Analysis of ocular biometric parameters in Tibetan patients with age-related cataract / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To compare the differences of ocular biometric parameters of age-related cataract between Tibetan and Han ethnic groups, and to analyze the distribution characteristics of ocular biometric parameters in Tibetan cataract patients.METHODS:Retrospective cohort study. A total of 661 patients(1 030 eyes)with age-related cataract confirmed in the hospital between January 2019 and December 2020 were enrolled. The parameters of axial length, anterior chamber depth, keratometry, corneal astigmatism and astigmatic axis were measured by IOL Master 500 in 483 cases(739 eyes)of Tibetan age-related cataract patients and 178 cases(291 eyes)of Han patients.RESULTS:The axial length, anterior chamber depth and corneal astigmatism of the Tibetan patients with age-related cataract were 23.33(22.81, 23.86)mm, 3.04(2.79, 3.30)mm and 0.73(0.47, 1.07)D. The mean keratometry was 43.89±1.35 D. The results indicated that Tibetan cataract patients had shorter axial lengths and smaller keratometry compared to Han patients(all P<0.05). Age in Tibetan patients was negatively correlated with axial length and anterior chamber depth, and positively correlated with keratometry(all P<0.05). Tibetan male patients had longer axial lengths, deeper anterior chambers, and flatter corneas compared to female patients(all P<0.05).CONCLUSION:There were differences in ocular biometric parameters between age-related cataract patients of Tibetan and Han ethnicities. The distribution of ocular biometric parameters in Tibetan cataract patients varied across different age groups and gender groups.

Association of diabetic retinopathy with anxiety and depression / 国际眼科杂志(Guoji Yanke Zazhi)

As society advances and living standards improve, there is a growing emphasis on the impact of mental health on illness and the interaction between them. Diabetes mellitus is one of the most common underlying diseases, and it is often accompanied by depression and anxiety. There are also many complications of diabetes, such as diabetic retinopathy(DR). DR is the leading cause of vision loss in diabetes. Vision loss inevitably increases anxiety and/or depression, which in turn may directly or indirectly affect the treatment or progression of patients with DR. This article reviews how to determine the anxiety and depression status of patients with DR, related assessment tools and methods, and their interaction with the treatment of DR. The interaction of anxiety-depressive states with DR treatment was also discussed. This review aims to raise awareness of the mental health of patients with DR, enhance doctor-patient communication and build doctor-patient trust, thus enhancing treatment adherence and clinical efficacy for individuals with DR and helping them to improve the quality of life.

Effect of cognitively engaging physical activity on developing executive function of children and adolescents: a systematic review based on ICF / 中国康复理论与实践

ObjectiveTo systematically review the intervention effect of cognitively engaging physical activity (CEPA) on executive function of children and adolescents. MethodsLiteratures in Chinese and English were retrieved from databases of Web of Science, PubMed, Medline, EBSCO and CNKI, from the establishment to November 30th, 2023. According to the inclusion and exclusion criteria, the literatures that met the requirements were screened, and their quality was evaluated and systematically reviewed. ResultsA total of 15 literatures were included, published between 2014 and 2023, from eight countries, involving 1 806 subjects aged four to 16 years. The average score of PEDro scale was 6.6. The intensity of the CEPA intervention ranged from 64% to 93% HRmax, the duration of a single session ranged from ten to 60 minutes, and the frequency of the intervention was two to five sessions a week, for four to 24 weeks. Specific forms of CEPA included football, basketball and floorball combined with cognitive tasks; running, jumping, squatting, sitting, spinning and balancing combined with cognitive tasks; and exergaming combined with cognitive tasks. Eleven researches showed positive effects of CEPA intervention on at least one component of executive function. However, six of the seven researches involving working memory failed to verify the positive effects. Twelve researches compared the intervention effects of CEPA and rutine exercise or regular physical education classes, and nine researches found that CEPA was more effective on executive function. ConclusionThe CEPA is effective on the executive function of children and adolescents, specifically on cognitive flexibility; it shows inconsistent effects on inhibitory control, and its effect on working memory has not been verified. The intervention types of CEPA are divided into ball games combined with cognitive tasks, basic motor skills training combined with cognitive tasks, and exergaming combined with cognitive tasks.

Chronic hepatitis B virus infection and metabolic associated fatty liver disease： The known and unknown aspects / 临床肝胆病杂志

Chronic hepatitis B virus （HBV） infection is the main cause of the disease burden of viral hepatitis worldwide， and meanwhile， due to changes in lifestyle and dietary habits， the incidence rate of metabolic associated fatty liver disease （MAFLD） is constantly increasing， making MAFLD the leading chronic liver disease around the world. Chronic HBV infection comorbid with MAFLD is becoming more and more common in clinical practice. Metabolic factors， rather than viral factors， are the main cause of chronic HBV infection comorbid with MAFLD. During disease progression， steatohepatitis and fibrosis， rather than steatosis， are the main influencing factors for the progression to liver cirrhosis and hepatocellular carcinoma. For patients with chronic HBV infection and MAFLD， integrated management of virus and metabolic factors is of great importance. This article reviews the tissues regarding the interaction， prognosis， and clinical management of chronic HBV infection and MAFLD.

Thoughts on Ethical Collaborative Review and Management of Multi-center Clinical Research / 中国医学伦理学

For multi-center clinical research, how to ensure the quality of ethical review and improve the efficiency of ethical review through cooperation among centers is an important direction for clinical research management departments and research parties to explore. By combing and analyzing the existing pattern of multi-center ethical review at home and abroad, combining the current situation of the ethical review and management development in China, taking cancer clinical research as the breakthrough point, it was advocated to establish a cooperative review led by professional institute in domestic, on the basis of extensive and in-depth training exchanges and effective communication on the same platform, collaborative review, ensure quality and efficiency, so as to promote and implement the "mutual recognition" of ethical review. Then, this paper further put forward the concept of "whole-process linkage" in the ethical management process of multi-center clinical research, and pointed out that all research parties should clarify their responsibilities, enhance their awareness and ability, and jointly and comprehensively implement the protection of subjects among clinical researchers.

Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumors: a report of 15 cases in a national medical center / 中华妇产科杂志

Objective: To evaluate the incidence, treatment, and survival outcomes of Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumor (MGCT-NDG). Methods: A retrospective study was performed on Swyer syndrome patients with MGCT-NDG between January 2011 and December 2022 in Peking Union Medical College Hospital to investigate their characteristics and outcomes. Results: A total of 15 patients (4.9%, 15/307) with Swyer syndrome were identified in 307 MGCT-NDG patients. The average age at diagnosis of MGCT-NDG and Swyer syndrome were (16.8±6.7) and (16.7±6.6) years, respectively. Six cases were preoperatively diagnosed as Swyer syndrome, of which 4 cases received bilateral gonadectomy with or without hysterectomy, while the other 2 cases underwent removal of gonadal tumor and unilateral gonadectomy with hysterectomy, respectively. Of the 9 patients postoperatively diagnosed as Swyer syndrome, unilateral gonadectomy, removal of gonadal tumor, and unilateral gonadectomy with hysterectomy were performed in 6 patients, 2 patients, and 1 patient, respectively. Mixed malignant germ cell tumor (MGCT;10 cases), yolk sac tumor (4 cases), and immature teratoma (1 case) were the pathological subtypes, in the descending order. There were International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ in 6 cases, stage Ⅱ in 3 cases, stage Ⅲ in 5 cases, and stage Ⅳ in 1 case, respectively. Eleven patients received reoperation for residual gonadectomy after a average delay of (7.9±6.2) months, including 8 MGCT-NDG patients and 1 gonadoblastoma patient, no tumor involved was seen in the remaining gonads in the other 2 cases. Ten patients experienced at least one recurrence, with a median event free survival of 9 months (5, 30 months), of which 2 patients received surgery only at the time of initial treatment. All patients with recurrence received surgery and combined with postoperative chemotherapy. After a median follow-up of 25 months (15, 42 months), 10 patients were disease-free, 3 patients died of the tumor, 1 died of side effects of leukemia chemotherapy, and 1 survived with disease. Conclusion: The incidence rate of Swyer syndrome in patients with MGCT-NDG is about 4.9%; timely diagnosis and bilateral gonadectomy should be emphasized to reduce the risk of reoperation and second carcinogenesis in this population.

Phosphatidic acid-enabled MKL1 contributes to liver regeneration: Translational implication in liver failure

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis / 中华医学杂志(英文版)

BACKGROUND@#Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 ( CTNNB1 ), the most frequently altered proto-oncogene in hepatic neoplasms.@*METHODS@#Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 ( β-catenin Δ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-catenin Δ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro . Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus ( HBV ); β-catenin lox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer.@*RESULTS@#MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV ; β-catenin lox(ex3)/+ mice, which stimulated concurrent Ctnnb1- activated mutation and HBV infection in liver cancer.@*CONCLUSION@#MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.

Prenatal diagnosis and outcome of pregnancy for women with high risks by screening of fetal free DNA from peripheral blood samples / 中华医学遗传学杂志

OBJECTIVE@#To analyze the results of prenatal diagnosis and outcome of pregnancy for women with a high risk for fetal aneuploidies.@*METHODS@#A total of 747 cases of prenatal diagnosis by amniocentesis due to high risks by non-invasive prenatal testing (NIPT) were selected from January 2015 to March 2022 in the Drum Tower Hospital Affiliated to Nanjing University Medical School. The amniotic fluid samples were subjected to chromosomal karyotyping and/or chromosomal microarray analysis. All cases were followed up by searching the birth information or telephone calls, and the results were recorded. 2 test or F test were used for comparing the difference between the groups.@*RESULTS@#Among the 747 pregnant women with a high risk by NIPT, 387 were true positives, and the overall positive predictive value (PPV) was 51.81%. The PPVs for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13) and sex chromosome aneuploidies (SCA) were 80.24% (199/248), 60% (48/80), 14% (7/50) and 38.97% (106/272), respectively. The PPV for T21 was significantly higher than T18 and T13 (χ2 = 85.216, P < 0.0001). The PPV for other chromosomal aneuploidies and copy number variations (CNVs) were 11.11% (5/45) and 40.74% (22/52), respectively. The PPV for increased X chromosomes was significantly higher than X chromosome decreases (64.29% vs. 22.22%, χ2 = 5.530, P < 0.05). The overall PPV for elder women (≥ 35 years old) was significantly higher than younger women (69.35% vs. 42.39%, χ2 = 49.440, P < 0.0001). For T21 and T18, the PPV of Z ≥ 10 group was significantly higher than that for 3 ≤ Z < 5 group or 5 ≤ Z < 10 group (P < 0.05). Among 52 cases with a high risk for CNVs, the PPV for the ≤ 5 Mb group was significantly higher than the 5 Mb < CNVs < 10 Mb or > 10 Mb groups (60% vs. 30%60% vs. 23.53%, P < 0.05). Among the 387 true positive cases, 322 had opted for induced labor, 53 had delivered with no abnormal growth and development, and 12 were lost during the follow-up.@*CONCLUSION@#The PPVs for common chromosomal aneuploidies are related to the age and Z value of the pregnant women, which were higher in the elder group and higher Z value group. In addition, the PPV is associated with high risk types. The PPV for T21 was higher than T18 and T13, and that for 45,X was lower than 47,XXX, 47,XYY or 47,XXY syndrome. NIPT therefore has relatively high PPVs for the identification of chromosomal CNVs.

Formation of Hyperprogression of Immunotherapy from Perspective of "Yang Deficiency and Toxin Knot" and Role of "Five Views on Differentiation and Treatment" Intervention / 中国实验方剂学杂志

Immune checkpoint inhibitors （ICIs） have shown good efficacy in tumor treatment and have changed the landscape of tumor treatment. However， some patients treated with ICIs have not only failed to achieve the desired therapeutic effect， but also developed an atypical response pattern of abnormally accelerated tumor growth， namely hyperprogressive disease （HPD）. The pathogenesis of HPD is still unclear and it is difficult to diagnose， which poses a challenge for clinical identification and treatment decisions. Exploring the underlying mechanism of HPD is important to improve the effect of immunotherapy. Based on the theory of "Yang deficiency and toxic knot"， this paper discussed the mechanism of HPD in immunotherapy from the perspective of "spleen and kidney Yang deficiency and hefty toxic pathogens". It was concluded that the inactivation of p53 oncogene and immunosuppressive microenvironment were the manifestations of the deficiency of healthy qi in the body and declined yang in the spleen and kidney， serving as an important basis for the occurrence of HPD. Adverse reactions caused by ICIs belong to the category of "drug toxicity". The occurrence and development of murine double minute 2 （MDM2）/murine double minute 4 （MDM4） activation， epidermal growth factor receptor （EGFR） mutation， and tumor inflammatory microenvironment are the manifestations of the hyperactivity of pathogenic Qi， conflict of cancer toxicity and drug toxicity， and being hefty by virtue of deficiency， which can promote the abnormal proliferation of tumor cells， and they are the core pathogenic elements of HPD and are closely related to disease prognosis. In terms of treatment， under the guidance of the theory of "five views on differentiation and treatment" （time-space view， core view， symptom view， precision view， and disease-before-onset view）， which was summarized according to the clinical practice of this research team， this paper， taking the prevention and treatment of HPD as the entry point， formulated traditional Chinese medicine （TCM） compounds to reinforce healthy Qi and warm Yang and realize the dynamic management of the whole spatiotemporal cycle， and removed toxins and resisted cancer to realize the all-round systemic intervention of the specimen. Additionally， targets were enriched in the macro-clinical manifestations and microscopic pathological changes of HPD to improve the targeting of drug selection and the precision of prevention and treatment， giving full play to the unique therapeutic advantages of TCM， and providing new ideas for the clinical application of TCM in the prevention and treatment of HPD.

Mechanism of microRNA-30d-5p regulating osteogenic differentiation of bone marrow stromal cells through glucose-regulated 78 / 解剖学报

Objective To investigate the effect of microRNA(miR)-30d-5p on osteogenic differentiation and apoptosis of bone marrow stromal cells and its mechanism. Methods Bone marrow stromal cells were divided into miR-30d-5p overexpression negative control group, miR-30d-5p overexpression group, miR-30d-5p inhibition negative control group and miR-30d-5p inhibition group. Alkaline phosphatase (ALP) staining was used to identify osteogenesis, alizarin red staining was used to detect calcium nodules precipitation, and TUNEL was used to detect apoptosis. mRNA and protein expression levels were detected by Real-time PCR and Western blotting, and the potential binding sites of miR-30d-5p were predicted by the bioinformatics analysis website Targetscan 7.1. Results After miR-30d-5p overexpression, osteogenic differentiation ability, and mineralization ability of the cells decreased (P<0.05), while apoptosis level increased (P< 0.05). The expression of glucoregulatory protein 78 (GRP78) and osteogenic specific transcription factor Runt related transcription factor 2(RUNX2) decreased significantly (P<0.05). However, miR-30d-5p inhibitor-treated the cells with increased osteogenic differentiation and mineralization ability (P < 0.05), and apoptosis level decreased (P < 0.05). GRP78 and RUNX2 protein levels increased (P<0.05). The miR-30d-5p binding site was located at 142-148 bp of the 3'UTR of the GRP78 gene. Conclusion MiR-30d-5p inhibits osteogenic differentiation and promotes apoptosis of bone marrow stromal cells by down-regulating the expression of GRP78 protein.

Research progress in noncoding RNAs and cardiac fibrosis / 中国药理学通报

Myocardial fibrosis is a common pathological feature in various advanced cardiovascular diseases, and progressive fibrosis is the pathological basis for the development and progression of many cardiac arrhythmias and heart failure. There are no effective reversal drugs for myocardial fibrosis, which is related to the lack of understanding of the molecular mechanisms. Noncoding RNAs are a class of RNAs that do not function as coding proteins, and have been found to be intimately involved in the life cycle of cardiomyocyte differentiation, transcription and apoptosis, and are important regulators of cardiovascular diseases. An increasing number of studies have shown that noncoding RNAs regulate the proliferation and transformation of cardiac fibroblasts through related signaling pathways and can be used as potential biomarkers and novel therapeutic targets for cardiac fibrosis. This article reviews the relationship between noncoding RNAs and cardiac fibrosis.

A control study of steroid withdrawal protection strategy after kidney transplantation in children / 中华儿科杂志

Objective: To study the influence of steroid withdrawal protection strategy on height growth in pediatric patients after kidney transplantation. Methods: The prospective cohort study enrolled 40 stage 5 chronic kidney disease children receiving kidney transplantation from July 2017 to September 2022 at Guangzhou Women and Children's Medical Center. Based on the primary preoperative disease, patients with immune abnormality-associated glomerular diseases or unknown causes were assigned to the steroid maintenance group, in which patients received steroid tapering within 3 months after surgery to a maintenance dose of 2.5 to 5.0 mg/d. While patients with hereditary kidney disease or congenital urinary malformations were assigned to the steroid withdrawal group, in which patients had steroids tapered off within 3 months. The characteristics of height catch-up growth and clinical data were compared between the 2 groups at baseline, 6, 12, 18 and 24 months after kidney transplantation. T-test, repeated measurement of variance analysis, Mann-Whitney U test, and Fisher exact test were used for the comparison between the 2 groups. Results: Among the 40 children, 17 were males, 23 were females, 25 were in the steroid withdraw group ((7.8±2.8) years old when receiving kidney transplantation) and 15 cases were in the steroid maintenance group ((7.6±3.5) years old when receiving kidney transplantation). The study population was followed up for (26±12) months. The total dose per unit body weight of steroids in the steroid withdrawal group was lower than that in the steroid maintenance group ((0.13±0.06) vs. (0.36±0.19) mg/(kg·d), t=5.83, P<0.001). The height catch-up rate (ΔHtSDS) in the first year after kidney transplantation in the steroid withdraw and steroid maintenance groups was 1.0 (0.7, 1.4) and 0.4 (0.1, 1.0), respectively; in the second year, the ΔHtSDS in the steroid withdraw group was significantly higher than that in the steroid maintenance group (1.1 (0.2, 1.7) vs. 0.3 (0, 0.8), U=28.00, P=0.039). The HtSDS in the steroid withdrawal group at the five follow-up time points was -2.5±0.8, -2.0±0.8, -1.5±0.8, -1.3±0.9 and -0.5±0.3, respectively, while in the steroid maintenance was -2.4±1.3, -2.2±1.1, -2.0±1.0, -1.8±1.0 and -1.6±1.0, respectively. There were statistically significant differences in HtSDS at different follow-up time points in both 2 groups (F=19.81, P<0.01), but no statistical differences in overall impact between the 2 groups (F=1.13, P=0.204). The steroid treatment was interaction with the increase of follow-up time (F=3.62, P=0.009). At the 24th month after transplantation, the HtSDS in the steroid withdrawal group was significantly higher than that in the steroid maintenance group (P=0.047). Six patients in the steroid withdrawal group experienced antibody-mediated immune rejection (AMR), while 3 did in the steroid maintenance group. Moreover, there was no significant difference in AMR between the two groups (χ2=0.06, P=0.814). Conclusion: The steroid withdrawal protection strategy favors the height catch-up growth in pediatric patients after kidney transplantation and does not increase the risk of postoperative antibody-mediated immune rejection.

Report content and prenatal diagnosis of non-invasive prenatal testing for sex chromosome aneuploidy / 中华妇产科杂志

Objective: To analyze the report content, the methods and results of prenatal diagnosis of high risk of sex chromosome aneuploidy (SCA) in non-invasive prenatal testing (NIPT). Methods: A total of 227 single pregnancy pregnant women who received genetic counseling and invasive prenatal diagnosis at Drum Tower Hospital Affiliated to the Medical School of Nanjing University from January 2015 to April 2022 due to the high risk of SCA suggested by NIPT were collected. The methods and results of prenatal diagnosis were retrospectively analyzed, and the results of chromosome karyotype analysis and chromosome microarray analysis (CMA) were compared. The relationship between NIPT screening and invasive prenatal diagnosis was analyzed. Results: (1) Prenatal diagnosis methods for 277 SCA high risk pregnant women included 73 cases of karyotyping, 41 cases of CMA and 163 cases of karyotyping combined with CMA, of which one case conducted amniocentesis secondly for further fluorescence in situ hybridization (FISH) testing. Results of invasive prenatal diagnosis were normal in 166 cases (59.9%, 166/277), and the abnormal results including one case of 45,X (0.4%, 1/277), 18 cases of 47,XXX (6.5%, 18/277), 36 cases of 47,XXY (13.0%, 36/277), 20 cases of 47,XYY (7.2%, 20/277), 1 case of 48,XXXX (0.4%, 1/277), 20 cases of mosaic SCA (7.2%, 20/277), 5 cases of sex chromosome structural abnormality or large segment abnormality (1.8%, 5/277), and 10 cases of other abnormalities [3.6%, 10/277; including 9 cases of copy number variation (CNV) and 1 case of balanced translocation]. Positive predictive value (PPV) for SCA screening by NIPT was 34.7% (96/277). (2) Among the 163 cases tested by karyotyping combined with CMA, 11 cases (6.7%, 11/163) showed inconsistent results by both methods, including 5 cases of mosaic SCA, 1 case of additional balanced translocation detected by karyotyping and 5 cases of additional CNV detected by CMA. (3) NIPT screening reports included 149 cases of "sex chromosome aneuploidy"(53.8%, 149/277), 54 cases of "number of sex chromosome increased" (19.5%, 54/277), and 74 cases of "number of sex chromosome or X chromosome decreased" (26.7%, 74/277). The PPV of "number of sex chromosome increased" and "number of sex chromosome or X chromosome decreased" were 72.2% (39/54) and 18.9% (14/74), respectively, and the difference was statistically significant (χ2=34.56, P<0.01). Conclusions: NIPT could be served as an important prenatal screening technique of SCA, especially for trisomy and mosaicism, but the PPV is comparatively low. More information of NIPT such as the specific SCA or maternal SCA might help improving the confidence of genetic counseling and thus guide clinic management. Multi technology platforms including karyotyping, CMA and FISH could be considered in the diagnosis of high risk of SCA by NIPT.

Longitudinal proteomic investigation of COVID-19 vaccination

Although the development of COVID-19 vaccines has been a remarkable success, the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict. In this study, blood samples were collected from 163 participants who next received two doses of an inactivated COVID-19 vaccine (CoronaVac®) at a 28-day interval. Using TMT-based proteomics, we identified 1,715 serum and 7,342 peripheral blood mononuclear cells (PBMCs) proteins. We proposed two sets of potential biomarkers (seven from serum, five from PBMCs) at baseline using machine learning, and predicted the individual seropositivity 57 days after vaccination (AUC = 0.87). Based on the four PBMC's potential biomarkers, we predicted the antibody persistence until 180 days after vaccination (AUC = 0.79). Our data highlighted characteristic hematological host responses, including altered lymphocyte migration regulation, neutrophil degranulation, and humoral immune response. This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after COVID-19 vaccination, shedding light on immunization mechanisms and individual booster shot planning.

Meta-analysis of therapeutic effect of intense pulsed light combined with meibomian gland expression on meibomian gland dysfunction related dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To systematically evaluate the efficacy of intense pulsed light(IPL)combined with meibomian gland expression(MGX)in the treatment of meibomian gland dysfunction(MGD)-related dry eye disease(DED).METHODS: Chinese and English databases such as Chinese national knowledge infrastructure(CNKI), Wanfang, VIP, CBM, ClinicalTrials, PubMed, Embase and Web of Science were searched, and clinical randomized controlled trials(RCTs)using IPL combined with MGX in the experimental group and MGX alone in the control group from January 2017 to September 2022 were included. Six outcome indicators including clinical efficacy, ocular surface disease index(OSDI)score, break-up time(BUT), corneal fluorescein staining(CFS)score, tear meniscus height(TMH)and meibomian gland yielding secretion score(MGYSS)were Meta analyzed by Review Manager 5.3 and Stata 14 software.RESULTS: A total of 15 RCTs were included, with 1 345 patients with MGD-related dry eye. Meta-analysis results showed that the treatment of MGD-related dry eye in the experimental group improved better clinical efficacy(OR=4.95, 95%CI: 2.76～8.90, Z=5.35, P&#x0026;#x003C;0.00001), BUT(SMD=1.26, 95%CI: 0.84～1.69, Z=5.78, P&#x0026;#x003C;0.00001), TMH(SMD=0.37, 95%CI: 0.15～0.59, Z=3.33, P=0.0009), and reduced OSDI scores(SMD=-0.86, 95%CI: -1.44～-0.27, Z=2.85, P=0.004)as well as MGYSS(SMD=-2.43, 95%CI: -4.31～-0.54, Z=2.52, P=0.01)than the control group. However, there was no statistically significant difference in CFS scores(SMD=-0.19, 95%CI: -0.46～0.07, Z=1.43, P=0.15).CONCLUSION: IPL combined with MGX in the treatment of MGD related dry eye can increase the overall effective rate and improve the symptoms and signs of patients with MGD related dry eye better than MGX alone.

Diagnostic Value of American Thyroid Association Guidelines,American College of Radiology Thyroid Imaging Reporting and Data System,and Chinese Thyroid Imaging Reporting and Data System Alone and Combined With BRAFV600E Mutation in Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance / 中国医学科学院学报

Objective To explore the diagnostic efficacy of American Thyroid Association(ATA)guidelines,American College of Radiology Thyroid Imaging Report and Data System(ACR-TIRADS),and Chinese Thyroid Imaging Reporting and Data System(C-TIRADS)alone and combined with BRAFV600E mutation in atypia of undetermined significance/follicular lesion of undetermined significance(AUS/FLUS).Methods A total of 138 patients who underwent ultrasound-guided fine needle aspiration(FNA)in the Chinese PLA General Hospital from January 2020 to May 2023 were selected.The clinicopathological and ultrasound characteristics were retrospectively analyzed for each nodule.Each nodule underwent preoperative BRAFV600E mutation testing and was diagnosed according to the ATA guidelines,ACR-TIRADS,and C-TIRADS.The diagnostic efficacy of ATA guidelines,ACR-TIRADS,and C-TIRADS alone and combined with BRAFV600E mutation was assessed based on the results of histopathological diagnosis.Results The 138 AUS/FLUS thyroid nodules included 45(32.6%)benign ones and 93(67.4%)malignant ones.The patient age(t=1.444,P=0.151),gender(χ2=0.259,P=0.611),and location of nodules(χ2=2.055,P=0.358)had no statistical significance for the differentiation between benign and malignant nodules,while nodule size(Z=2.500,P=0.012),echo(χ2=14.693,P<0.001),composition(χ2=17.075,P<0.001),aspect ratio ≥1(χ2=9.477,P=0.002),and microcalcification(χ2=6.892,P=0.009)were of significance for the differentiation.When applied alone,BRAFV600E mutation showed high specificity(95.56%)and positive predictive value(95.65%).Among the three ultrasound grading systems,ACR-TIRADS had the highest sensitivity(χ2=37.923,P<0.001;χ2=40.462,P<0.001)and accuracy(χ2=81.595,P<0.001;χ2=76.912,P<0.001),while C-TIRADS had the highest specificity(χ2=11.746,P<0.001;χ2=21.235,P<0.001).However,the three systems showed no statistically significant difference in the diagnostic efficiency when applied alone(Z=1.177,P=0.239;Z=0.213,P=0.831;Z=1.016,P=0.310).The combination of BRAFV600E mutation with ACR-TIRADS or C-TIRADS improved the diagnostic efficacy of BRAFV600E mutation in distinguishing the benign and malignant AUS/FLUS nodules(Z=2.107,P=0.035;Z=2.752,P=0.006).The combination of ATA guidelines with BRAFV600E mutation increased the diagnostic accuracy of BRAFV600E mutation(χ2=20.679,P<0.001),while it had no statistically significant difference in distinguishing the benign and malignant AUS/FLUS nodules(Z=1.321,P=0.186).The combination of ATA guidelines,ACR-TIRADS,or C-TIRADS with BRAFV600E mutation improved the diagnostic efficacy of ultrasound grading systems for AUS/FLUS nodules(Z=2.770,P=0.006;Z=2.770,P=0.006;Z=2.890,P=0.004).Specifically,ACR-TIRADS combined with BRAFV600E mutation showed the highest sensitivity(χ2=4.712,P=0.030;χ2=4.712,P=0.030),while C-TIRADS combined with BRAFV600E mutation showed the highest accuracy(χ2=77.627,P<0.001;χ2=85.827,P<0.001).However,there were no statistically significant differences in diagnostic performance between the combinations(Z=1.276,P=0.202;Z=0.808,P=0.419;Z=1.615,P=0.106).Conclusion ATA guidelines,ACR-TIRADS,and C-TIRADS combined with BRAFV600E mutation can improve the diagnostic efficacy of BRAFV600E mutation or ultrasound grading system alone in AUS/FLUS nodules,which can facilitate the further management and treatment of such patients.

Adaptation of the electron transport chain improves the biocatalytic efficiency of progesterone 17α hydroxylation / 生物工程学报

17α hydroxylase is a key enzyme for the conversion of progesterone to prepare various progestational drug intermediates. To improve the specific hydroxylation capability of this enzyme in steroid biocatalysis, the CYP260A1 derived from cellulose-mucilaginous bacteria Sorangium cellulosum Soce56 and the Fpr and bovine adrenal-derived Adx4-108 derived from Escherichia coli str. K-12 were used to construct a new electron transfer system for the conversion of progesterone. Selective mutation of CYP260A1 resulted in a mutant S276I with significantly enhanced 17α hydroxylase activity, and the yield of 17α-OH progesterone reached 58% after optimization of the catalytic system in vitro. In addition, the effect of phosphorylation of the ferredoxin Adx4-108 on 17α hydroxyl activity was evaluated using a targeted mutation technique, and the results showed that the mutation Adx4-108T69E transferred electrons to S276I more efficiently, which further enhanced the catalytic specificity in the C17 position of progesterone, and the yield of 17α-OH progesterone was eventually increased to 74%. This study provides a new option for the production of 17α-OH progesterone by specific transformation of bacterial-derived 17α hydroxylase, and lays a theoretical foundation for the industrial production of progesterone analogs using biotransformation method.

DJ1 Ameliorates AD-like Pathology in the Hippocampus of APP/PS1 Mice / 生物医学与环境科学（英文）

OBJECTIVE@#To explore whether the protein Deglycase protein 1 (DJ1) can ameliorate Alzheimer's disease (AD)-like pathology in Amyloid Precursor Protein/Presenilin 1 (APP/PS1) double transgenic mice and its possible mechanism to provide a theoretical basis for exploring the pathogenesis of AD.@*METHODS@#Adeno-associated viral vectors (AAV) of DJ1-overexpression or DJ1-knockdown were injected into the hippocampus of 7-month-old APP/PS1 mice to construct models of overexpression or knockdown. Mice were divided into the AD model control group (MC), AAV vector control group (NC), DJ1-overexpression group (DJ1 +), and DJ1-knockdown group (DJ1 -). After 21 days, the Morris water maze test, immunohistochemistry, immunofluorescence, and western blotting were used to evaluate the effects of DJ1 on mice.@*RESULTS@#DJ1 + overexpression decreased the latency and increased the number of platform traversals in the water maze test. DJ1 - cells were cured and atrophied, and the intercellular structure was relaxed; the number of age spots and the expression of AD-related proteins were significantly increased. DJ1 + increased the protein expression of Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), light chain 3 (LC3), phosphorylated AMPK (p-AMPK), and B cell lymphoma-2 (BCL-2), as well as the antioxidant levels of total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), and Glutathione peroxidase (GSH-PX), while decreasing the levels of Kelch-like hydrates-associated protein 1 (Keap1), mammalian target of rapamycin (mTOR), p62/sequestosome1 (p62/SQSTM1), Caspase3, and malondialdehyde (MDA).@*CONCLUSION@#DJ1-overexpression can ameliorate learning, memory, and AD-like pathology in APP/PS1 mice, which may be related to the activation of the NRF2/HO-1 and AMPK/mTOR pathways by DJ1.

Isolation of Leclercia adecarboxylata Producing Carbapenemases in A Newborn Female / 生物医学与环境科学（英文）

Leclercia adecarboxylata is a Gram-negative bacterium belonging to the Enterobacteriaceae family. To our knowledge, this is the first report of a carbapenem-resistant L. adecarboxylata strain isolated from a healthy newborn. The L. adecarboxylata strain isolated in this study carried four plasmids that may serve as reservoirs for antibiotic resistance genes. Plasmids 2 and 4 did not harbor any antimicrobial resistance genes. Plasmid 3 is a novel plasmid containing three resistance genes. The bla IMP gene harbored in the strain was most similar to bla IMP-79 at the nucleotide level, with a similarity of 99.4% (737/741). This case highlights the importance of considering L. adecarboxylata as a potential cause of infections in children.