[Genome sequence analysis of two SARS-CoV-2 virus infections in Inner Mongolia, 2022].

The target gene sequences of the novel coronaviruses obtained by sequencing were compared with the reference sequences to analyze the genetic variation of the two cases of the novel coronaviruses from Inner Mongolia Autonomous Region in 2022 and to explore the sources of infection. The results showed that the two sequences belonged to different evolutionary branches, Delta (AY.122) and Omicron (BA.1.1), respectively. hCoV-19/Inner Mongolia/IVDC-591/2022 had 48 single nucleotide polymorphisms on the genome sequences, sharing 40 nucleotide mutation sites with a Mongolian strain; hCoV-19/Inner Mongolia/IVDC-592/2022 genome shared 57 nucleotide mutation sites with a UK strain, and the nucleotide mutation site identity was 100% (57/57). Phylogenetic analysis showed that the target gene sequences were not directly related to domestic novel coronavirus sequences during the same period, but were related to isolates from Europe and Mongolia.

Utilizing a novel hybrid brachytherapy technique FINITO (Freehand Interstitial Needles in addition to Tandem and Ovoid) for locally advanced cervical cancer.

PURPOSE: We aimed to assess the clinical feasibility and advantages of using a novel hybrid brachytherapy technique by placing Freehand Interstitial Needles in addition to the Tandem and Ovoid applicator (FINITO) for the treatment of locally advanced cervical cancer (LAC). METHODS AND MATERIALS: A retrospective analysis was performed on two cohorts of patients with LACC treated at our institution: 29 patients in the FINITO group and 17 patients in the control group using T&O only approach. Clinical outcomes of interest included local control (LC), progression-free survival (PFS), overall survival (OS), and rates of acute and late toxicities. Kaplan-Meier methodology was used to estimate OS, PFS, and LC. Wilcoxon signed-rank test was used to compare the median values for dosimetry parameters. A p-value of ≤ 0.05 was considered statistically significant. All statistical analyses were performed using RStudio. RESULTS: At a median of 2 years there was no difference in rates of OS, PFS or LC between the FINITO and the control group of patients. The 2-year OS, PFS, and LC for the FINITO group were 59% (95% CI 34%-100%), 58% (95% CI 38%-89%), and 84% (95% CI 69%-100%), respectively. Late toxicities were significantly lower in the FINITO group for both gastrointestinal and genitourinary symptoms (p = 0.001 and 0.01, respectively) as compared to the T&O group. CONCLUSION: Based on the equivalent LC rate and lower toxicity profile, our FINITO technique appears to be an excellent alternative to the standard intracavitary brachytherapy in patients with advanced disease, especially in resource-limited settings.

[Two novel and de novo KMT2D mutations on the same allele cause Kabuki syndrome].

Objective: To screen the candidate genes in a patient with Kabuki syndrome (KS), providing basis for genetic counseling, prenatal screening, prenatal diagnosis and facilitating early treatment. Methods: This study included a 16-year-old female KS patient born of non-consanguineous Chinese parents who presented to Department of Orthognathic & Cleft Lip and Palate Plastic Surgery, School and Hospital of Stomatology, Wuhan University. Genomic DNA was extracted from the peripheral blood of the subjects and analyzed by whole-exome sequencing (WES). Sanger sequencing was performed to validate the mutation in the candidate gene. The conformational and physicochemical changes of the mutant were analyzed by Alphafold2, Antheprot and DOG.2.0.1, respectively. Distribution of KMT2D mutations in patients with KS was analyzed based on the Human Gene Mutation Database Results: The proband manifested a typical KS facial gestalt, congenital cleft palate, fifth finger deformity, hypodontia, renal hypoplasia and hydronephrosis. Two de novo mutations c.[1166A>C; 1167dupC] (NM_003482) in cis on the same allele in the KMT2D gene were identified by WES and confirmed by allele-specific PCR. Bioinformatics analysis showed that three more α-helixes were added, and a (ß-) turn and a (ß-) sheet were reduced in KMT2D p. Y389S, p.V390Rfs*26 compared with the wild type. Meanwhile, the interceptive mutant-KMT2D protein p.V390Rfs*26 lost all four domains (FYRN domain, FYRC domain, SET domain, and PostSET domain), which may cause functional disabilities. Conclusions: Our study is the first to identify two novel and de novo KMT2D mutations in cis on the same allele in a KS patient and extends the KMT2D mutation spectrum of KS, providing evidence for genetic susceptibility counseling, prenatal screening and diagnosis, and early treatment of KS.

[The role of Müller cells in the formation and development of macular hole].

Müller cells are important glial cells in the retina, which play important roles in maintaining the stability of the retina by mechanical support, homeostasis, and physiological metabolism, as well as protecting photoreceptor cells and retinal pigment epithelial cells. The degeneration and destruction of Müller cells are often accompanied by various retinal diseases, and the function of Müller cells is changed under pathological conditions. Based on the summary of the morphology, distribution and function of Müller cells, this article analyzes the different manifestations and changes of Müller cells in different stages of macular hole and the closely related mechanisms, aiming to clarify the role of Müller cells in the formation and development of macular hole and to provide reference for the prediction of disease progression and guidance of treatment.(This article was published ahead of print on the official website of Chinese Journal of Ophthalmology on Augest 28, 2023).

[Comparison of pingyangmycin fibrin glue composite and pingyangmycin dexamethasone composite in the treatment of pharyngolaryngeal venous malformation].

Objective: To analyze and compare the efficacy and safety of pingyangmycin fibrin glue composite (PFG) and pingyangmycin dexamethasone composite (PD) in the treatment of pharyngolaryngeal venous malformation (VM). Methods: The clinical data of 98 patients with pharyngolaryngeal VM who underwent sclerotherapy with pingyangmycin composite in the First Affiliated Hospital of Sun Yat-sen University from June 2013 to November 2022 were retrospectively analyzed. According to their treatment, patients were divided into PFG group (n=34) and PD group (n=64), among those patients there were 54 males and 44 females, aged 1-77(37.06±18.86)years. The lesion size, total treatment times and adverse events were recorded before and after treatment. And the efficacy was divided into three grades: recovery, effective and invalid. According to the length of VM, all patients were divided into three subgroups, to compare the differences in efficacy and treatment times between each two groups.And finally the adverse events and their treatments were analyzed. SPSS 25.0 software was used for statistical analysis. Results: The efficacy of PFG group was 94.11%(32/34), the recovery rate was 85.29%(29/34).And the efficacy of PD group was 93.75%(60/64), the recovery rate was 64.06%(41/64). No serious adverse eventst occurred in subgroup comparison, there was no statistical difference between the two groups in efficacy and the times of treatments when the length was≤3 cm (Zefficacy=1.04, ttreatment times=2.18, P>0.05); when the length was 3-5 cm, there was no significant efficacy difference between the two groups(Zefficacy=1.17, P>0.05), but the treatment times of PFG were less (ttreatment times=4.87, P<0.01); when the length≥5 cm, efficacy of PFG was significantly better than PD (Zefficacy=2.94, P<0.01), and had fewer treatments times (ttreatment times=2.16, P<0.01). There were no serious adverse events in either group during treatment and follow-up. Conclusion: Both PFG and PD are safe and effective composite sclerotherapy agent for the treatment of laryngeal VM, but PFG has a higher cure rate and fewer treatment times for massive lesions.

[Autophagy regulates multiple organ injury in obstructive sleep apnea and its related mechanisms].

Obstructive sleep apnea is a sleep-related hypoxia/reoxygenation syndrome that can lead to cardiovascular and cerebrovascular diseases, glucose and lipid metabolism, nervous system and even multiple organ damage, and is a serious threat to human health. Autophagy is a process by which eukaryotic cells rely on the lysosome pathway to degrade abnormal proteins and organelles, maintain homeostasis of intracellular environment and achieve self-renewal. Many studies have found that obstructive sleep apnea causes damage to myocardial, hippocampus, kidney and other organs, and its mechanism may be related to autophagy.

The effect of driving pressure-guided ventilation strategy on the patients with mechanical ventilation: a meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this study was to evaluate the effect of driving pressure (DP) guided ventilation strategy on the patients with mechanical ventilation in the hospital. MATERIALS AND METHODS: The articles published in PubMed, the Cochrane Library, the China National Knowledge Information (CNKI), Wei Pu, Wan Fang database and Web of Science from inception to September 2021 were retrieved. The Q test and the I² statistic were used to assess statistical heterogeneity. Risks ratios (RR) with 95% confidence intervals (CI) were calculated for mortality. RESULTS: Seven studies (n=1,405 patients) were included. Five studies reported an adjusted Risk Ratio (RR) of mortality. Compared with the control group, the DP guided ventilation group was associated with a decreased mortality (RR 0.56; 95% confidence interval [CI], 0.39-0.79; p=0.001; I2 = 23%) using a fixed-effects model without significant heterogeneity. The control group had significantly higher driving pressure level than DP guided group (MD -3.03, 95%CI, -5.72 - -0.34, I2=100%, p=0.03); PaO2/FiO2 was significantly higher in DP guided group than in control group (MD 43.37; 95%CI, 12.58-74.15; I2=97%, p=0.006). There was no statistically significant difference in respiratory compliance, complications, platform pressure, duration of mechanical ventilation and the length of hospital stay between the DP guided group and the control group. CONCLUSIONS: The results suggested that the driving pressure guided ventilation strategy could decrease the mortality and increase oxygenation index (OI). However, further high-quality randomized controlled trials (RCTs) are needed to verify the impact of driving pressure on mechanically ventilated patients.

[Mechanism of cleft palate in C57BL/6N mice induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin].

Objective: To explore the molecular mechanism of cleft palate in mice induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). Methods: The pregnant mice were randomly divided into TCDD-treated group (n=42) and control group (n=42). TCDD-treated group was given by gavage a single dose of TCDD (64 µg/kg) at 8: 00 AM on gestation day 10 (GD10) and the control group was given by gavage the isopyknic corn oil. At GD13-GD15, the fetal mice palate development was observed by HE staining. The mouse embryonic palatal mesenchymal cell proliferation was detected by 5-bromo-2-deoxyuridine (BrdU) immunofluorescence. The localization and expression of maternally expressed gene3 (MEG3) in mouse embryonic palatal mesenchymal cells was detected by situ hybridization and real-time PCR (RT-PCR). The key protein expressions of transforming growth factor-ß (TGF-ß)/Smad signaling pathway in mouse embryonic palatal mesenchyme were analyzed by Western blotting. The interaction of MEG3 and TGF-ß receptor Ⅰ (TGF-ßRⅠ) was examined by RNA binding protein immunoprecipitation (RIP). Results: At GD13 and GD14, compared with the control group, the ratio of BrdU-positive cells in the palatal mesenchyme of TCDD-treated fetuses decreased significantly (GD13, t=6.66, P=0.003; GD14, t=6.56, P=0.003). However, at GD15, the ratio of BrdU-positive cells was significantly increased (t=-5.98, P=0.004). MEG3 was mainly expressed in the nuclei of fetal mouse palatal mesenchymal cells, and the expression of MEG3 in TCDD group was significantly increased at GD13, GD14 and GD15(GD13, t=39.28, P=0.012; GD14, t=18.75, P=0.042; GD15, t=28.36, P=0.045). At GD14, TCDD decreased the levels of p-Smad2 and Smad4 in embryonic palate mesenchymal cells (p-Smad2, t=9.48, P=0.001;Smad4, t=63.10, P=0.001), whereas the expression of Smad7 was significantly increased at GD14 (t=30.77, P<0.001). The results of the RIP experiment showed that the amount of TGF-ßRⅠ-bound MEG3 in mouse embryonic palatal mesenchymal cells in the TCDD group (23.940±1.301) was higher than that in the control group (8.537±1.523)(t=24.55, P<0.001). Conclusions: MEG3 is involved in the suppression of mouse embryonic palatal mesenchymal cell proliferation, functioning at least in part via interacting with the TGF-ßRⅠ protein and thereby suppressing Smad signaling in the context of TCDD induced cleft palate.

[Study on mental health status of pregnant women and its influencing factors in the third trimester].

Objective: To understand the mental health status of pregnant women in the third trimester of pregnancy, and explore the influencing factors. Methods: The general demographic information and pregnancy information of 575 pregnant women in the Chinese Pregnant Women Cohort Study were collected. The mental health status of pregnant women in the third trimester was investigated by using Edinburgh Postpartum Depression Scale, Self-Rating Anxiety Scale and University of California at Los Angeles. Multivariate unconditional logistic regression was used to analyze the influencing factors for mental health of pregnant women. Results: In the third trimester of pregnancy, the incidence of depression was 16.52%, the incidence of anxiety was 11.13%, and the incidence of feeling loneliness was 26.26%. Logistic regression analysis showed that compared with those with education level of junior high school below, those with education level of college or bachelor's degree (OR=0.418, 95%CI: 0.184-0.950) and master's degree or above (OR=0.116, 95%CI: 0.027-0.503) were less likely to feel loneliness. Pregnant women with higher annual family income (10 000 RMB yuan) were less likely to suffer from depression (≥20 vs. <10: OR=0.527, 95%CI: 0.279-0.998), anxiety (10-20 vs. <10: OR=0.363, 95%CI: 0.180-0.731; ≥20 vs. <10: OR=0.271, 95%CI: 0.132-0.554) and feeling loneliness (≥20 vs. <10: OR=0.477, 95%CI: 0.276-0.826). Conclusions: The education level and family income have impacts on the mental health status of pregnant women in the third trimester. Medical staff should give targeted psychological advice to pregnant women to improve their mental health status.

[Brief introduction of population medicine and value-based healthcare].

Three healthcare revolutions and four medical paradigm shifts have had a profound impact on the development of healthcare system, which has greatly improved human health, however, the COVID-19 pandemic has exposed hidden dangers and problems in the construction of the healthcare system. In this paper, we made a brief introduction of population medicine and value-based healthcare for the purpose of suggesting new ideas and directions for the future development of healthcare system.

[Data standard and data sharing in clinical cohort studies].

Data standard plays an important role in the process of data collection, Integration and sharing in clinical cohort studies, and more attention have been paid to it. This paper summarizes the 5 international proven data standard model, analyze their characteristics and development status, and match their data modules with the general data set of the clinical cohorts to evaluate the international data standard models' applicability and provide reference for the development and improvement of the data standard model for clinical cohort studies in China.

[Application of AGREEâ ¡ in evaluating quality of esophageal cancer screening practice guidelines].

High-quality clinical practice guidelines are of great significance for standardizing the clinical diagnosis and treatment process and improving the overall quality of health care. The Appraisal of Guidelines for Research & Evaluation InstrumentⅡ (AGREEⅡ) is one of the recognized tools for the evaluation of the quality of clinical practice guidelines. It has been translated into Chinese and is widely used in guideline formulation and quality evaluation. This article intends to take the comparatively high-quality clinical practice guidelines in the field of esophageal cancer screening in China, i.e. "Expert Consensus on Early Esophageal Cancer and Precancerous Lesion Screening in China (2019, Xinxiang)" as an example, to interpret the use of AGREEⅡ item by item, which might provide a reference for medical and health workers to better understand and use the assessment tool.

[Study on the operation process and construction standard of an esophageal cancer screening cohort study].

One of the most cost-effective measures in cancer prevention on cancer is to advocate to be aware of the disease, consciously changing negative behaviors, and taking the initiative to participate in regular physical checkup programs. Esophageal cancer is one of the malignant tumors accompanied by a heavy disease burden in China. Routine screening, early diagnosis, and treatment are the critical points of preventing and treating the disease. Cohort studies help understand the natural history and risk factors of esophageal cancer and identify high-risk groups of the disease. This paper intends to discuss the construction specifications of the multi-dimensional dynamic follow-up shared cohort for esophageal cancer by studying the risk factors, monitoring, and collecting biological sample information, providing references for developing a standardized and unified screening cohort research procedure, and necessary standards on esophageal cancer in the future.

Electrochemical Determination of Levodopa Using Zinc Sulfide Nanospheres-Reduced Graphene Oxide.

Zinc sulfide nanospheres (ZnS NSs) were prepared by hydrothermal synthesis and graphene oxide (GO) was prepared by the Hummer's method. ZnS NSs-rGO/ITO electrode was synthesized by heat treatment at a certain temperature, which was used for the detailed electrochemical determination of levodopa (LD). Finally, they were annealed to form the ZnS NSs-rGO/ITO electrode for detecting levodopa (LD). The results reveal that the ZnS NSs with the diameter of ~1 µm are covered by rGO. The ZnS NSs-rGO/ITO electrode has a good sensitivity of 1.43 µA µM -1 for the determination of LD in the concentration range of 1-40 µM. Moreover, it also shows a good selectivity, reproducibility and stability. In order to verify the practicability, we also use the electrode to detect LD in human serum. The detection results also prove that the electrode can be used in real life.

[Quality assessment of global lung cancer screening guidelines and consensus].

Objective: To understand the research progress and quality of lung cancer screening guidelines and consensus in China and abroad, and to provide reference for the formulation of high-quality lung cancer screening guidelines in China. Methods: Databases including PubMed, Medline, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, SinoMed, VIP and Wanfang Data were searched, websites and important references were also searched by hand retrieval. The Appraisal of Guidelines for Research & Evaluation Ⅱ(AGREE Ⅱ) and Reporting Items for Practice Guidelines in Healthcare (RIGHT) were used to assess the quality of newly published or updated guidelines and consensus. Results: A total of 9 guidelines and consensus published between 2015 and 2020 were included in this study, with countries including the United States, China, Canada, Saudi Arabia and South Africa. The field of scope and purpose and clarity of presentation scored relatively high but the rigor of development and applicability scored low. Five guidelines were judged to be A-level, all of which were published abroad, and the remaining four were B-level, including three guidelines and consensus issued by China and 1 guideline issued by South Africa. The report rate of RIGHT were higher in basic information and background, lower in review and quality assurance, funding and declaration and management of interests. There were 5 guidelines with a good level and 4 guidelines and consensus with a moderate level. The best overall quality guidelines were those published by the American College of Chest Physicians in 2018 and by the Canadian Task Force on Preventive Health Care in 2016. Conclusions: The number of countries and institutions that issue lung cancer screening guidelines and consensus had been increasing gradually, but the quality in China remained low. It is necessary to develop high-quality lung cancer screening guidelines suitable for China's national conditions in combination with evidence-based methods to guide practice.

Keratinocytes: innate immune cells in atopic dermatitis.

The skin is a unique immune organ that constitutes a complex network of physical, chemical and microbiological barriers against external insults. Keratinocytes are the most abundant cell type in the epidermis. These cells form the physical skin barrier and represent the first line of the host defense system by sensing pathogens via innate immune receptors, initiating anti-microbial responses and producing various cytokines, chemokines and anti-microbial peptides, which are important events in immunity. A damaged epidermal barrier in atopic dermatitis allows the penetration of potential allergens and pathogens to activate keratinocytes. Among the dysregulation of immune responses in atopic dermatitis, activated keratinocytes play a role in several biological processes that contribute to the pathogenesis of atopic dermatitis. In this review, we summarize the current understanding of the innate immune functions of keratinocytes in the pathogenesis of atopic dermatitis, with a special emphasis on skin-derived anti-microbial peptides and atopic dermatitis-related cytokines and chemokines in keratinocytes. An improved understanding of the innate immunity mediated by keratinocytes can provide helpful insight into the pathophysiological processes of atopic dermatitis and support new therapeutic efforts.