscopic ligation of the right hepatic artery and portal vein was performed. To prevent tumor progression after the first stage of surgery, combined immunotherapy and targeted therapy were administered. Three months later, a successful right hemihepatectomy was performed. Postoperative histopathological examination revealed hepatocellular carcinoma with extensive tumor necrosis. A 15-month follow-up showed no tumor recurrence. This indicated that two-stage hepatectomy including simultaneous ligation of the hepatic artery and portal vein, combined with two-stage hepatectomy plus immunotherapy and targeted therapy, showed considerable promise for borderline resectable liver cancer.

Sesquiterpenoids are natural compounds composed of 15 carbon atoms， which can be divided into sesquiterpene alcohols， ketones， lactones， aldehydes， and carboxylic acids according to oxygen groups. These compounds are widely distributed in nature， and their physiological activities are diverse. For example， many sesquiterpenes with potential anticancer effects have been found for anti-tumor effects， including cytotoxicity， antioxidant， immune regulation， cell proliferation， and so on. In addition， some sesquiterpenoids have good application prospects in antibacterial， anti-inflammatory， and anti-cardiovascular diseases. Malignant tumors， inflammation， bacterial diseases， and cardiovascular diseases are the main diseases that cause human death， and natural products have unique advantages in the treatment of these diseases. Therefore， the development of new drugs that are easy to promote has become a new research hotspot. In this paper， the sesquiterpenes extracted from the natural components of Chinese herbs and plants with anti-tumor， anti-inflammatory， antibacterial， and anti-cardiovascular activities， such as Xanthium， Atractylodes， Convolvulus， Acanthium， Ligularia， Artemisia， Ligularia， Ligularia， Labiaceae Mint， Acanthophyllum， Turmeria， Ginger， and other Chinese herbs and plants， were discussed. The biological activities and related mechanisms of this compound were reviewed， which provided a reference for further research and clinical application of sesquiterpenes.

Objective To observe the effects of electroacupuncture on intestinal flora and serum inflammatory factors in rabbit model with rheumatoid arthritis(RA);To explore the mechanism of its therapeutic effect on RA.Methods RA model rabbits were established by ovalbumin induction combined with Freund's complete adjuvant,and the rabbits after successful modeling were randomly divided into model group,probiotic group and electroacupuncture group,with 6 rabbits in each group.Another 6 rabbits were set as the normal group.The electroacupuncture group received electroacupuncture at the bilateral"Zusanli"and"Dubi"for 30 minutes,the probiotic group was given probiotic capsules solution(14.5 mg/kg)by gavage,once a day,for two consecutive weeks.The knee joint circumference and pain threshold of rabbits were measured,histopathological morphological changes of colonic tissue and synovial tissue ws observed by HE staining,16S rDNA sequencing was used to analyze structural changes of intestinal flora,the contents of TNF-α,IL-1β and IL-6 in serum were detected by ELISA.Results Compared with the normal group,the circumference of knee joint of rabbits in the model group increased significantly,the pain threshold was significantly decreased(P<0.01);the colonic mucosal damage was serious,the goblet cells were missing,a large number of inflammatory cells were infiltrate;the joint capsule synovial surface was rough,the synovial cell layer was hyperplasia and thickening,the synovial tissue inflammatory cell infiltration was obvious;the number and evenness of gut microbiota species decreased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes decreased(P<0.05,P<0.01),the relative abundance of Desulfobacteria increased(P<0.01),while the relative abundance of Campylobacter,Lawsonella,and Pseudomonas increased(P<0.01),while the relative abundance of Heshanomonas and Herbaspirillum decreased(P<0.01);the contents of serum TNF-α,IL-1β and IL-6 increased(P<0.01).Compared with the model group,the knee joint circumference of the probiotic group and the electroacupuncture group decreased,the pain threshold increased(P<0.01,P<0.05);the degree of intestinal mucosal damage was reduced,the goblet cells were basically arranged neatly,the inflammatory cell infiltration was reduced;synovial cells proliferation and thickening decreased,with a small amount of inflammatory cell infiltration;the number and evenness of gut microbiota species increased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes increased(P<0.05,P<0.01),the relative abundance of Desulfobacteria decreased(P<0.01),while the relative abundance of Campylobacter,Lawsonella and Pseudomonas decreased(P<0.01),the relative abundance of Heshanomonas and Herbaspirillum increased(P<0.05,P<0.01);the contents of serum TNF-α,IL-1β and IL-6 significantly decreased(P<0.01).Conclusion Electroacupuncture can significantly improve the symptoms of RA rabbits and reduce the inflammatory reaction in synovial tissue of joint,and the mechanism may be related to the regulation of intestinal flora structure.

Objective:To analyze the epidemiology, and infant outcomes of congenital diaphragmatic hernia (CDH) in Beijing.Methods:This retrospective study involved cases diagnosed with CDH among 877 230 fetuses/infants monitored by the Beijing Birth Defects Monitoring System from January 2018 to December 2022. Data on the occurrence of CDH, prenatal diagnosis, and infant mortality were analyzed. The statistical method was the Chi-square test (or Fisher's exact test). Results:(1) A total of 254 CDH cases were included in this study. During the study period, the incidence of CDH throughout the pregnancy and the perinatal period was 0.29 per thousand (254/877 230) and 0.17 per thousand (153/877 230), respectively. (2) Among the 254 cases, 79 (31.1%) underwent prenatal genetic diagnosis, 6.3%(5/79) copy number varations were detected, including one case of like pathogenic and four cases with types of variation unreported. The proportions of prenatal genetic diagnosis from 2018 to 2022 showed no statistically significant difference ( χ2trend=2.86, P=0.091). The gestational age at prenatal diagnosis for 241 cases was (23.0±6.4) weeks, ranging from 13 to 38 weeks; 130 cases (53.9%) were diagnosed before 25 weeks of gestation. The proportion of genetic diagnosis was higher in the group diagnosed by ultrasound before 25 weeks (43.1%, 56/130) compared to the group diagnosed at or after 25 weeks (20.7%, 23/111) ( χ2=12.59, P<0.001). (3) A total of 146 live births were recorded, with the proportion of continuing pregnancy to live birth after prenatal diagnosis being 55.2% (133/241), with no significant difference across the years. The proportion of continuing pregnancy to live birth after prenatal diagnosis in the isolated CDH group was 64.5% (100/155), higher than the 38.3% (33/86) in the non-isolated group ( χ2=15.57, P<0.001). The live birth rate for those diagnosed prenatally at<25 weeks of gestation (26.2%, 34/130) was lower than for those diagnosed at≥25 weeks of gestation (89.2%, 99/111) ( χ2=93.67, P<0.001). (4) Among the 146 live-born infants, 28 (19.2%) died during infancy. All 28 cases were prenatally diagnosed with CDH. The mortality rate of CDH infants born in tertiary obstetric institutions (17.9%, 24/134) showed a trend towards being lower than that in secondary institutions (4/12), but the difference was not statistically significant (Fisher's exact test, P=0.245). Among the 118 surviving infants, seven were abandoned from treatment, and of the remaining 111, 104 (93.7%) were treated at the Children's Hospital, Capital Institute of Pediatrics. The infant mortality rate at this institution (15.4%, 16/104) showed a trend towards being lower than that at other institutions (3/7), but the difference was not statistically significant (Fisher's exact test, P=0.096). The infant mortality rate for those diagnosed prenatally at<25 weeks of gestation (38.2%, 13/34) was higher than for those diagnosed at≥25 weeks of gestation (15.2%, 15/99) ( χ2=6.78, P=0.009). Conclusions:Beijing achieved good secondary and tertiary prevention outcomes in prenatal diagnosis and reducing infant mortality. The concentration of neonatal surgical resources is beneficial for accumulating surgical experience and reducing infant mortality.

Objective:To analyze the epidemiology, and infant outcomes of congenital diaphragmatic hernia (CDH) in Beijing.Methods:This retrospective study involved cases diagnosed with CDH among 877 230 fetuses/infants monitored by the Beijing Birth Defects Monitoring System from January 2018 to December 2022. Data on the occurrence of CDH, prenatal diagnosis, and infant mortality were analyzed. The statistical method was the Chi-square test (or Fisher's exact test). Results:(1) A total of 254 CDH cases were included in this study. During the study period, the incidence of CDH throughout the pregnancy and the perinatal period was 0.29 per thousand (254/877 230) and 0.17 per thousand (153/877 230), respectively. (2) Among the 254 cases, 79 (31.1%) underwent prenatal genetic diagnosis, 6.3%(5/79) copy number varations were detected, including one case of like pathogenic and four cases with types of variation unreported. The proportions of prenatal genetic diagnosis from 2018 to 2022 showed no statistically significant difference ( χ2trend=2.86, P=0.091). The gestational age at prenatal diagnosis for 241 cases was (23.0±6.4) weeks, ranging from 13 to 38 weeks; 130 cases (53.9%) were diagnosed before 25 weeks of gestation. The proportion of genetic diagnosis was higher in the group diagnosed by ultrasound before 25 weeks (43.1%, 56/130) compared to the group diagnosed at or after 25 weeks (20.7%, 23/111) ( χ2=12.59, P<0.001). (3) A total of 146 live births were recorded, with the proportion of continuing pregnancy to live birth after prenatal diagnosis being 55.2% (133/241), with no significant difference across the years. The proportion of continuing pregnancy to live birth after prenatal diagnosis in the isolated CDH group was 64.5% (100/155), higher than the 38.3% (33/86) in the non-isolated group ( χ2=15.57, P<0.001). The live birth rate for those diagnosed prenatally at<25 weeks of gestation (26.2%, 34/130) was lower than for those diagnosed at≥25 weeks of gestation (89.2%, 99/111) ( χ2=93.67, P<0.001). (4) Among the 146 live-born infants, 28 (19.2%) died during infancy. All 28 cases were prenatally diagnosed with CDH. The mortality rate of CDH infants born in tertiary obstetric institutions (17.9%, 24/134) showed a trend towards being lower than that in secondary institutions (4/12), but the difference was not statistically significant (Fisher's exact test, P=0.245). Among the 118 surviving infants, seven were abandoned from treatment, and of the remaining 111, 104 (93.7%) were treated at the Children's Hospital, Capital Institute of Pediatrics. The infant mortality rate at this institution (15.4%, 16/104) showed a trend towards being lower than that at other institutions (3/7), but the difference was not statistically significant (Fisher's exact test, P=0.096). The infant mortality rate for those diagnosed prenatally at<25 weeks of gestation (38.2%, 13/34) was higher than for those diagnosed at≥25 weeks of gestation (15.2%, 15/99) ( χ2=6.78, P=0.009). Conclusions:Beijing achieved good secondary and tertiary prevention outcomes in prenatal diagnosis and reducing infant mortality. The concentration of neonatal surgical resources is beneficial for accumulating surgical experience and reducing infant mortality.

There remains a significant gap in our quantitative understanding of crosstalk between apoptosis and necroptosis pathways. By employing the SWATH-MS technique, we quantified absolute amounts of up to thousands of proteins in dynamic assembling/de-assembling of TNF signaling complexes. Combining SWATH-MS-based network modeling and experimental validation, we found that when RIP1 level is below ~1000 molecules/cell (mpc), the cell solely undergoes TRADD-dependent apoptosis. When RIP1 is above ~1000 mpc, pro-caspase-8 and RIP3 are recruited to necrosome respectively with linear and nonlinear dependence on RIP1 amount, which well explains the co-occurrence of apoptosis and necroptosis and the paradoxical observations that RIP1 is required for necroptosis but its increase down-regulates necroptosis. Higher amount of RIP1 (>~46,000 mpc) suppresses apoptosis, leading to necroptosis alone. The relation between RIP1 level and occurrence of necroptosis or total cell death is biphasic. Our study provides a resource for encoding the complexity of TNF signaling and a quantitative picture how distinct dynamic interplay among proteins function as basis sets in signaling complexes, enabling RIP1 to play diverse roles in governing cell fate decisions.
Animals ; Apoptosis ; Caspase 8/metabolism* ; GTPase-Activating Proteins/metabolism* ; HEK293 Cells ; Humans ; Mice ; Mice, Knockout ; Necroptosis ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*