[Concomitant extragenital malformations of female reproductive tract anomalies: analysis of 444 cases in Peking Union Medical College Hospital].

Objective: To analyze the incidence and clinical phenotype of the concomitant extragenital malformations in the patients with female reproductive tract anomalies. Methods: A retrospective study was conducted using clinical data of hospitalized patients diagnosed with uterine, cervical, or vaginal malformations from January 2003 to December 2022 in Peking Union Medical College Hospital. The malformations were classified according to American Society for Reproductive Medicine müllerian anomalies classification 2021, and in each type, the incidence and specific manifestations of concomitant extragnital malformations were analyzed. Results: A total of 444 patients were included. The overall incidence of concomitant extragenital malformations was 43.5% (193/444), including urinary system, skeletal system, and other system malformations. Renal malformations on the obstructed side were present in all patients with oblique vaginal septum syndrome (100.0%, 78/78). The total incidence of concomitant extragnital malformations was as high as 8/11 in uterus didelphys, 43.5% (10/23) in unicornuate uterus, 33.6% (79/235) in Mayer-Rokitansky-Küster-Hauser syndrome, 18.8% (6/32) in septate uterus and 18.5% (12/65) in cervical agenesis. Urinary system malformations (30.6%, 136/444) and skeletal system malformations (13.5%, 60/444) were the most common concomitant malformations in all types, in which, unilateral renal agenesis and scoliosis were the most common. Conclusions: Urinary and skeletal system malformations are important features of female reproductive tract anomalies. Urologic ultrasonography and spinal roentgenogram are recommended for all patients with female reproductive tract anomalies.

[Association between digestive tract cancer and severity of coronary artery disease].

Objective: To evaluate the association between digestive tract cancer and anatomical severity of coronary artery disease. Methods: This study enrolled 142 patients with digestive tract cancer who underwent coronary angiography in the Department of Cardiology of the First Medical Center of Chinese PLA General Hospital from 2009 to 2020 as the cancer group. The patients in cancer group were matched with 426 non-cancer patients who underwent coronary angiography at our hospital during the same period in a 1∶3 ratio based on gender and age. All enrolled patients had no previous history of percutaneous coronary intervention or coronary artery bypass grafting surgery. The severity of coronary artery disease was documented and assessed using the SYNTAX score based on angiogram. High SYNTAX score (SXhigh) was defined as SYNTAX score≥22 (upper quartile), while low SYNTAX score (SXlow) was SYNTAX score<22. High NLR (NLRhigh) was NLR≥2.287 (median), while low NLR (NLRlow) was NLR<2.287. The association between digestive tract cancer and severity of coronary artery disease was analyzed using logistic regression analysis. Results: This study included a total of 568 patients, with a mean age of (66.6±8.7) years. Among them, 430 patients (75.7%) were male. The cancer group consisted of 142 patients with digestive tract cancers, with a mean age of (66.5±8.4) years. The non-cancer group consisted of 426 patients, with a mean age of (66.7±8.8) years. The proportion of SXhigh in patients with digestive tract cancers (33.1%, 47 patients) was higher than that in non-cancer patients (23.9%, 102 patients) (P=0.032). Compared to non-cancer patients, SXhigh in patients with digestive tract cancers was higher (OR: 1.614, 95%CI: 1.051-2.481, P=0.029). Subgroup analysis stratified by NLR levels revealed that in the NLRhigh group, patients with digestive tract cancers exhibited a higher severity of coronary artery disease compared to non-cancer patients, with an OR of 1.948 (95%CI: 1.005-3.779, P=0.048). In the NLRlow group, there was no significant relationship between digestive tract cancers and the severity of coronary artery disease, with an OR of 1.277 (95%CI: 0.586-2.781, P=0.538). Conclusions: Digestive tract cancer is associated with the severity of coronary artery disease, and patients with digestive tract cancers have a higher risk of severe coronary artery disease than non-cancer patients. Additionally, there is an association between digestive tract cancers and the severity of coronary artery disease under conditions of high levels of inflammation.

Tertiary Lymphoid Structure Raises Survival and Immunotherapy in HPV- HNSCC.

Immune checkpoint blockade (ICB) targeting PD-1/PD-L1 has been used for the treatment of head and neck squamous cell carcinoma (HNSCC). However, the overall response rate to ICB therapy for HNSCC remains less than 20%. It has recently been reported that the appearance of tertiary lymphoid structures (TLSs) in tumor tissue is correlated with better prognosis and response to ICB treatment. Here, we demonstrated an immune classification for the tumor microenvironment (TME) of HNSCC by analyzing The Cancer Genome Atlas (TCGA)-HNSCC data set and found that immunotype D with TLS enrichment had a better prognosis and response to ICB treatment. Furthermore, we observed that TLSs were present in a part of tumor samples of human papillomavirus (HPV) infection negative HNSCC (HPV- HNSCC) and were associated with the densities of dendritic cell (DC)-LAMP+ DCs, CD4+ T cells, CD8+ T cells, and progenitor T cells in TME. We established an HPV- HNSCC mouse model with TLS-enriched TME by overexpressing LIGHT in a mouse HNSCC cell line. We found that the induction of TLS formation enhanced the response to PD-1 blockade treatment in the HPV- HNSCC mouse model, accompanied by increases in DCs and progenitor exhausted CD8+ T cells in the TME. Elimination of CD20+ B cells attenuated the therapeutic effect of PD-1 pathway blockade in TLS+ HPV- HNSCC mouse models. These results indicate that TLSs contribute to the favorable prognosis and antitumor immunity of HPV- HNSCC. Inducing TLS formation in HPV- HNSCC tumors is a potential therapeutic method for improving the ICB response rate in patients with HPV- HNSCC.

[Risk factors and predictors of persistent ectopic pregnancy after interstitial pregnancy surgery].

Objective: To explore the related factors and early predictors of persistent ectopic pregnancy (PEP) in patients with interstitial pregnancy after operation. Methods: The clinical data of patients with interstitial pregnancy who underwent surgery in the Department of Obstetrics and Gynecology of Peking Union Medical College Hospital from January 2013 to August 2021 were collected. Patients were divided into two groups according to whether PEP occurred (8 patients in PEP group and 124 patients in non-PEP group). Using propensity score matching (PSM) analysis, the basic data, surgical methods, the ratio of postoperative to preoperative serum ß-human chorionic gonadotropin (ß-hCG), the duration of when the serum ß-hCG had decreased to normal after the operation were compared and analyzed to find the related factors of PEP after interstitial pregnancy surgery. The sensitivity and specificity of the ratio of 24-48 hours postoperative ß-hCG to preoperative ß-hCG in predicting postoperative PEP were evaluated by drawing receiver operating characteristic (ROC) curve. Results: Before PSM, the ages of patients in PEP group and non-PEP group were (30.0±4.0) and (32.4±5.0) years old, respectively, P>0.05. After PSM, 8 PEP patients in the study group and 29 patients in the control group were matched successfully, and the ages of the two groups were (30.0±4.0) and (30.1±3.2) years old, respectively, P>0.05. After PSM, there was no significant difference in gravidity, parity, menopausal days, preoperative ß-hCG level and maximum diameter of lesions, all P>0.05. After PSM, the proportion of patients with maximum diameter ≤ 2.6 cm in PEP group (6/8) was significantly higher than that in control group (31.0%, 9/29), P=0.025. The median (Q1, Q3) of the ratio of 24-48 hours postoperative ß-hCG to preoperative ß-hCG ratio was 52.9% (49.9%, 59.7%) in the PEP group, which was significantly higher than 31.5% (23.8%, 39.0%) in the control group (P=0.001); The median (Q1, Q3) of duration of when the serum ß-hCG had decreased to normal after the operation in PEP group was 52.0 (34.8, 92.0) d, which was significantly higher than 24.0 (20.5, 31.0) d in control group (P<0.001). The ROC-Area Under Curve of the ratio of 24-48 hours postoperative ß-hCG to preoperative ß-hCG ratio for predicting postoperative PEP in the two groups was 0.892 (95%CI: 0.725-1.000, P=0.001). The cut-off value for predicting PEP was 48.5%, where the diagnostic sensitivity was 87.5%, the specificity was 93.1%. Conclusions: In the operation of interstitial pregnancy, the maximum diameter of lesion ≤ 2.6 cm is a related factor for postoperative PEP. There was no significant difference in the risk of PEP between cornuotomy and cornectomy. The ratio that 24-48 hours postoperative ß-hCG/preoperative ß-hCG ratio greater than 48.5% was a reference index for predicting postoperative PEP and guiding treatment.

GSDME Is Related to Prognosis and Response to Chemotherapy in Oral Cancer.

Gasdermin E (GSDME), as the major executive protein of pyroptosis, has been considered to be linked to antitumor immunity in recent years. However, the role of GSDME in oral squamous cell carcinoma (OSCC) remains to be elucidated. Here, by using a human OSCC tissue microarray, human OSCC tissue, and Tgfbr1/Pten conditional knockout mice, we found that GSDME was strongly expressed in OSCC and that GSDME expression in primary tumors was higher than that in metastatic lymph nodes. In addition, GSDME expression in OSCC was positively related to better prognosis. Moreover, GSDME-mediated pyroptosis occurred upon stimulation with chemotherapy drugs, and functional knockdown of GSDME attenuated the cisplatin-induced antitumor effect. Consistent with these results, bioinformatic analysis indicated that GSDME expression was positively correlated with the sensitivity of a number of antitumor drugs approved by the US Food and Drug Administration. Inhibition of GSDME expression by small interfering RNA in SCC7 cells significantly increased the expression of the cancer stem cell markers, CD44 and ALDH1. Furthermore, multiplexed immunohistochemistry and flow cytometry indicated that the expression of GSDME positively correlated with tumor-infiltrating CD8+ T cells, granzyme B, and M1 phenotype macrophages. Collectively, these findings demonstrated that GSDME is a potential positive prognostic factor of OSCC, and GSDME-mediated pyroptosis induced by chemotherapy plays a role in antitumor response.

[Clinical significance and pathogenesis analysis of heterogeneous nuclear ribonucleoprotein U in acute myeloid leukemia].

Objective: To investigate the clinical significance and pathogenesis of heterogeneous nuclear ribonucleoprotein U (hnRNP U) in acute myeloid leukemia (AML) . Methods: The expression of hnRNP U, an RNA binding protein, in patients with AML and healthy controls was compared based on the Gene Expression Profiling Interactive Analysis database and the data of the center. The Beat AML Dataset (n=158) was downloaded from the cBioPortal database. The hnRNP U expression level was divided into the high-expression group (n=89) and low-expression group (n=69) , and patients' clinical characteristics were compared. The effect of hnRNP U on the biological behavior of human AML cell lines was studied by Cell Counting Kit-8 assay to detect cell proliferation. Annexin Ⅴ-APC/7-AAD antibodies were used to detect cell apoptosis. DNA content (PI staining) was quantitatively analyzed to detect cell cycle changes, and colony formation experiments were performed to detect cell cloning formation ability after hnRNP U knockdown in Kasumi-1 and MOLM-13 cells. To study the effect of hnRNP U knockdown on the DNA damage response (DDR) pathway proteins of cleaved-PARP, immunoblot analysis using p-H2A.X was conducted. Results: ①Pan-cancer analysis showed that hnRNP U was highly expressed in patients with AML, and the expression level of hnRNP U mRNA in peripheral blood mononuclear cells was significantly higher in patients with AML than in healthy controls (0.0315±0.0042 vs 0.0195±0.0006, respectively, P<0.01) . ②The age of onset was 56 (2-87) years in the high-expression group and 65 (8-85) years in the low-expression group (t=-2.681, P=0.007) . Moreover, the high-expression group had a higher proportion of combined FLT3 mutations than the low-expression group (χ(2)=4.069, P=0.044) . ③Compared with the negative control, hnRNP U knockdown inhibited the proliferation (P<0.001 and P<0.001) , promoted the apoptosis (P<0.01 and P<0.001) , decreased the colony formation ability (P<0.001 and P<0.001) , and arrested the cell cycles in the G(2)/M phase (P<0.05 and P<0.01) of Kasumi-1 and MOLM-13 cells, respectively. ④hnRNP U knockdown could increase the protein expression of cleaved-PARP and p-H2A.X on the DDR pathway. Conclusion: hnRNP U is highly expressed in AML, and hnRNP U knockdown can inhibit the occurrence and development of AML possibly through the activation of the DDR pathway.

[Clinical analysis of surgical treatment of cornual pregnancy of 109 cases].

Objective: To study the clinical characteristics of cornual pregnancy and compare the effects of various surgical methods on the outcomes. Methods: This was a single-center retrospective study. The clinical records of patients with cornual pregnancy who underwent surgery in Peking Union Medical College Hospital from June 2012 to December 2020 were collected. Surgical interventions included curettage (guided by ultrasound or monitored by laparoscope), and cornuostomy/cornectomy (the surgical approach by laparoscopy or laparotomy). The baseline data, perioperative treatment and whether persistent ectopic pregnancy (PEP) occurred after surgery were collected and analyzed statistically. Results: A total of 109 patients with cornual pregnancy diagnosed by surgical treatment were included in this study, whose average age was (32.9±4.8) years. Among them, the incidence of postoperative PEP was 16.5% (18/109). The risk of PEP in multipara was significantly higher than that in nulliparous women (OR=7.639, 95%CI: 2.063-28.279, P=0.001). The risk of PEP in patients with the maximum diameter of lesion<1.5 cm was significantly higher than that in patients with the maximum diameter of lesion≥1.5 cm (OR=8.600, 95%CI: 2.271-32.571, P=0.002). Among all surgical approaches for cornual pregnancy, the proportion of PEP in curettage under ultrasound monitoring was the highest (56.0%, 14/25), which was higher than that in curettage under laparoscope monitoring (1/10; χ2=6.172，P=0.013); the proportion of PEP in curettage group (42.9%, 15/35) was higher than that in cornuostomy/cornectomy group (4.1%, 3/74; χ2=25.950，P<0.01). Neither salpingectomy in the operation nor the routine use of methotrexate (MTX) in perioperative period could significantly reduce the incidence of PEP (all P>0.05). Conclusions: Among the patients with cornual pregnancy, multipara, the maximum diameter of lesion<1.5 cm and ultrasound-guided curettage are the risk factors of PEP after operation. Cornuostomy or cornectomy is recommended for patients with cornual pregnancy. If the patients would perform the curettage operation, laparoscopic monitoring is recommended. For patients with possible satisfactory operation outcome, it is not recommended to use MTX as a routine preventing measure.

[Prevalence, patterns and long-term changes of multimorbidity in adults from 10 regions of China].

Objective: To describe the prevalence of multimorbidity and its secular trend, and to explore the common patterns of multimorbidity in Chinese adults. Methods: A total of 25 033 participants who attended the second resurvey of China Kadoorie Biobank (CKB) were included in the study. We used data collected both at baseline (2004-2008) and at resurvey (2013-2014). A total of 13 chronic conditions were included, defined by self-reported, physical examination, and blood sample testing. Multimorbidity was defined as co-existence of two or more chronic conditions. Patterns of multimorbidity were explored using hierarchical cluster analysis. Results: The mean age of participants was (51.5±10.1) years at baseline and (59.5±10.2) years at second resurvey. The prevalence of multimorbidity increased from 33.5% to 58.1% over (8.0±0.8) years of follow-up. The average number of chronic conditions per person increased from 1.15 to 1.82 and all participants increased 0.42 conditions per 5 years on average. Participants who were older, less educated or lived in urban areas had a higher prevalence of multimorbidity and a higher increase in the number of chronic conditions. The increase in the number of chronic conditions was also higher among smokers and heavy alcohol drinkers. The most common multimorbidity pattern in the present population consisted of obesity, hypertension, diabetes, stroke, and heart disease. Conclusions: The prevalence of multimorbidity in Chinese adults is increasing rapidly due to ageing population. Populations of different sociodemographic background and lifestyle habits may have different prevalence of multimorbidity and changes in rates over time.

[Comparison of Fried phenotype and frailty index and their associations with risk of mortality].

Objective: To compare the consistency of frailty status measured by Fried phenotype and frailty index composed of different numbers of deficits, and their prospective associations with risk of mortality. Methods: Data of 23 615 participants from the second resurvey of the China Kadoore Biobank (CKB) was used. Fried phenotype was constructed using five phenotypes, and frailty indexes (FI) were constructed using 28 and 40 deficits, respectively. We calculated the Weighted Kappa coefficient to compare the consistency of three measures in the classification of frailty status. Cox regression was performed to analyze the association of frailty status with risk of mortality. Results: The frailty prevalence calculated by Fried phenotype, FI-28, and FI-40 were 5.4%, 7.9%, and 4.0%, respectively. The Kappa coefficients of Fried phenotype with FI-28 and FI-40 were 0.357 and 0.408, respectively. The Kappa coefficients of FI-28 and FI-40 was 0.712. During an average of (3.9±0.5) years of follow-up, 755 participants died. When Fried phenotype was used, compared with the robust participants, the prefrail and frail participants had increased risk of mortality, the multivariable-adjusted HRs were 1.60 (95%CI: 1.32-1.94) and 2.90 (95%CI: 2.25-3.73), respectively. When FI-28 was used, the corresponding HRs were 1.71 (95%CI: 1.39-2.11) and 2.52 (95%CI:1.95-3.27) for prefrail and frail participants, and when FI-40 was used, the corresponding HRs were 1.98 (95%CI:1.60-2.44) and 3.71 (95%CI: 2.80-4.91). The association of frailty status with mortality differed in different age groups, with the association stronger in younger adults than in older adults. Conclusion: Fried phenotype and frailty index constituted with different numbers of deficits showed good consistency; which can be used to well predict the risk of mortality.

[Transitions on frailty status and related risk factors for its status worsening: finding from the Beijing MJ Health Screening Center].

Objective: To evaluate the transitions of frailty status and related factors influencing its worsening in middle-aged and elderly adults. Methods: Data was obtained from the Beijing MJ Health Screening Center. A total of 13 689 participants who attended health checkups at least twice during 2008-2019 and had more than three years' intervals during these two health checkups were included in the study. The frailty index comprising 28 variables was used to measure frailty status. Frailty was defined as frailty index ≥0.25, and prefrailty was defined as frailty index >0.10 and <0.25. Logistic regression analysis was performed to investigate the association of socio-demographic factors and lifestyle characteristics with the worsening of frailty status, stratified by frailty status at the first health checkup. Results: The mean age at the first and last health checkups were (42.3±9.2) and (47.9±9.3) years, respectively. The mean interval during these two health checkups was (5.7±1.9) years. At the first health checkup, the prevalence of frailty and prefrailty were 2.5% and 50.3%, respectively. While at the last health checkup, the prevalence of frailty and prefrailty rose to 3.9% and 55.4%. Of all participants, 67.3% remained in the same frailty state, 21.2% worsening, and 12.5% improving. In robust participants at the first health checkup, older age, female, low education level, smoking cessation, daily smoking, being general obesity measured by BMI or central obesity measured by WHR showed an increased the risk of worsening frailty status. However, in prefrail participants at the first health checkup, older age, female, general, or central obesity presented as risk factors for worsening frailty status. Conclusion: Modifiable factors such as low education level, smoking, and obesity may increase the risk of worsening frailty status.

[The prognostic value of myocardial infarct size measured by cardiovascular magnetic resonance in patients with acute ST-segment elevation myocardial infarction].

Objective: To investigate the prognostic value of infarct size (IS) in patients with acute ST-segment elevation myocardial infarction (STEMI) underwent primary percutaneous coronary intervention (PCI). Methods: A total of 104 patients with acute STEMI who underwent primary PCI treatment in Shengjing Hospital of China Medical University from February 2017 to November 2018 were included in the present study. All patients underwent cardiovascular magnetic resonance (CMR) within one week after primary PCI treatment. The subjects were followed up for two years. Major adverse cardiac events (MACE) included new onset congestive heart failure and/or recurrent nonfatal myocardial infarction and/orcardiac death. The optimal IS cutoff value for MACE was determined by receiver operating character (ROC) curve. Based on the IS cutoff value, the patients were divided into the high IS group and the low IS group. Clinical characteristics between the two groups were compared. A cox regression model was used to analyze the prognostic value of IS in acute STEMI patients treated with primary PCI for the adverse events. Results: The IS cutoff value determined by ROC curve was 13.55%. 50 patients were in the high IS group (IS≥13.55%) and 54 patients were in the low IS group (IS<13.55%). More female patients [14 cases (28.0%) vs. 6 cases (11.1%)] were in the IS group, and a higher proportion of patients in the high IS group had anterior myocardial infarction [27 cases (54.0%) vs. 16 cases (29.6%)] or microvascular obstruction [32 cases (64.0%) vs. 16 cases (29.6%)]. White blood cell counts [11.25(8.90, 13.38) ×109/L vs. 9.25(7.58, 11.00) ×109/L], troponin I levels [50.63(16.56, 76.30)µg/L vs. 16.58(2.66, 38.42)µg/L] and brain natriuretic peptide levels [178.10(79.70, 281.95)µg/L vs. 79.60(42.83, 183.90)µg/L] in the high IS group were higher than those in the low IS group (P<0.05), and left ventricular ejection fraction [(45.15±10.65)% vs. (51.95±12.91)%] in the high IS group was lower than that in the low IS group (P<0.05). Multivariate Cox regression analyses showed that IS was independently associated with the risk of cardiac death in patients with acute STEMI two years after primary PCI(P=0.033, HR=1.075, 95%CI1.006-1.148). Every 1% increase in IS was associated with a 7.5% increase in cardiac death. Conclusions: Infarct size, measured by CMR within one week after primary PCI, is strongly associated with cardiac death in patients with acute STEMI two years after primary PCI. IS could be used as an index for the prognosis of patients with acute STEMI.

[Application of deep learning neural network in pathological image classification of non-inflammatory aortic membrane degeneration].

Objective: To investigate the value of deep learning in classifying non-inflammatory aortic membrane degeneration. Methods: Eighty-nine cases of non-inflammatory aortic media degeneration diagnosed from January to June 2018 were collected at Beijing Anzhen Hospital, Capital Medical University, China and scanned into digital sections. 1 627 hematoxylin and eosin stained photomicrographs were extracted. Combined with the ResNet18-based deep convolution neural network model, 4-category classification of pathological images were performed to diagnose the non-inflammatory aortic lesion. Results: The prediction model of artificial intelligence assisted diagnosis had the best accuracy, sensitivity and precision in identifying lesions with smooth muscle cell nuclei loss, which were 99.39%, 98.36% and 98.36%, respectively. The classification accuracy of elastic fiber fragmentation and/or loss lesions was 98.08%, while that of intralamellar mucoid extracellular matrix accumulation lesions was 96.93%. The overall accuracy of the classification model was 96.32%, and the area under the curve was 0.982. Conclusions: The accuracy of deep learning neural network model in the 4-category classification of non-inflammatory aortic lesionsis confirmed based on digital photomicrographs. This method can effectively improve the diagnostic efficiency of pathologists.

[Study on the expression of p62 protein in patients with lung adenocarcinoma].

To explore the expression of p62 protein in lung adenocarcinoma (LUAD). In this study, a cross-sectional study was adopted. From December 2011 to May 2013, 60 patients with lung adenocarcinoma who were diagnosed and treated in Tongji Hospital of Tongji University, Shanghai were selected for paraffin embedding and tissue chip preparation, and immunohistochemistry (IHC) technology was used to detect the expression of p62 in lung adenocarcinoma patients' cancer tissues and adjacent tissues, and analyze the relationship between p62 expression and the clinicopathological characteristics and survival prognosis of patients with lung adenocarcinoma; at the same time, 6 cases of lung adenocarcinoma were selected by random sampling cancer tissues and adjacent tissues were detected by Western Blot (WB) to detect p62 protein and analyzed by gray value. Preoperative examination specimens of inpatients with lung adenocarcinoma diagnosed from April 2018 to early October 2019, and plasma specimens of healthy subjects were collected, and enzyme linked immunosorbent assay (ELISA) was used to detect lung adenocarcinoma patients and healthy patients. The expression of p62 in the plasma of the subjects was statistically analyzed using SPSS 22.0 software. The results of IHC showed that the positive expression rate of p62 in cancer tissues was significantly higher than that in adjacent tissues, and the difference was statistically significant (t=5.593, P<0.001). Similarly, WB results showed that the expression of p62 protein in cancer tissues was significantly higher than that in adjacent tissues. It is statistically relevant (t=2.238, P=0.049). The expression of p62 was statistically correlated with tumor size, clinicopathological stage and lymph node metastasis in patients with lung adenocarcinoma (all P<0.05). The overall survival of patients with lung adenocarcinoma with high p62 expression was worse than that of patients with low p62 expression (95%CI was 0.238-0.870, P=0.028), suggesting that the high expression of p62 is related to the poor prognosis of patients with lung adenocarcinoma. The level of p62 protein in the plasma of patients with lung adenocarcinoma was significantly higher than that in the healthy control group. The difference was statistically significant (t=8.533, P<0.001). The area under the receiver operating characteristic curve was 0.835 (95%CI was 0.779-0.891, P<0.001), which is significantly higher than CEA, CA125, CA153 and other single traditional indicators, and the combined detection of four indicators has the highest diagnostic efficiency. p62 was strongly expressed in cancer tissues and serum, which is related to the poor prognosis and overall survival rate of LUAD patients.

Sacrocolpopexy compared with transvaginal mesh surgery: a systematic review and meta-analysis.

BACKGROUND: The use of mesh is controversial in the treatment of female pelvic organ prolapse. OBJECTIVES: To systematically review the outcomes of sacrocolpopexy compared with transvaginal mesh surgery and to provide evidence-based suggestions. SEARCH STRATEGY: The MEDLINE, EMBASE, Cochrane Library and clinicaltrials.gov databases were searched on 21 November 2018. SELECTION CRITERIA: Randomised controlled trials and prospective and retrospective cohort studies were included. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer and examined by a second reviewer for accuracy. Odds ratios and 95% CI were calculated using random-effects models. MAIN RESULTS: Twenty comparative studies were included. The meta-analysis was performed with subgroups. The summary odds ratios of the randomised controlled group were 1.84 (95% CI 0.79-4.29, I2  = 75%) for anatomical success, 1.41 (95% CI 0.47-4.24, I2  = 38%) for subjective success, 0.42 (95% CI 0.18-0.98, I2  = 0%) for mesh complications, 0.61 (95% CI 0.20-1.91, I2  = 0%) for prolapse reoperation and 0.44 (95% CI 0.23-0.88, I2  = 0%) for de novo dyspareunia. The mean differences were 0.77 (95% CI 0.31-1.23, I2  = 66%) for total vaginal length and -1.28 (95% CI -2.00 to -0.55, I2  = 66%) for point C after surgery. CONCLUSIONS: Very-low-quality evidence indicated that the anatomical and subjective success rates of sacrocolpopexy were similar to those of transvaginal mesh surgery; sacrocolpopexy might be more beneficial than transvaginal mesh surgery in terms of mesh-related complication rates, prolapse recurrence and de novo dyspareunia. However, additional high-quality randomised trials with long-term follow-up durations are needed. TWEETABLE ABSTRACT: Sacrocolpopexy is beneficial after surgical anatomical changes and has decreased rates of mesh-related complications and dyspareunia.

[Clinical analysis of 68 cases of sepsis during pregnancy and the postpartum period].

Objective: To investigate the clinical features, etiology, and prognosis of sepsis during pregnancy and the postpartum period. Methods: Sixty-eight pregnant women with maternal sepsis treated in Peking Union Medical College Hospital from January 1997 to December 2019 were collected, and divided into obstetric infection group (30 cases) and non-obstetric infection group (38 cases) according to different infection sources. Clinical manifestations, types of infection sources, microbiological characteristics, treatment and outcomes were studied and analyzed. Results: (1) General conditions and clinical features: sepsis occurrence rate was 57% (39/68) and 43% (29/68) in prenatal and postpartum period, repectively. Statistical analysis showed that incidence of respiratory, renal, liver and coagulation dysfunction in non-obstetric infection group were significantly higher than those in obstetric infection group, and multiple organ dysfunction, cardiac arrest and blood lactate≥4 mmol/L were more common (all P<0.05). Sequential organ failure score in non-obstetric infection group was also significantly higher than that in obstetric infection group (P<0.05). (2) Types of infection sources and microbiological characteristics: the most common maternal sepsis was genital tract sepsis (37%, 25/68). Chorioamnionitis was the most common cause in obstetric sepsis (40%, 12/30), while intra-abdominal infection was the most common cause in non-obstetric sepsis (34%, 13/38). Thirty-seven patients (54%, 37/68) were diagnosed as bloodstream infection (BSI). Gram-negative bacteremia accounted for 70% (26/37), the most common pathogen of which was Escherichia coli. BSI was most commonly secondary to a genital tract infection (65%, 17/26). (3) Treatment: the ICU hospitalization rates and the utilization rate of mechanical ventilation and vasoactive agents in non-obstetric group were higher than those in obstetric group with significant differences (all P<0.05). Thirty-two patients (47%, 32/68) underwent surgery to remove the infection sources, including 5 cases of hysterectomy. (4) Prognosis: the case fatality rate of maternal sepsis was 19% (13/68), which was significantly higher in the non-obstetric infection group (29%,11/38) compared with the obstetric infection group (7%,2/30; P=0.020). The time from diagnosis of sepsis to termination of pregnancy was (5.5±8.6) days in prenatal women, and time in obstetric infection group [(1.9±2.2) days] was significantly less than that of non-obstetric infection group [(7.7±10.3) days, P=0.029]. Adverse pregnancy outcomes were higher in the first and second trimester (72%, 18/25) than in the third trimester (21%, 3/14), and the difference was statistically significant (P=0.002). Conclusions: Sepsis during pregnancy and the postpartum period is a potentially life-threatening disease. Pregnant women with non-obstetric sepsis have more complications, more serious condition and worse prognosis than those with obstetric infection. Timely detection of risk factors, early identification and active treatment are helpful to improve maternal and fetal prognosis.

[Association between height loss and calcaneus bone mineral density in Chinese adults].

Objective: To examine the association between height loss and calcaneus bone mineral density (BMD) through data gathered from the China Kadoorie Biobank (CKB). Methods: The present study included 24 231 participants who attended the CKB resurvey during 2013-2014, in which calcaneus BMD was measured by quantitative ultrasound method for the first time. Height loss was calculated according to the differences appeared in height measurement between baseline and resurvey. We used linear regression models to estimate the association between height loss and BMD measures. Results: The mean interval between baseline and resurvey was (8.0±0.8 ) years. 33.0% of the participants showed a height loss of ≥1.0 cm, and another 3.7% were with height loss of ≥3.0 cm. After adjustment for potential confounders, there was a linear correlation seen between height loss and BMD (P for all linear trend were <0.001). The ßs (95%CIs) for each 1.0 cm of height loss were -0.79 (-0.95--0.63) for broadband ultrasound attenuation (BUA), -2.74 (-3.35--2.13) for speed of sound (SOS), and -1.29 (-1.54--1.04) for stiffness index (SI). Compared with participants with stable height, the multivariate-adjusted ßs (95%CIs) for those with height loss of ≥3.0 cm were -3.29 (-4.08--2.50) for BUA, -10.70 (-13.66--7.73) for SOS, and -5.16 (-6.36--3.96) for SI, respectively. According to the subgroup analyses, the association of height loss with BMD measures seemed to be more apparent among females, in those aged ≥55 years, and those being less physically active. Conclusions: BMD became lower with the increase of height loss. Regular height measurement may contribute to the early diagnosis and prevention of osteoporosis.

Patient-derived organoids of non-small cells lung cancer and their application for drug screening.

Patient-derived organoids (PDOs) are emerging as preclinical models with promising values in personalized cancer therapy. The purpose of this study was to establish a living biobank of PDOs from patients with non-small cell lung cancer (NSCLC) and to study the responses of PDOs to drugs. PDOs derived from NSCLC were cultured in vitro, and then treated with natural compounds including chelerythrine chloride, cantharidin, harmine, berberine and betaine with series of concentrations (0.5-30 µM) for drug screening. Phenotypic features and treatment responses of established PDOs were reported. Cell lines (H1299, H460 and H1650) were used for drug screening. We successfully established a living NSCLC organoids biobank of 10 patients, which showed similar pathological features with primary tumors. Nine of the 10 patients showed mutations in EGFR. Natural compounds chelerythrine chloride, cantharidin and harmine showed anticancer activity on PDOs and cell lines. There was no significant difference in the 95% confidence interval (CI) for the IC50 value of chelerythrine chloride between PDOs (1.56-2.88 µM) and cell lines (1.45-3.73 µM, p>0.05). PDOs were sensitive to berberine (95% CI, 0.092-1.55 µM), whereas cell lines showed a resistance (95% CI, 46.57-2275 µM, p<0.0001). PDOs had a higher IC50 value of cantharidin, and a lower IC50 value of harmine than cell lines (p<0.05, 7.50-10.45 µM and 4.27-6.50 µM in PDOs, 3.07-4.44 µM and 4.69-544.99 µM in cell lines, respectively). Both PDOs and cell lines were resistant to betaine. Chelerythrine chloride showed the highest inhibitory effect in both models. Our study established a living biobank of PDOs from NSCLC patients, which might be used for high-throughput drug screening and for promising personalized therapy design.