Objective To investigate the expression level of centromere protein(CENP)Ⅰin lung adenocarcinoma cells,to study the effects of CENPⅠon the proliferation,invasion,migration,apoptosis,and epithelial-mesenchymal transition(EMT)of lung adenocarci-noma cells,and to explore the possible mechanisms related to its occurrence.Methods The expression of CENPⅠmRNA and protein in four types of lung adenocarcinoma cells and normal alveolar epithelial cells were detected by quantitative real-time polymerase chain reaction(RT-qPCR)and Western blotting.The expression of CENPⅠin H1650 cells was knocked down by the siRNA technique,The transfection efficiency was detected by RT-qPCR and Western blotting.The effects of knock-down CENPⅠon proliferation,cell cycle,apoptosis,invasion and migration of H1650 cells were detected by the cell counting kit-8 assay,the transwell assay,and flow cytometry.Western blotting was used to detect the expression of E-cadherin,N-cadherin,vimentin,Ki-67,cyclin D1,Bcl-2,PI3K,AKT,mTOR,p-PI3K,p-AKT,and p-mTOR.Results After the knock-down of CENPⅠ,the proliferative ability of the H1650 cells significantly decreased,the number of apoptotic cells significantly decreased,and the cell invasion and migration abilities significantly decreased(P<0.01).E-cadherin expression was upregulated and N-cadherin,vimentin,Ki-67,cyclin D1,Bcl-2,p-PI3K,p-AKT,and p-mTOR expres-sion were down-regulated in the CENTI group compared with the control group(P<0.05).The expression of p-PI3K,p-AKT,and p-mTOR in the si-CENPⅠ+IGF-1 group was upregulated compared to that in the si-CENPⅠgroup(P<0.05).Conclusion High expression of CENPⅠin lung adenocarcinoma cells promotes the proliferation,invasion,and migration of lung adenocarcinoma H1650 cells and EMT inhibits apoptosis,which may be related to the activation of the PI3K/AKT/mTOR signaling pathway.

Rare diseases pose significant diagnostic and therapeutic challenges,carrying a high disease burden,their management critically reflects a nation's public health resilience.Currently,China faces key challenges such as scarce treatments,fragmented services,and low drug accessibility in rare disease care,which urgently require systemic solutions.Digital-intelligent technology as a key breakthrough are expected to resolve the challenges in this field.Although its application in the field of rare diseases is gradually expanding,there is a lack of systematic compilation of studies to elucidate how to precisely enhance the precision,synergy and sustainability of diagnosis and treatment.The key challenges in rare disease care concentrate in four areas:inefficiency in prenatal screening,uneven distribution of medical resources,low efficiency in social organization collaboration,and ineffective information dissemination.The"4C"strategy,based on digital-intelligent technology,can address these issues:①coordination,boost prenatal screening awareness and capacity via digital-intelligent platforms to strengthen prevention;②cooperation,deepen collaboration within specialist networks,empowering institutions to enhance diagnostic capacity;③co-creation,empower support organizations to optimize resources,efficiency;④cognition,minimize information dissipation through efficient platforms,improving patient and family quality of life.This establishes an integrated digital-intelligent rare disease model encompassing"screening-diagnosis-treatment-care".

Objective To investigate the expression level of centromere protein(CENP)Ⅰin lung adenocarcinoma cells,to study the effects of CENPⅠon the proliferation,invasion,migration,apoptosis,and epithelial-mesenchymal transition(EMT)of lung adenocarci-noma cells,and to explore the possible mechanisms related to its occurrence.Methods The expression of CENPⅠmRNA and protein in four types of lung adenocarcinoma cells and normal alveolar epithelial cells were detected by quantitative real-time polymerase chain reaction(RT-qPCR)and Western blotting.The expression of CENPⅠin H1650 cells was knocked down by the siRNA technique,The transfection efficiency was detected by RT-qPCR and Western blotting.The effects of knock-down CENPⅠon proliferation,cell cycle,apoptosis,invasion and migration of H1650 cells were detected by the cell counting kit-8 assay,the transwell assay,and flow cytometry.Western blotting was used to detect the expression of E-cadherin,N-cadherin,vimentin,Ki-67,cyclin D1,Bcl-2,PI3K,AKT,mTOR,p-PI3K,p-AKT,and p-mTOR.Results After the knock-down of CENPⅠ,the proliferative ability of the H1650 cells significantly decreased,the number of apoptotic cells significantly decreased,and the cell invasion and migration abilities significantly decreased(P<0.01).E-cadherin expression was upregulated and N-cadherin,vimentin,Ki-67,cyclin D1,Bcl-2,p-PI3K,p-AKT,and p-mTOR expres-sion were down-regulated in the CENTI group compared with the control group(P<0.05).The expression of p-PI3K,p-AKT,and p-mTOR in the si-CENPⅠ+IGF-1 group was upregulated compared to that in the si-CENPⅠgroup(P<0.05).Conclusion High expression of CENPⅠin lung adenocarcinoma cells promotes the proliferation,invasion,and migration of lung adenocarcinoma H1650 cells and EMT inhibits apoptosis,which may be related to the activation of the PI3K/AKT/mTOR signaling pathway.

Rare diseases pose significant diagnostic and therapeutic challenges,carrying a high disease burden,their management critically reflects a nation's public health resilience.Currently,China faces key challenges such as scarce treatments,fragmented services,and low drug accessibility in rare disease care,which urgently require systemic solutions.Digital-intelligent technology as a key breakthrough are expected to resolve the challenges in this field.Although its application in the field of rare diseases is gradually expanding,there is a lack of systematic compilation of studies to elucidate how to precisely enhance the precision,synergy and sustainability of diagnosis and treatment.The key challenges in rare disease care concentrate in four areas:inefficiency in prenatal screening,uneven distribution of medical resources,low efficiency in social organization collaboration,and ineffective information dissemination.The"4C"strategy,based on digital-intelligent technology,can address these issues:①coordination,boost prenatal screening awareness and capacity via digital-intelligent platforms to strengthen prevention;②cooperation,deepen collaboration within specialist networks,empowering institutions to enhance diagnostic capacity;③co-creation,empower support organizations to optimize resources,efficiency;④cognition,minimize information dissipation through efficient platforms,improving patient and family quality of life.This establishes an integrated digital-intelligent rare disease model encompassing"screening-diagnosis-treatment-care".

Objective:To investigate the effects of improving the prenatal multidisciplinary consultation mode on the outcomes of fetuses with structural malformations.Methods:Clinical data of pregnant women attending the Prenatal Multidisciplinary Consultation Center, jointly established by the Obstetrics & Gynecology Hospital of Fudan University and the Children's Hospital of Fudan University from January 2004 to December 2019, were retrospectively collected and analyzed. In 2014, the center optimized the multidisciplinary consultation mode to achieve a more individualized approach to genetic testing based on more accurate imaging diagnosis and deeper cooperation between the obstetrics and pediatrics teams. Differences in the number of cases, structure of the diseases, genetic testing results, outcomes, and prognosis between the improved group (enrolled from January 2014 to December 2019) and the baseline group (enrolled from January 2004 to December 2013) were compared. The Chi-square test was used for statistical analysis. Results:(1) This study recruited 5 977 pregnant women, including 3 424 in the baseline group and 2 553 in the improved group. The main indications for consultation were fetal factors [97.2% (5 812/5 977)], among which congenital structural malformations accounted for 77.5% (4 503/5 812). There was a significant difference in the systematic distribution of congenital structural malformations between the two groups ( χ2=141.31, P<0.001). The proportion of malformations involving the central nervous, cardiovascular, and urinary systems ranked in the top three in both groups. (2) The percentage of women receiving genetic testing was higher in the improved group than in the baseline group [26.7% (682/2 553) vs. 15.9% (546/3 424), χ2=103.87, P<0.001] and the positive rate of genetic testing was also higher in the improved group [19.9% (136/682) vs. 9.9% (54/546). χ2=23.42, P<0.001]. (3) Among the 5 977 cases, 418 (7.0%) were lost to follow-up; 1 741 (29.1%) opted for pregnancy termination; 123 (2.2%) had intrauterine fetal death; and 3 695 (61.8%) were live births. The rate of pregnancy termination in the improved group was lower than that of the baseline group [27.7% (707/2 553) vs. 30.2% (1 034/3 424), χ2=4.45, P=0.035]. (4) In the 1 741 cases with pregnancy termination, fatal cardiovascular system malformations ( n=413, 23.7%), central nervous system malformations ( n=377, 21.7%), multiple malformations ( n=258, 14.8%), and chromosomal abnormalities ( n=162, 9.3%) were the main causes. The top five diseases leading to pregnancy termination were cleft lip and palate [59.0% (46/78)], meningocele (5/9), gastroschisis/omphalocele [49.3% (33/67)], diaphragmatic hernia [46.5% (33/71)], and skeletal malformations [40.9% (83/203)]. The rates of pregnancy termination due to gastroschisis/omphalocele, diaphragmatic hernia, and skeletal malformations in the improved group were all lower than those in the baseline group [57.4% (27/47) vs. 30.0% (6/20), χ2=4.23; 59.0% (23/39) vs. 31.3% (10/32), χ2=5.43; 51.8% (72/139) vs. 17.2% (11/64), χ2=21.72; all P<0.05]. (5) Among the 3 695 live births, 1 979 (53.6%) were delivered by cesarean section and 1 716 (46.4%) by vaginal delivery; 3 633 (98.3%) survived and 62 (1.7%) died in the neonatal period. The survival rate of newborns in the improved group was higher than that in the baseline group [98.8% (1 648/1 668) vs. 97.9% (1 985/2 027), χ2=4.23, P=0.040]. Among the 62 dead newborns, 51 (82.3%) had fatal structural or chromosomal abnormalities. (6) In the surviving neonates, 372 (10.2%) showed no abnormalities in a postnatal reexamination, and 468 (12.9%) received surgical treatment in the neonatal period. The other 2 793 cases received no treatment in the neonatal period but were followed up regularly. Conclusion:The optimized prenatal multidisciplinary consultation mode effectively reduces the rate of pregnancy termination due to non-fatal single structural malformations and increases the survival rate of newborns.

Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.
Humans ; Epigenesis, Genetic ; Gastric Mucosa/metabolism* ; Chromatin/metabolism* ; Stem Cells ; Epithelium/metabolism* ; Fatty Acid-Binding Proteins/metabolism*

Objective:To investigate the occurrence and influencing factors of perioperative complications after robotic gynecologic surgery.Methods:The clinical data and occurrence of perioperative complications in 1 000 cases robotic surgery completed in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed.Results:(1) Clinical data: the average age of the patients was (50.2±10.4) years old, and the average body mass index (BMI) was (24.4±3.6) kg/m 2. Among 1 000 cases, 811 cases of them were malignant tumors, including 405 cases of cervical cancer, 279 cases of endometrial carcinoma, 112 cases of epithelial ovarian cancer (EOC), 15 cases of vulvar cancer; 189 cases of them were benign diseases, including 43 cases of uterine prolapse, 57 cases hysterectomy of uterine leiomyoma and adenomyosis of the uterus ≥12 weeks, 84 cases myomectomy of uterine leiomyoma, and 5 cases of fallopian tubal ligation requiring anastomosis. Surgical methods: in patients with malignant tumors, cervical cancer, hysterectomy plus salpingectomy or salpingo-oophorectomy for stage Ⅰa1, and radical hysterectomy plus pelvic lymphatic dissection plus salpingectomy or salpingo-oophorectomy for stage Ⅰa2-Ⅱb. Endometrial carcinoma, performed by staging surgery. Staging surgery for EOC with early stage and cytoreductive surgery with advanced EOC. Vulvar cancer, extensive vulvar resection plus inguinal lymphadenectomy. In patients with benign diseases, uterine prolapse, hysterectomy plus salpingectomy or salpingo-oophorectomy plus sacrocolpopexy. Uterine leiomyoma or adenomyosis with uterus ≥ 12 weeks, hysterectomy plus salpingectomy or salpingo-oophorectomy. Myomectomy for patients requiring uterine preservation with uterine leiomyoma. Tubal anastomosis for patients with fallopian tubal ligation. (2) Surgical complications: intraoperative complications occurred in 25 patients (2.5%, 25/1 000), including 11 patients with vascular laceration, 11 patients with ureteral injury, 2 patients with bladder injury, and 1 patient with intestinal injury. Postoperative complications occurred in 130 patients (13.0%, 130/1 000), including 66 cases of lower limb venous thrombosis, 20 cases of lymphatic cyst, 8 cases of hydronephrosis, 9 cases of ileus, 16 cases with infection, 6 cases with genital fistula, 4 cases with trocar site herniation and 1 case with subcutaneous emphysema. The incidence of intraoperative complications was 3.1% (25/811) in malignant tumors and no case in benign diseases, the incidence rate in malignant tumors was significantly higher than that in benign diseases ( χ2=4.778, P=0.029). The incidence rate in cervical cancer (4.2%, 17/405) and EOC (3.6%, 4/112) were significantly higher than those in endometrial carcinoma (1.4%, 4/279) and vulvar cancer (0/15; P<0.05). The incidence of postoperative complications was 15.2% (123/811) in malignant tumors and 3.7% (7/189) in benign diseases. The incidence rate in malignant tumors was significantly higher than that in benign diseases ( χ2=17.807, P<0.01), but there were no significant difference among different malignant tumors ( χ2=4.318, P=0.229). (3) The correlative factors affecting the occurrence of surgical complications: patient′s age, BMI, previous pelvic or abdominal surgery history, the nature of disease (malignant or benign), operation time, and comorbidities had a significant impact on the incidence of postoperative complications ( P<0.05). Multivariate logistic regression analysis showed that the patient′s age ≥40 years old, BMI ≥25 kg/m 2, previous pelvic or abdominal surgery history, malignant tumors and comorbidities were independent influential factors of the postoperative complications ( P<0.05). Conclusions:Perioperative complications vary according to the type of the surgery. The age, BMI, previous pelvic or abdominal surgery history, malignant tumors, and comorbidities are influential factors of postoperative complications.

Objective:To observe the outcome of posterior staphyloma (PS) marginal retinal photocoagulation in pars plana vitrectomy (PPV) for high myopia macular hole retinal detachment eyes accompanied with PS.Methods:From January 2017 to June 2019, 49 patients (49 eyes) with high myopia macular hole retinal detachment accompanied with PS who were undergone PPV operation from Tianjin Eye Hospital were included in this study. There were 13 males (13 eyes) and 36 females (36 eyes). All patients underwent best corrected visual acuities (BCVA) and optical coherence tomography examinations. The standard logarithmic visual acuity chart was used for BCVA examination, and the visual acuity was converted to minimum resolution angle in logarithmic (logMAR) when recorded. The patients were randomly divided into two groups according to surgical options: conventional PPV with internal limiting membrane (ILM) peeling (group A, 24 eyes), PS marginal retinal photocoagulation in PPV with ILM peeling (group A, 25 eyes). The mean preoperative logMAR BCVA of group A and B were 1.87±0.28 and 1.80±0.37, the difference was not statistically significant ( t=0.604, P=0.551). The patients in the group A received 23G PPV, triamcinolone acetonide staining during the operation, the epiretinal membrane was peeled off, indocyanine green assisted staining, the posterior macular ILM was peeled off, and the peripheral retina was examined in detail during the operation. Areas with retinal degeneration were reinforced by laser photocoagulation, and the subretinal fluid was drained through the macular hole and filled with silicone oil. The eyes of the group B were subjected to retinal photocoagulation for 2 to 3 rows at the edge of the PS in addition to the usual surgical procedures. The average follow-up time was 8.34±3.21 months. Surgical outcome were estimated by the average number of operation, retinal reattachment rate, macular hole closure rate and BCVA. The χ2 test or Fisher exact probability was used to compare the count data. Independent sample t test was used to compare the measurement data. Results:Retinal reattachment was obtained in 17 eyes (70.8%, 17/24) and 24 eyes (96.0%, 24/25) in group A and B after first surgery respectively, the difference was statistically significant ( χ2=3.984, P=0.046). Final retinal reattachment was obtained in all 49 eyes. Final macular hole closure was in 15 eyes (62.5%, 15/24) and 19 eyes (76.0%, 19/25) in group A and B, respectively, the difference was not statistically significant ( χ2=1.051, P=0.305). The mean postoperative logMAR BCVA of group A (1.20±0.47) and B (1.08±0.39) were all improved than preoperative BCVA, the differences were all statistically significant ( t=2.899, 5.327; P=0.001, 0.000), the differences of mean postoperative logMAR BCVA between two groups was not statistically significant ( t=0.675, P=0.506). The mean number of operation of group A (2.63±0.88) was more than group B (2.08±0.28), the difference was statistically significant ( t=3.003, P=0.006). Conclusion:In comparison with conventional PPV, combined PS marginal retinal photocoagulation can improve retinal reattachment rate after first surgery, and reduce the number of reoperations.

Objective:To observe the changes of macular microvessels in patients with retinal vein occlusion (RVO) and macular edema (ME) after intravitreal injection of aflibercept (IVA), and analyze its correlation with best corrected visual acuity (BCVA).Methods:A retrospective case study. Thirty patients (30 eyes) with monocular RVO with ME (RVO-ME) who were diagnosed in the clinical examination of Tianjin Eye Hospital from April 2019 to February 2020 were included in the study. Among them, there were 12 males (12 eyes) and 18 females(18 eyes); the average age was 54.30±13.17 years. The average course of disease was3.43±1.97 months. Both eyes were examined by BCVA and optical coherence tomography (OCTA). The on-demand injection was adopted after the first injection in IVA treatment regimen. The macular area 6 mm×6 mm in both eyes was scanned with an OCTA instrument, and the area of the foveal avascular area (FAZ), FAZ circumference (PERIM), and out-of-roundness were measured at baseline and 1, 3, and 6 months after treatment. Index (AI), blood flow density within 300 μm width of FAZ (FD-300), foveal retinal thickness (CMT), superficial retinal capillary plexus (SCP), deep retinal capillary plexus (DCP) blood flow density. The paired t test was used to compare the quantitative parameters of the affected eye and the contralateral healthy eye at baseline; the changes of the quantitative parameters at baseline and 1, 3, and 6 months after treatment were analyzed by repeated measures analysis of variance. Pearson correlation analysis was used to analyze the correlation between BCVA, retinal perfusion, and macular blood supply parameters at 6 months after IVA treatment. Results:At baseline, compared with the contralateral healthy eye, the FAZ area ( t=-4.091), PERIM ( t=-5.098) and AI ( t=-9.093) of the RVO-ME eye were enlarged, and FD-300 ( t=7.237) and overall SCP and DCP blood flow density ( t=8.735, 9.897) decreased, the difference was statistically significant ( P<0.001). Six months after treatment, the BCVA of RVO-ME eyes was significantly increased, CMT decreased, FAZ area expanded, and AI decreased ( t=8.566, 16.739, -6.469, 9.719; P<0.001), the difference was statistically significant. There was no significant change in the blood flow density of FD-300 and overall SCP and DCP, and the difference was not statistically significant ( t=1.017, 1.197, 0.987; P>0.05). Compared with baseline, the FAZ area of RVO-ME eyes gradually expanded at 3 and 6 months after treatment, and the difference was statistically significant ( F=21.979, P<0.001). Correlation analysis results showed that BCVA at 6 months after treatment was positively correlated with the overall SCP and DCP blood flow density at baseline and 6 months after treatment ( r=-0.538, -0.484, -0.879, -0.854; P<0.05). There was a negative correlation with the area of FAZ 6 months after treatment ( r=0.544, P=0.001). The number of ME recurrences was negatively correlated with BCVA and overall SCP and DCP blood flow density 6 months after treatment ( r=0.604, -0.462, -0.528; P<0.05), it was positively correlated with FAZ area ( r=0.379, P=0.043). Conclusion:Within 6 months of IVA treatment in RVO-ME eyes, ME is significantly reduced and visual acuity is improved; SCP blood flow density decreases, and FAZ area expands.

Objective:To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China.Methods:A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014.Results:Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively.Conclusions:The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.