Background: Twenty-four-hour urinary free cortisol (UFC) measurement is the initial diagnostic test for Cushing’s syndrome (CS). We compared UFC determination by both direct and extraction immunoassays using Abbott Architect, Siemens Atellica Solution, and Beckman DxI800 with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, we evaluated the value of 24-hr UFC measured by six methods for diagnosing CS. Methods: Residual 24-hr urine samples of 94 CS and 246 non-CS patients were collected.A laboratory-developed LC-MS/MS method was used as reference. UFC was measured by direct assays (D) using Abbott, Siemens, and Beckman platforms and by extraction assays (E) using Siemens and Beckman platforms. Method was compared using Passing–Bablok regression and Bland–Altman plot analyses. Cut-off values for the six assays and corresponding sensitivities and specificities were calculated by ROC analysis. Results: Abbott-D, Beckman-E, Siemens-E, and Siemens-D showed strong correlations with LC-MS/MS (Spearman coefficient r = 0.965, 0.922, 0.922, and 0.897, respectively), while Beckman-D showed weaker correlation (r = 0.755). All immunoassays showed proportionally positive bias. The areas under the curve were 0.975 for Abbott-D, 0.972 for LCMS/MS, 0.966 for Siemens-E, 0.948 for Siemens-D, 0.955 for Beckman-E, and 0.877 for Beckman-D. The cut-off values varied significantly (154.8–1,321.5 nmol/24 hrs). Assay sensitivity and specificity ranged from 76.1% to 93.2% and from 93.0% to 97.1%, respectively. Conclusions Commercially available immunoassays for measuring UFC show different levels of analytical consistency compared to LC-MS/MS. Abbott-D, Siemens-E, and Beckman-E have high diagnostic accuracy for CS.

Objective:To estimate the longitudinal association between serum lipid biomarkers and the development of cardiometabolic multimorbidity (CMM) in middle-aged and old adults (≥45) in China, while examining effect differences among degree of dyslipidemia aggregation and various dyslipidemia combination patterns.Methods:Based on data from the China Health and Retirement Longitudinal Study (2011-2018), logistic regression analysis was used to evaluate the associations of TC, LDL-C, HDL-C, TG (4 forms of dyslipidemias), degree and pattern of dyslipidemia combination with CMM. We also used restricted cubic splines to show the dose-response associations between 4 lipid biomarkers and CMM development.Results:Of the 6 522 participants included, 590 (9.05%) developed CMM. After adjusting for covariates, all 4 forms of dyslipidemias were positively associated with CMM development (high TC: OR=1.33, 95% CI: 1.03-1.71; high LDL-C: OR=1.35, 95% CI: 1.05-1.75; low HDL-C: OR=1.45, 95% CI: 1.19-1.77; high TG: OR=1.50, 95% CI: 1.20-1.88). The U-shaped dose-response relationship between LDL-C and CMM development was observed ( P for non-linear =0.022). The odds of CMM increased with the increase of dyslipidemias forms, which was highest in those with ≥3 forms of dyslipidemias ( OR=2.02, 95% CI: 1.33-3.06). In various dyslipidemia form combinations, the possibility of CMM development was highest in those with high TC, high LDL-C and low HDL-C ( OR=3.54, 95% CI: 1.40-8.67). High TC and high LDL-C were significantly associated with CMM development in people without cardiometabolic diseases. Low HDL-C was positively associated with diabetes and CMM development in participants without cardiometabolic diseases, cardiovascular disease (CVD) followed by diabetes, and diabetes followed by CVD. High TG was positively associated with diabetes and CMM in participants without cardiometabolic diseases, and diabetes followed by CVD. Conclusions:A total of 4 forms of dyslipidemia were all independently associated with CMM development in middle-aged and old adults in China. The dose-response relationship between LDL-C level and CMM development was U-shaped. The aggregation of 4 forms of dyslipidemia were associated with the development of CMM. Low HDL-C and high TG were significantly associated with multiple patterns of cardiometabolic diseases development.

Objective To advance China's foreign medical work to a new level by comparing medical teams from Japan,the United States,and India,focusing on transforming and upgrading to international development cooperation.Methods Liter-ature and data on the foreign medical teams of the three countries were retrieved and compared in five aspects:institutional mech-anisms,forms of assistance,foreign medical training,traditional medicine assistance,and evaluation of assistance effectiveness.Results Among the three countries,Japan and the United States showed minor differences in their approaches to foreign medical assistance,while India exhibited a distinct pattern.Conclusion China can enhance the international profile of its medical teams,consider both domestic and international interests,and continuously refine the overall strategy for foreign medical aid.Specifically,the country needs to optimize China's contribution to global health by way of strengthening international health ex-changes and cooperation and establishing a 5G smart medical technology platform for remote assistance.

By reviewing the ancient and modern literature， the name， origin， medicinal parts and other aspects of Linderae Radix in famous classical formulas were systematically sorted out， so as to provide a basis for development of famous classical formulas containing this herb. Linderae Radix was first recorded in Bencao Shiyi in the Tang dynasty under name of Pangqi， and since Rihuazi Bencao of the Five dynasties， all generations of materia medica have used Wuyao as its proper name of the herb. The mainstream source of Linderae Radix used in the past dynasties is dried tuberous roots of Lindera aggregata contained in the 2020 edition of Chinese Pharmacopoeia. The origins of Linderae Radix recorded in the past dynasties are mainly Guangdong， Guangxi， Hunan， Zhejiang， Anhui and others， since the Song dynasty， Tiantai county in Zhejiang province has been regarded as the authentic producing place， in modern times， it is still the authentic place of origin. At harvesting， in ancient times， the harvesting time of the roots was mostly in August， while in modern times， Linderae Radix is mostly harvested in winter and spring or throughout the year， and is dried directly after harvesting or cut thin slices and dried in the place of production. At processing， Linderae Radix was processed by removing the peel and heart， wine roasting， vinegar roasting and other methods in ancient times， and in modern times， it is mostly used in raw form as medicine. In conclusion， it is suggested that the processing method of fresh slicing and drying in the place of origin in the 2020 edition of Chinese Pharmacopoeia should be adopted if Linderae Radix is involved in the development of famous classical formulas.

Objective:To evaluate the safety and efficacy of amniotic membrane patching in the treatment of recurrent macular hole associated with retinal detachment of high myopia (MHRD).Methods:A prospective study. From March 2018 to January 2020, 11 patients (11 eyes) of recurrent macular hole associated with MHRD at the First Affiliated Hospital of Zhengzhou University were enrolled. Among them, there were 3 males (3 eyes), and 8 females (8 eyes). The average age was 63.64±5.82. The axis length (AL) was 29.10± 0.59 mm, and the logarithm of the minimum angle of resolution best corrected visual acuity (logMAR BCVA) was 2.23±0.57. Patients previously received pars plana vitrectomy (PPV) combined with internal limiting membrane stripping surgery, which was more than 1 time. All eyes underwent standard pars plana three-channel 23G PPV combined with amniotic membrane covering and silicone oil filling. The silicone oil was removed 6 months after surgery. Follow-up time was up to 3 months after silicone oil removal surgery. 1, 3, and 6 months after the operation, the same equipment and methods were used to conduct relevant examinations before the operation to observe the closure of the macular hole, retinal reattachment and changes in logMAR BCVA. The logMAR BCVA before and after surgery was compared by paired t test. Results:At 1, 3, and 6 months after the operation, the retinas of all eyes were anatomically repositioned, the macular holes were well closed, and the amniotic membrane was attached to the retina. At 3 months after the silicone oil removal operation, there was no recurrence of macular hole in all eyes; logMAR BCVA was 1.35±0.32. No serious complications occurred during and after surgery in all eyes.Conclusion:Amniotic membrane patching is a safe and effective method for recurrent macular hole associated with MHRD.

Objective:Regulatory quantitative trait loci (regQTL) theory can help to evaluate the regulation function of single nucleotide polymorphisms (SNPs) on crucial biological signals from a three-dimensional perspective. The aim of this study was to investigate the effect of these regQTL-SNPs on the susceptibility of lung cancer.Methods:Based on the regQTL theory, using the database of identified lung cancer regQTL-SNPs, we screened the SNPs that may function as regQTL in the reported susceptible regions of lung cancer by genome-wide association study(GWAS), and a two-stage case-control study was conducted (screening stage: 2 331 lung cancer cases and 3 077 healthy controls; validation stage: 626 lung cancer cases and 667 healthy controls) to definite the association of related regQTL-SNPs with the susceptibility of lung cancer.Results:A total of 8 regQTL-SNPs were screened in the reported susceptible regions of lung cancer by GWAS. Among which, 3 SNPs were significantly associated with the risk of lung cancer ( P<0.05) in the screening stage. Further validation results indicated that the variant T allele of rs6998591 in ADRA1A was significantly associated with increased risk of lung cancer (additive model: OR=1.33, 95% CI:1.01-1.74, P=0.040). In addition, the variant G allele of rs11202916 in ACTA2 was significantly associated with decreased risk of lung cancer (recessive model: OR=0.71, 95% CI:0.52-0.96, P=0.026). Stratified analysis indicated that the variant T allele of rs6998591 significantly increased lung squamous cell carcinoma risk (additive model: OR=1.53, 95% CI: 1.01-2.32, P=0.043), while the variant G allele of rs11202916 significantly decreased lung adenocarcinoma risk (additive model: OR=0.83, 95% CI: 0.69-0.98, P=0.031). Gene-environment interaction analysis indicated that the risk of developing lung cancer increased by 235% in smoking individuals carrying rs6998591 variant T allele compared with those non-smoking individuals carrying no rs6998591 variant T allele( OR=3.35,95% CI:2.10-5.34, P<0.001). Conclusion:There are two regQTL-SNPs that could significantly affect the susceptibility of lung cancer in the GWAS reported susceptible regions of lung cancer.

The Zika virus (ZIKV) and dengue virus (DENV) flaviviruses exhibit similar replicative processes but have distinct clinical outcomes. A systematic understanding of virus–host protein–pro-tein interaction networks can reveal cellular pathways critical to viral replication and disease patho-genesis. Here we employed three independent systems biology approaches toward this goal. First, protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and 20,240 human proteins revealed multiple conserved cellular pathways and protein complexes, including proteasome complexes. Second, an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process. Third, high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds, including six proteasome inhibitors that suppress both ZIKV and DENV replication. Integrative analyses of these orthogonal datasets pinpoint proteasomes as crit-ical host machinery for ZIKV/DENV replication. Our study provides multi-omics datasets for fur-ther studies of flavivirus–host interactions, disease pathogenesis, and new drug targets.

Objective:To discuss the effects of recombinant IFN-α-IL-18 fusion protein on chicken lymphocyte histamine induced and the NF-κB p65 activation and nucleo-cytoplasmic transport.Methods: The healthy chickens blood was sterile adopted with anticoagulant,then separation of the chicken peripheral blood lymphocyte and divided into 10 groups:The yeast expression and purification protein IFN-α-IL-18,IL-18,IFN-α were added with 250 ng/ml,500 ng/ml and 1 000 ng/ml respectively while the control was only added RPMI1640 with 3 repetitions for each group.Then the histidine decarboxylase activity,histamine,IFN-γ,PI3K,MAPK and NF-κB p65 in cell nucleus were detected.Results: The recombinant IFN-α-IL-18 and IL-18 could significantly promote the activity of histidine decarboxylase (P<0.01),increase the contents of histamine (P<0.01),induce IFN-γ (P<0.01),improve the contents of PI3K (P<0.01) and the NF-κB p65 levels in nucleus (P<0.01),and the higher concentration of IFN-α had a similar effect to lymphocytes.The effects of IFN-α-IL-18,IL-18 and IFN-α on MAPK was acratia.Conclusion: IFN-α-IL-18 and IL-18 can stimulate chicken peripheral blood lymphocyte populations increased histamine contents significantly and promote the induction of IFN-γ.IFN-α-IL-18,IL-18 and IFN-α increase PI3K expression in lymphocyte associated with the NF-κB activation and NF-κB p65 nucleo-cytoplasmic transport.The study built foundation for the function of IFN-α-IL-18 and the exploration of the mechanism of controlling epidemic diseases.

DNA methylation is an important epigenetic modification mode , which plays a crucial role in gene expression , genome stability and development .DNA methylation is catalyzed and maintained in cell proliferation by the family of DNA methyltransferases.The ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC).Here, we briefly describe the TET enzymes and their role in cancer , and the distribution , the role and detection method of those three oxidation products of cytosine in genome .