Objective:To explore the effect of complement component C1s on the proliferation,migration and adhesion of esophageal squamous cell carcinoma(ESCC)cells and on the growth of xenograft tumors in nude mice.Methods:The C1S mRNA ex-pression of ESCC tissues and adjacent normal tissues(ANTs)were analyzed using NCBI-GEO database.The C1s expression of ESCC cell lines was analyzed with RT-qPCR and Western blot.The knockdown or overexpression of C1s in ESCC cells lines was performed using C1s small interfering RNA(siRNA),C1s short hairpin RNA(shRNA)or C1s overexpression lentivirus,and the cell prolifera-tion was detected by CCK-8 assay,cell migration was detected by cell wound healing assay,cell adhesion was detected by cell-matrix adhesion assay,the expressions of matrix metalloproteinases MMP1 and MMP13 were detected by Western blot,and the effect of C1s on the growth of xenograft tumors in nude mice was detected by subcutaneous tumorigenesis assay in nude mice.The expression of CD34 in the xenograft tumors was detected by immunohistochemistry,and the formation of tumor microvessel was analyzed.Results:The expression of C1S mRNA in ESCC tissues was significantly higher than that in ANTs.Knockdown of C1s significantly suppressed proliferation,migration and cell-matrix adhesion of ESCC cells,as well as growth of xenograft tumors in nude mice,while overexpres-sion of C1s had the opposite effects.The expressions of MMP1 and MMP13 were decreased in ESCC cells TE-1 with C1s knockdown.Compared with control group,the microvessel of the xenograft tumors in the C1s overexpression group were more abundant.Conclu-sion:C1s is significantly upregulated in ESCC tissues,and promotes proliferation,migration,cell-matrix adhesion of ESCC cells,and the growth of xenograft tumors.C1s may play an important role in the occurrence and development of ESCC.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

BACKGROUND: Lung cancer prevails and induces high mortality around the world. This study provided real-world information on the evolution of clinicopathological profiles and survival outcomes of lung cancer, and provided survival information within stage I subtypes. METHODS: Patients pathologically confirmed with lung cancer between January 2009 and December 2018 were identified with complete clinicopathological information, molecular testing results, and follow-up data. Shifts in clinical characteristics were evaluated using χ2 tests. Overall survival (OS) was calculated through the Kaplan-Meier method. RESULTS: A total of 26,226 eligible lung cancer patients were included, among whom 62.55% were male and 52.89% were smokers. Non-smokers and elderly patients took increasingly larger proportions in the whole patient population. The proportion of adenocarcinoma increased from 51.63% to 71.80%, while that of squamous carcinoma decreased from 28.43% to 17.60%. Gene mutations including EGFR (52.14%), KRAS (12.14%), and ALK (8.12%) were observed. Female, younger, non-smoking, adenocarcinoma patients and those with mutated EGFR had better survival prognoses. Importantly, this study validated that early detection of early-stage lung cancer patients had contributed to pronounced survival benefits during the decade. Patients with stage I lung cancer, accounted for an increasingly considerable proportion, increasing from 15.28% to 40.25%, coinciding with the surgery rate increasing from 38.14% to 54.25%. Overall, period survival analyses found that 42.69% of patients survived 5 years, and stage I patients had a 5-year OS of 84.20%. Compared with that in 2009-2013, the prognosis of stage I patients in 2014-2018 was dramatically better, with 5-year OS increasing from 73.26% to 87.68%. Regarding the specific survival benefits among stage I patients, the 5-year survival rates were 95.28%, 93.25%, 82.08%, and 74.50% for stage IA1, IA2, IA3, and IB, respectively, far more promising than previous reports. CONCLUSIONS Crucial clinical and pathological changes have been observed in the past decade. Notably, the increased incidence of stage I lung cancer coincided with an improved prognosis, indicating actual benefits of early detection and management of lung cancer.
Humans ; Male ; Female ; Aged ; Lung Neoplasms/genetics* ; Adenocarcinoma/pathology* ; Prognosis ; Survival Rate ; Mutation ; ErbB Receptors/genetics* ; Neoplasm Staging ; Retrospective Studies

As confusion mounts over RNA isoforms involved in phenotypic plasticity, aberrant CpG methylation-mediated disruption of alternative splicing is increasingly recognized as a driver of intratumor heterogeneity (ITH). Protease serine 3 (PRSS3), possessing four splice variants (PRSS3-SVs; PRSS3-V1-V4), is an indispensable trypsin that shows paradoxical effects on cancer development. Here, we found that PRSS3 transcripts and their isoforms were divergently expressed in lung cancer, exhibiting opposing functions and clinical outcomes, namely, oncogenic PRSS3-V1 and PRSS3-V2 versus tumor-suppressive PRSS3-V3, by targeting different downstream genes. We identified an intragenic CpG island (iCpGI) in PRSS3. Hypermethylation of iCpGI was mediated by UHRF1/DNMT1 complex interference with the binding of myeloid zinc finger 1 (MZF1) to regulate PRSS3 transcription. The garlic-derived compound diallyl trisulfide cooperated with 5-aza-2'-deoxycytidine to exert antitumor effects in lung adenocarcinoma cells through site-specific iCpGI demethylation specifically allowing MZF1 to upregulate PRSS3-V3 expression. Epigenetic silencing of PRSS3-V3 via iCpGI methylation (iCpGIm) in BALF and tumor tissues was associated with early clinical progression in patients with lung cancer but not in those with squamous cell carcinoma or inflammatory disease. Thus, UHRF1/DNMT1-MZF1 axis-modulated site-specific iCpGIm regulates divergent expression of PRSS3-SVs, conferring nongenetic functional ITH, with implications for early detection of lung cancer and targeted therapies.

The review summarizes the kidney protective mechanism of sodium-glucose-coupled transporter 2 inhibitors and their efficacy and safety for diabetic recipients of kidney transplantation.It is intended to improve patient outcomes.

Based on the limitations of certain conditions in the traditional clinical pathology teaching, this paper puts forward the "quaternity" hybrid digital teaching reform practice of clinical medicine, imaging, anatomy and pathology content. This teaching method can optimize the teaching process and improve the teaching efficiency. The specific advantages of this teaching method are as follows: the digital materials of different modules of clinical practice, imaging, anatomy and pathology are integrated to make the teaching content more perfect; it is helpful to improve the cognition of resident doctors on the pathological characteristics and the overall characteristics of the disease, and promote their thinking ability of clinicopathological integration; the combination of hybrid digital teaching and various teaching methods, including clinical pathology discussion, makes teaching more free and is conducive to classroom learning and self-learning. This paper discussed the construction and application of the "quaternity " hybrid digital teaching mode, and provided new ideas and methods for clinical pathology teaching and talent training.

Cell Cycle Proteins ; Microtubule-Associated Proteins

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.

Objective:To investigate the effects of cyclic tensile stress on the function and degeneration of nucleus pulposus cells.Methods:The human primary nucleus pulposus cells were isolated and cultured. The cyclic tensile stress (100 000 μ?, 10% tensile strain, 0.1 Hz, 8 640 cycles) was loaded on the cells for 24 h. The proliferation of the cells was examined by MTT method. The cell cycle and apoptosis were detected through flow cytometry. Gene expression profile chip was used to detect the differentially expressed genes between the tensile stress group and control group. The function of these gene was analyzed by bioinformatics. The expression of inflammatory related factors, TGF-β, matrix degrading enzymes and extracellular matrix molecules were examined by qRT-PCR.Results:The cyclic tensile stress significantly promoted proliferation and cell cycle of nucleus pulposus cells. The cell percentage of S phase ( t=5.336, P<0.05) and G2/M phase ( t=7.288, P<0.01) was significantly different between the tensile stress group and control group. The cyclic tensile stress inhibited apoptosis of nucleus pulposus cells (8.56%±0.48% vs 10.63%±0.32%, t=4.474, P<0.05). A total of 866 differentially expressed genes were detected. Gene ontology analysis showed the roles of these genes in cells including focal adhesion, extractable matrix, membrane raft, condensed chrome kinetochore, cytoskeleton, etc. The cyclic tensile stress significantly affected the mRNA expression of inflammatory related factors, TGF-β genes, matrix proteinase and extracellular matrix molecules. Compared with the control group, the mRNA expression of inflammatory related factors IL15 ( t=5.379, P<0.05), IGF1 ( t=5.454, P<0.05) and IGFBP7 ( t=13.57, P<0.01) were significantly decreased in the tensile stress group; The mRNA expression of TGF-β genes TGFB1 ( t=6.931, P<0.05), TGFB2 ( t= 15.56, P<0.01) and TGFB3 ( t=7.744, P<0.05) were significantly increased in the tensile stress group; The mRNA expression of matrix proteinase ADAMTS3 ( t=5.241, P<0.05) and MMP19 ( t=24.72, P<0.01) were significantly decreased, and TIMP3 ( t=8.472, P<0.01) increased in the tensile stress group; The mRNA expression of extracellular matrix molecules COL2A1 ( t=5.871, P<0.05), FLRT2 ( t=5.216, P<0.05) and FN1 ( t=4.289, P<0.05) were significantly increased. Conclusion:The cyclic tensile stress promoted cell cycle and proliferation and inhibited apoptosis of nucleus pulposus cells. The cyclic tensile stress may affect the function and degeneration of nucleus pulposus cells by regulating the expression of inflammatory related factors, TGF-β, matrix degradation enzymes and ECM molecules.

Objective To investigate the value of DWI in the evaluation of the therapeutic effect of cyber knife in the treatment of hepatocellular carcinoma.Methods Ninety patients who were clinically diagnosed with hepatocellular carcinoma (95 lesions) in the 5th Medical Center of General Hospital of PLA from February 2011 to December 2013 were retrospectively analyzed. All 90 patients underwent pre‐treatment dynamic contrast‐enhanced MRI scans of liver. Fourty six of them underwent liver MRI scan 3 months after treatment with cyber knife, and 49 patients underwent liver MRI scans 6 months after treatment. According to the evaluation criteria of solid tumor effect, complete necrosis tumor lesions and postoperative residual active lesions were determined. The ADC values of residual active tissue lesion, necrosis lesion in tumor and normal liver were measured. Paired sample t test was used to compare the difference of ADC values of tumor necrosis lesions and normal liver tissues between 3 and 6 months after treatment and before treatment, and ROC was used to evaluate the efficacy of ADC values in predicting complete tissue necrosis after treatment. Results In the 95 lesions, 91 lesions were completely necrotic, and active tissues were found in 4 lesions after treatment. There were statistically significant differences in the ADC values of the lesions at 3 and 6 months after treatment and before treatment (P<0.05),and the ADC values of the tissues after treatment were higher than those before treatment. There was no statistically significant difference in ADC values between 3 and 6 months after treatment and before treatment in normal liver tissue (P>0.05). The area under the ROC of using ADC value to predict the complete necrosis after treatment with cyber knife was 0.767, and the ADC value was 1.23×10‐3 mm2/s as the diagnostic cutoff value. The sensitivity and specificity of the diagnosis were 76.5% and 70.6%, respectively. Conclusion ADC values can distinguish the necrotic component from the active component of hepatocellular carcinoma after treatment, and can be used to evaluate the therapeutic effect of cyber knife in hepatocellular carcinoma.