Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

AIM: To investigate the effect of intravitreal injection of recombinant tissue plasminogen activator(r-TPA)before pars plana vitrectomy(PPV)on surgical outcomes in patients with rupture of the globe(RG).METHODS: A retrospective study was conducted on 37 patients(37 eyes)with RG who underwent PPV 7-10 d after Stage Ⅰ suturing and stabilization at our hospital between April 2020 and November 2023. Based on whether an intravitreal r-TPA injection was administered 1 d before PPV, patients were divided into two groups, with 14 cases(14 eyes)in pre-operative r-TPA injection group, and 23 cases(23 eyes)in control group without pre-operative r-TPA injection. The intraoperative retinal reattachment rate, intraoperative silicone oil application, postoperative intraocular rebleeding, postoperative hypotony, and best-corrected visual acuity(BCVA)were compared between the two groups.RESULTS: The baseline characteristics were comparable between the two groups(P>0.05). Significant differences were found between the two groups in the intraoperative retinal reattachment rate, the volume of silicone oil injected, and the proportion of BCVA(all P<0.05). No statistically significant differences were observed in the intraoperative silicone oil tamponade rate, postoperative intraocular rebleeding, or postoperative hypotony rates(all P>0.05).CONCLUSION: RG patients who received an intravitreal r-TPA injection 1 d before PPV demonstrated significantly higher intraoperative retinal reattachment rates and better postoperative visual acuity outcomes.

Objective To explore the mechanism of immediate effect regulated by acupuncture on acupoints in patients with migraine without aura(MwoA)during the interictal period.Methods A total of 28 MwoA patients were enrolled and resting-state functional magnetic resonance imaging(rs-fMRI)were performed at baseline and after acupuncture for 30 minutes.Paired t test was used to compare the differences of regional homogeneity(ReHo)and voxel-mirrored homotopic connectivity(VMHC)between two groups.Additionally,the correlation between the changes of rs-fMRI indexes and clinical scores was analyzed.Results In MwoA patients after acupuncture for 30 minutes,the mean regional homogeneity(mReHo)was decreased in the right lingual gyrus and right cere-bellum and was increased in the right middle frontal gyrus,while the z transformation voxel-mirrored homotopic connectivity(zVMHC)was significantly decreased in the bilateral cuneus compared with baseline.There was no significant correlation between imaging data and clinical scales.Conclusion Patients with MwoA after acupuncture for 30 minutes show abnormal ReHo and VMHC in multiple brain regions,which suggest that the mechanism of immediate effect may act through regulating pain-related brain regions.

Recently,adeno-associated virus(AAV)vectors have been a hotspot in gene therapy and have shown great potential for rare diseases therapy,due to their low pathogenicity,mild immunogenicity and high tissue specificity.The safety and efficacy of AAV vectors,which are essentially infectious viruses,require new bioanalytical techniques to assess.At present,the relevant industry guidelines have specified the needs for the assessment of biodistribution,shedding,and immunogenicity,but the requirements related to bioassay are limited.In this paper,we reviewed the bioanalytical techniques and pharmacokinetics/pharmacodynamics(PK/PD)research of AAV vectors and their challenges from four aspects:biodistribution,shedding,immunogenicity and PK/PD research,with the hope of providing some reference for the clinical development of AAV vectors gene therapy products.

Objective:To investigate the synergistic effect of physical intervention and chemotherapeutic drug therapy on tumor growth by blocking tumor microvessels and injecting chemotherapy drug Endostar (ecombinant human vascular endostatin injection) to inhibit tumor neovascularization by low intensity ultrasound induced microbubble cavitation combined with hemocoagulase.Methods:Seventy-five male NU/NU mice bearing human-derived lung adenocarcinoma, weighing 25-30 g, were randomly divided into microbubble-enhanced ultrasonic cavitation+ Endostar group (MEUC+ Endostar), microbubble-enhanced ultrasonic cavitation+ hemocoagulase+ Endostar group (MEUC+ HC+ Endostar), microbubble-enhanced ultrasonic cavitation (MEUC), Endostar group (Endostar) and sham group. Fifteen mice in each group were given the corresponding treatment intervention for 4 consecutive days followed by 4 days of aseptic feeding. Two-dimensional ultrasound and contrast-enhanced ultrasound (CEUS) were performed before intervention, immediately after intervention and 4 days after intervention, respectively. Tumor tissues were obtained for vascular endothelial growth factor immunofluorescence staining, and microvessel density (MVD) was observed.Results:There was no difference in tumor volume between the groups before the intervention ( P>0.05). Immediately after the intervention, filling defects were observed in MEUC+ Endostar group, MEUC+ HC+ Endostar group and MEUC group, while filling was good in Endostar group and sham group; 4 days after the intervention, filling defects were observed in MEUC+ Endostar group and MEUC+ HC+ Endostar group. The filling defect was still present in Endostar group, while partial recovery of perfusion was performed in MEUC group, and PI and AUC were still significantly lower in MEUC+ HC+ Endostar group than in the other groups ( P<0.05). When tumor tissues were obtained 4 days after the intervention, the MVD in MEUC+ HC+ Endostar group was significantly lower than that in the remaining groups, and the difference of MVD in tumor tissue was statistically significant ( P<0.05). Conclusions:Low intensity ultrasound induced microbubble cavitation combined with hemocoagulase and Endostar can produce a synergistic effect in blocking tumor microvessels and inhibiting tumor angiogenesis, which can more effectively inhibit tumor growth.

Objective:To explore the medication rules of Professor Wang Pei in the treatment of colon cancer.Methods:The medical records of Professor Wang Pei's outpatient treatment for colon cancer were collected, entered into the Traditional Chinese Medicine Inheritance Computing Platform V3.0, and the laws of the prescription's nature, flavor, meridian, drug frequency, drug combination, association rules, and cluster analysis were explored.Results:A total of 65 prescriptions were collected, including 150 Chinese materia medica. The medicinal properties of these Chinese materia medica are mainly warm, cold and flat, the tastes were mainly sweet, bitter and pungent, and the meridians were mainly liver, spleen and kidney meridians. Dampness category and blood circulation promoting and blood stasis category were mainly used, and the most frequently used drugs include Poria, Polyporus, Scutellariae Barbatae Herba, Astragali Radix, Curcumae Rhizoma, and the pairs of Polyporus- Poria, Astragali Radix- Astragali Radix Praeparata cum Melle, Scutellariae Barbatae Herba- Curcumae Rhizoma. Twenty nine high-related drug pairs were obtained from association rules, including Polyporus- Astragali Radix Praeparata cum Melle- Astragali Radix, Poria- Scutellariae Barbatae Herba- Polyporus, Scutellariae Barbatae Herba- Curcumae Rhizoma- Polyporus. The cluster analysis showed the combination of 6 types of medicines mainly focuses on strengthening the spleen and removing dampness, nourishing qi and promoting blood, clearing heat and detoxifying, and astringing the intestines to stop bleeding. Conclusion:Professor Wang Pei mostly discusses the treatment of colon cancer from "spleen dampness, rectification deficiency, heat toxin, blood stasis, bleeding", and the treatment is "invigorating the spleen and removing dampness, invigorating Qi and strengthening the body, clearing away heat and detoxifying, promoting blood circulation and removing blood stasis, and astringent intestines to stop bleeding", which is in line with the thought of Traditional Chinese Medicine treatment of tumors, strengthening the righteousness and eliminating pathogenic factors, and and can be used for clinical reference.

Objective:To improve the understanding of chronic lymphoblastic leukemia (CLL) with t(14;18)(q32;q21).Methods:The clinical data of 3 cases diagnosed as CLL with t(14;18)(q32;q21) in the Tianjin KingMed Medical Laboratory from January 2020 to January 2021 were retrospectively analyzed. The clinicopathological data, morphological examination, immunophenotype, cytogenetics and somatic mutation of immunoglobulin heavy chain variable region genes of patients were comprehensively analyzed, and the literature was reviewed.Results:All the 3 patients showed lymphatic proliferative diseases, and their morphological characteristics and immunophenotype were typical characteristics of CLL.Conclusions:The diagnosis of CLL is mainly based on the typical morphology and immunophenotype of tumor cells. The presence of t(14;18) should not be used to exclude the diagnosis of CLL.

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

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*

Red, white, blue, green, and yellow lights were applied to investigate their effects on folate accumulation in wheat seedlings. The different lights, especially red light, significantly increased the total folate content. Total folate showed maximum accumulation under 30 μmol/(m