Objective To clarify the relationship between tumor necrosis factor alpha (TNF-α) and leptin in nonalcoholic fatty liver disease.Methods The real-time quantitative PCR (q-PCR) and enzymelinked immunosorbent adsorption experiment(ELISA) were used to detect the expression and correlation of TNFα and leptin in blood cells and serum from the normal group, non-alcoholic simple fatty liver(NAFL) group, nonalcoholic steatohepatitis (NASH) group and cirrhosis group.Results At the level of mRNA, the transcription of TNF-α in cirrhosis group was 14.03 times, 12.07 times and 11.05 times of the normal group, NAFL group and NASH group,and the difference was significant(P＜0.05).Leptin transcription of cirrhosis group was 1.95 times,0.79 times and 1.45 times of normal group, NAFL group and of NASH group(P＞0.05).And in the cirrhosis group, the expression of TNF-α was 7.52 times higher than Leptin (P＜ 0.01).In expression level of protein,TNF-α and leptin in cirrhosis group was 1.98 times and 2.39 times higher than the normal group, 1.24 times and 1.30 times higher than the NAFL group, 1.27 times and 1.37 times higher than NASH, and the difference was significant(P＜0.05).Moreover the expression of TNF-α was significantly higher than that of Leptinin groups above(P＜0.01).Conclusion TNF-α and Leptin are less expression in lymphocytes, but more expression in serum.And TNF-α and Leptin affect the evolution of NAFLD, and present a positive correlation, which lead to the occurrence of NAFLD.Comparing the two methods, detection of serum is more sensitive and more suitable for clinical study than lymphocyte.

Objective To investigate the expression of interleukin 6 (IL-6) in tumor microenvironment of natural killer/T cell lymphoma (NKTCL) and its relationship with clinical characteristics and prognosis. Methods From January 2005 to December 2012, 93 patients with NKTCL and available paraffin-embedded tissue in Sun Yat-sen University Cancer Center were included. The expression or IL-6 in tumor microenvironment was investigated by immunohistochemistry. The positive IL-6 expression was identified as≥10 cells/HP. The enumeration data and measurement data were compared by t test andχ2 test, respectively. Overall survival (OS) and progression free survival (PFS) were estimated with the Kaplan-Meier method. Survival rates were compared by the Log-rank test. Statistical significance was determined at a level of P<0.05. Results The median count of IL-6 positive cell number was 21 cells/HPF (range, 0-150 cells/HP), and 61.29%(57/93) patients were positive. Positive IL-6 expression was mostly associated with fever and high Korean prognostic index (KPI) score (both P< 0.05). The serum c-reactive protein (CRP) level was (29.28 ± 2.62) mg/L in IL-6 positive patients and (11.14±2.77) mg/L in IL-6 negative patients (t= -2.276, P= 0.025). Patients with negative IL-6 expression had better survival, with 52.7 % of 5-year PFS rate,and 60.0 % of 5-year OS rate; the 5-year PFS and OS rates in those with IL-6 positive were 23.6 % and 27.1 %, respectively (both P= 0.001). Conclusion The high expression of IL-6 in patients with NKTCL might be associated with adverse clinical feature and poor survival.

Objective To study anatomical structures of the maxillary second molars(MSM)roots and canals and the relationship between root apices and the maxillary sinus.Methods Cone beam computed tomography imaging data of 526 MSM from 263 patients were evaluated retrospectively.The patient age,number of roots and canals,number of fused roots,type of root canal curvature,and anatomical relationship to the sinus floor were all documented and analyzed.Results It was found that the majority of MSM had three roots(59.1%),and the incidence of three root canals with three roots was the highest(47.3%).Fused roots were found in 192(36.5%)of the teeth examined.Palatal root canals of two-root,two-canal,and three-root,three-canal teeth had more curvature in the buccolingual direction than in the mesiodistal direction.The mesial buccal roots of MSM with three roots tended to extend into the max-illary sinus and the palatine roots of the three-rooted MSM tended to separate from the maxillary sinus.The distance between MSM and the sinus floor increased with age(P＜0.05).Conclusion The root and canal shape of MSM varies widely among a sample of individu-als.

Objective To investigate the prevalence and influencing factors associated with frailty among institutional older adults and to provide evidence for intervention study.Methods A total of 237 older adults living in four welfare homes from Chengdu in Sichuan Province were recruited by convenience sampling.A cross-sectional survey was conducted,and frailty was assessed by the frailty phenotype;general information was collected by selfmade general information questionnaire;functional capacity was assessed by Barthel questionnaire;depressive status was assessed by GDS-15;cognitive function was assessed by clock drawing test and nutritional status was assessed by short form mini nutritional scale questionnaire (MNA-SF).Results The reported rate of frailty was 55.69％ among institutional older adults,and 44.31％ reported no frailty;grip weakness (207,87.3％),slow walking speed (172,72.6％) and low physical activity(131,55.3％) were the main frailty problems.Univariate analysis showed that the elderly'frailty conditions were different in the pre-retirement occupations,smoking,alcohol consumption,physical exercise,chronic diseases,medication,acute events (last year),self-reported health,using assisted walking devices,ability of daily life,depression,cognitive ability and nutritional status,and the differences were statistically significant(P＜0.05).Conclusion The status of frailty is not optimistic among institutional older adults and many factors are associated with frailty.Healthcare providers should pay more attention to the frailty issue and take timely intervention strategies to prevent or delay the frailty.

Objective:To analyze the clinical characteristics of HBeAg-negative chronic hepatitis B virus (HBV) infection in indeterminate phase with a low viral load.Methods:One hundred and thirty-nine cases with persistent normal alanine aminotransferase (ALT) and HBeAg-negative chronic HBV infection with low viral load who visited the Department of Infectious Diseases of the Affiliated Hospital of Yan'an University from September 2013 to July 2021 were retrospectively collected. Patients were divided into low hepatitis B surface antigen (HBsAg) group ( n=59) and high HBsAg group ( n=80) according to the baseline hepatitis B surface antigen (HBsAg) level. The changes of various indicators at baseline and follow-up endpoints were analyzed between the two groups. The rate of HBsAg decrease ≥0.5 log 10IU/ml, HBV DNA negative conversion rate, ALT persistently normal rate, and liver stiffness measurement (LSM) persistently normal rate at the end of the follow-up were compared. The t-test, or non-parametric Mann-Whitney U test, and Wilcoxon signed rank test were used for comparison of continuous data between the two groups. The χ2 test, or Fisher's exact probability method, was used for comparing count data between the two groups. Results:There were statistically significant differences in age, gender, and HBsAg at baseline, but there was no statistically significant difference in terms of family history of hepatitis B, follow-up time, anti-HBe, anti-HBc, HBV DNA, ALT, aspartate aminotransferase (AST), albumin (Alb), and LSM between the two groups. There were statistically significant differences in HBsAg, anti-HBc, and ALT levels before and after follow-up in the low HBsAg group, but no statistically significant differences in anti-HBe, HBV DNA, AST, Alb, and LSM levels. There were statistically significant differences in HBsAg and anti-HBc before and after follow-up in the high HBsAg group, but no statistically significant differences in anti-HBe, HBV DNA, ALT, AST, Alb, and LSM. A liver biopsy was performed in 66 patients during follow-up, and 27.27% of the patients had moderate liver damage. In the low HBsAg group, 45.76% of patients had a HBsAg decrease rate of ≥0.5 log 10IU/ml, 10.17% of patients had HBV DNA negative conversion, 88.14% of patients had a persistently normal ALT, and 96.61% of patients had a persistently normal LSM at the end of follow-up. In the high HBsAg group, 3.75% of patients had a HBsAg decrease of ≥0.5 log 10IU/ml, no patient had a HBV DNA negative conversion, 90% of patients had a persistently normal ALT, and 98.75% of patients had a persistently normal LSM. There were statistically significant differences in the HBsAg decrease rate (45.76% vs. 3.75%, χ2=32.975, P＜0.001) and HBV DNA negative conversion rate (10.17% vs. 0, χ2=6.219, P=0.013) between the two groups at the end of follow-up, but there were no statistically significant differences in the persistently normal ALT and LSM rates. Conclusion:The vast majority of patients with HBeAg-negative chronic HBV infection in the indeterminate phase with low viral load had persistent hypoviremia over the long term. Some patients have liver tissue damage and may progress to cirrhosis and liver cancer as a result of HBV DNA positivity, so antiviral treatment should be initiated in all.

Objective:To estimate the burden of hip fractures and related factors among the Chinese middle-aged and elderly population.Methods:Based on the data of China Health and Retirement Longitudinal Study (CHARLS) in 2015, the burden of hip fractures among Chinese middle-aged and elderly population was evaluated as the years lived with disability (YLD) rate. The relationship between gender, age (45-49, 50-59, 60-69 and ≥70 years old), educational level (no education, elementary school, junior high school, high school and above), region (urban, rural), gross domestic production (GDP) per capita (low, medium and high) and geographic area (northern, eastern, south-central, northwest and southwest regions) and the YLD rate of hip fractures were analyzed, respectively.Results:Excluding items with missing basic information and hip fracture data, a total of 17,830 subjects (8,405 males and 9,425 females) were included in the study with average age 61.6±9.8 years (range 45 to 105 years). The average age in male was 61.9±9.6 years, and that in female was 61.2±10.1 years. The prevalence of hip fractures was 2.3% (410/17,830). The total YLD rate was [694/100,000 (95% Uncertainty Interval ( UI): 462/100,000, 989/100,000)]. The YLD rates were similar between male [693/100,000 (95% UI: 461/100,000, 988/100,000)] and female [696/100,000 (95% UI: 463/100,000, 992/100,000)] subgroups. The YLD rate of hip fractures was increasing with age, which reached at maximum of 1,155/100,000 (95% UI: 769/100,000, 1,646/100,000) for participants aged 70 years or above. The rate was gradually decreased with the upgrade of the educational level. The participants with high school education and above reached the lowest of 434/100,000 (95% UI: 289/100,000, 619/100,000). In addition, the YLD rate of hip fractures in rural areas [721/100,000 (95% UI: 480/100,000, 1,027/100,000)] was higher than that in urban areas [650/100,000 (95% UI: 433/100,000, 926/100,000)]. The YLD rate in areas with higher GDP per capita [545/100,000 (95% UI: 363/100,000, 777/100,000)] was lower than that in areas with lower GDP per capita [761/100,000 (95% UI: 506/100,000, 1,084/100,000)]. Moreover, the participants living in the Northwest region were with the highest YLD rate of hip fractures [1,056/100,000 (95% UI: 703/100,000, 1,506/100,000)], followed by the Southwest region [887/100,000 (95% UI: 590/ 100,000, 1,264/100,000)] and the Northeast region [317/100,000 (95% UI: 211/100,000, 452/100,000)]. Conclusion:Hip fractures exerted heavy burdens on the Chinese middle-aged and elderly population. The YLD rate of hip fractures varied according to geographical regions, greater age, rural areas, low educational levels and low GDP per capita. These related factors could affect the disease burden of hip fractures in China.

Objective: To understand the basic information of anti-mitochondrial antibody (anti-AMA)-positive patients after initial diagnosis, and to set groundwork for further exploring the clinical significance of AMA in various diseases. Methods: Demographic data and related clinical information recorded through the Information System of Peking University People's Hospital from January 2013 to December 2016 were collected. Patients whose AMA and/or AMA-M2 first- tested as positive were recorded. Complications were classified according to the International Classification of Diseases. Results: A total of 1323 AMA positive cases were discovered for the first time. Among them, 78.0% were women, and the age of initial diagnosis was 56.8 ± 16.0 years. The first three initially diagnosed departments were rheumatology and immunology (37.4%), liver Disease (15.9%) and hematology (15.9%) relevant to musculoskeletal and connective tissue diseases (45.2%), hematology and hematopoietic organs and immune diseases (30.6%) and circulatory system diseases (29.7%). There were 297 newly confirmed cases of primary biliary cholangitis (PBC); accounting for 89.2% of women, and the age of initial diagnosis was 60.1 ± 12.4 years. The top three departments of initially diagnosed as PBC were liver disease (37.7%), rheumatology (33.0%) and gastroenterology (15.2%), of which 39.7% had musculoskeletal and connective tissue diseases, 27.9% had circulatory diseases, and 24.9 % were combined with endocrine and metabolic diseases. Conclusion Besides PBC and other autoimmune diseases, AMA and / or AMA-M2 positivity can be observed in a variety of diseases in several clinical departments, and its clinical significance remains to be further clarified.

Perimenopausal syndrome （MPS）， a common endocrine system disease， is one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in endocrinology， gynecology， and interdisciplinary fields of both Western and Chinese medicine to discuss the advantages and challenges of diagnosing and treating MPS with Western medicine， TCM， and integrative medicine. Experts at the conference believe that MPS is initiated by estrogen decline and rooted in deficiency， with the pathogenesis being imbalance between Yin and Yang in the kidney. The hormone replacement therapy in Western medicine for menopause can rapidly alleviate related symptoms by quickly restoring the estrogen level and timely detect and delay complications of menopause， whereas such a therapy has certain risks， necessitating close monitoring of adverse reactions. Moreover， the various contraindications and precautions limit the clinical application of the hormone replacement therapy. TCM has advantages in synergistically alleviating symptoms such as hot flashes， sweating， sleep disorders， and emotional abnormalities of MPS without causing obvious adverse reactions. However， its efficacy is slower than the hormone replacement therapy， and the TCM evidence for preventing and treating complications of menopause remains unclear. Three suggestions were proposed for the future development of both Western and TCM for ameliorating MPS. First， an integrated diagnosis and treatment system for MPS with both Western and Chinese medicine should be established. Second， high-quality evidence-based interventions for MPS should be developed with TCM alone or in combination with Western medicine. Third， efforts should be made to promote the new TCM drug development and the interdisciplinary cooperation for treating MPS.

Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
Pregnancy ; Female ; Animals ; Mice ; Tetraploidy ; Blastocyst ; Embryo, Mammalian ; Cell Differentiation ; Embryonic Development

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.