National tertiary public hospital performance appraisal: Using FOCUS-PDCA to improve external quality assessment.

PURPOSE: To innovatively use the FOCUS-PDCA quality improvement strategy to establish an external quality assessment (EQA) working group to continuously improve EQA performance, an important indicator of the national tertiary public hospital performance appraisal. METHODS: The project was carried out at the National Center for Clinical Laboratories. Using FOCUS-PDCA, which combines problem-focused steps (FOCUS) and improvement steps (PDCA), a project team was established to carry out improvement work. Root cause analysis was carried out to analyze the problems in quality control from EQA project application to results analysis and an improvement plan was implemented according to the steps of FOCUS-PDCA. The project was executed in three cycles from 2019 to 2021 to obtain more satisfactory results. RESULTS: After implementing three cycles of FOCUS-PDCA, the EQA participation rate increased from 66.5% in 2018 to 100% in 2021, and the EQA pass rate increased from 94.9% in 2018 to 99.3% in 2021. Consequently, the hospital moved into the top 50 in performance assessment for the first time in 2020 and ranked 27th in 2021. CONCLUSION: The use of the FOCUS-PDCA quality improvement strategy can improve the EQA performance of national tertiary public hospitals and help them achieve satisfactory results in the national examination.

Identifying SLC2A6 as the novel protective factor in breast cancer by TP53-related genes affecting M1 macrophage infiltration.

The high heterogeneity of breast cancer (BC) caused by pathogenic gene mutations poses a challenge to immunotherapy, but the underlying mechanism remains unknown. The difference in the infiltration of M1 macrophages induced by TP53 mutations has a significant impact on BC immunotherapy. The aim of this study was to develop a TP53-related M1 macrophage infiltration molecular typing risk signature in BC and evaluate the biological functions of the key gene to find new immunotherapy biomarkers. Weighted correlation network analysis (WGCNA) and negative matrix factorization (NMF) were used for distinguishing BC subtypes. The signature and the nomogram were both constructed and evaluated. Biological functions of the novel signature gene SLC2A6 were confirmed through in vitro and in vivo experiments. RNA-Sequencing and protein profiling were used for detecting the possible mechanism of SLC2A6. The results suggested that four BC subtypes were distinguished by TP53-related genes that affect M1 macrophage infiltration. The signature constructed by molecular typing characteristics could evaluate BC's clinical features and tumor microenvironment. The nomogram could accurately predict the prognosis. The signature gene SLC2A6 was found to have an abnormally low expression in tumor tissues. Overexpression of SLC2A6 could inhibit proliferation, promote mitochondrial damage, and result in apoptosis of tumor cells. The HSP70 family member protein HSPA6 could bind with SLC2A6 and increase with the increased expression of SLC2A6. In summary, the risk signature provides a reference for BC risk assessment, and the signature gene SLC2A6 could act as a tumor suppressor in BC.

A Novel Pair of Compound Heterozygous Mutation of EYS in a Han Chinese Family with Retinitis Pigmentosa.

Background: Retinitis pigmentosa (RP) is a complex inherited and progressive degenerative retinal disease. The eyes shut homolog (EYS) is frequently associated with RP is surprisingly high. Exploring the function of EYS is quite difficult due to the unique gene size and species specificity. Gene therapy may provide a breakthrough to treat this disease. Therefore, exploring and clarifying pathogenic mutations of EYS-associated RP has important guiding significance for clinical treatment. Methods: Clinical and molecular genetic data for EYS-associated RP were retrospectively analyzed. Sanger sequencing was applied to identify novel mutations in these patients. Candidate pathogenic variants were subsequently evaluated using bioinformatic tools. Results: A novel pair of compound heterozygous mutations was identified: a novel stop-gain mutation c.2439C>A (p.C813fsX) and a frameshift deletion mutation c.6714delT (p. P2238fsX) of the EYS gene in the RP family. Both of these mutations were rare or absent in the 1000 Genomes Project, dbSNP, and Genome Aggregation Database (gnomAD). These two mutations would result in a lack of multiple functionally important epidermal growth factor-like and Laminin G-like coding regions in EYS. Conclusions: A novel compound heterozygote of the EYS gene in a Chinese family with an autosomal inheritance pattern of RP was identified. Identifying more pathogenic mutations and expanding the mutation spectrum of the EYS gene will contribute to a more comprehensive understanding of the molecular pathogenesis of RP disease that could be gained in the future. It also could provide an important basis for the diagnosis, clinical management, and genetic counseling of the disease.

Identification of mutation gene prognostic biomarker in multiple myeloma through gene panel exome sequencing and transcriptome analysis in Chinese population.

BACKGROUND: The 5-year survival rate of multiple myeloma (MM) in China is less than 40%, with considerable individual heterogeneity. Gene mutations are important predictive biomarkers that influence MM treatment decision. The aim of our study was to uncover the clinical significance of mutated genes in MM in the Chinese population. METHODS: Targeted exon panel sequencing was performed of 400 genes to detect the gene mutation status in plasma cells from 50 patients with MM. DAVID was used to explore the functions and pathways of mutated genes. Detection of mutant gene expression, prognosis and immune cell infiltration with GSE6477. GEO2R was utilized to identify differentially expressed genes (DEGs). Kaplan-Meier and CIBERSORT were applied to compare survival distributions and evaluate the gene expression associated with immune cell infiltration, respectively. RESULTS: Mutations of 337 genes were identified in MM. The mutation types included SNP, INS, and DEL, but the dominant mutation type was SNP. Function and pathway analysis of mutant genes were performed to elucidate DNA modifications. We identified a total number of 660 downregulated and 587 upregulated genes from the GSE6477 dataset. Thirty-three common genes were present in both the mutant genes and DEGs. The functions and pathways of the mutated genes were enriched in myeloid cell differentiation, regulation of hemopoiesis, etc. Moreover, we found that the low expression of BCL6, BIRC3, HLA-DQA1, and VCAN was correlated with poor prognosis in MM. CONCLUSIONS: The mutations and low expression of BCL6, BIRC3, HLA-DQA1, and VCAN were correlated with poor prognosis and immune cell infiltration in MM. This study is the first to reveal the spectrum of mutations in the Chinese population by the use of an NGS panel.

Nanotechnology Lighting the Way for Gene Therapy in Ophthalmopathy: From Opportunities toward Applications.

Hereditary ophthalmopathy is a well-described threat to human visual health affecting millions of people. Gene therapy for ophthalmopathy has received widespread attention with the increasing understanding of pathogenic genes. Effective and safe delivery of accurate nucleic acid drugs (NADs) is the core of gene therapy. Efficient nanodelivery and nanomodification technologies, appropriate targeted genes, and the choice of drug injection methods are the guiding lights of gene therapy. Compared with traditional drugs, NADs can specifically change the expression of specific genes or restore the normal function of mutant genes. Nanodelivery carriers can improve targeting and nanomodification can improve the stability of NADs. Therefore, NADs, which can fundamentally solve pathogeny, hold great promise in the treatment of ophthalmopathy. This paper reviews the limitations of ocular disease treatment, discusses the classification of NADs in ophthalmology, reveals the delivery strategies of NADs to improve bioavailability, targeting, and stability, and summarizes the mechanisms of NADs in ophthalmopathy.

ANALYSIS OF THE REFRESHER PERSONNEL STRUCTURE IN THE CLINICAL LABORATORY OF A 3A HOSPITAL CHINA.

To analyze the changes in refresher personnel structure in a clinical laboratory of a 3A hospital, understand the development trends in laboratory science, and provide a reference for refresher training in various hospitals. The basic information of the trainees in the institute from January 2009 to December 2018 was collected and analyzed with respect to gender, age, educational background, professional title, duration of training, number of trainees in sub-majors, and number of months of training in sub-majors. In the past 10 years, the gender of the trainees in the institute was mostly female. The educational level and professional title of the trainees have gradually increased. The training period was most often 6 months, and the sub-majors were mostly clinical microbiology and bone marrow cytology. With the change in the social environment, the structure and needs of personnel refresher training will change. Each hospital should reasonably plan the enrollment scale and scientifically formulate training plans and programs to meet the needs of continuing education in the new era.

BRCA2 gene mutation in cancer.

Breast cancer susceptibility gene 2 (BRCA2) is the main gene associated with hereditary breast cancers. However, a mutation in BRCA2 has also been found in other tumors, such as ovarian, pancreatic, thyroid, gastric, laryngeal, and prostate cancers. In this review, we discuss the biological functions of BRCA2 and the role of BRCA2 mutations in tumor progression and therapy.

Revised International Staging System (R-ISS) stage-dependent analysis uncovers oncogenes and potential immunotherapeutic targets in multiple myeloma (MM).

Multiple myeloma (MM) accounts for ~10% of all haematologic malignancies. Little is known about high intratumour heterogeneities in patients stratified by the Revised International Staging System (R-ISS). Herein, we constructed a single-cell transcriptome atlas to compare differential expression patterns among stages. We found that a novel cytotoxic plasma cell (PC) population exhibited with NKG7 positive was obviously enriched in stage II patients. Additionally, a malignant PC population with significantly elevated expression of MKI67 and PCNA was associated with unfavourable prognosis and Epstein-Barr virus (EBV) infection in our collected samples. Moreover, ribonucleotide reductase regulatory subunit M2 (RRM2) was found and verified to promote proliferation of MM cell lines, suggesting RRM2 may serve as a detrimental marker in MM. The percentages of CD8+ T cells and NKT cells decreased along with R-ISS stages, reflecting the plasticity of the tumour immune microenvironment. Importantly, their crosstalks with myeloid cells and PC identified several potential immunotargets such as SIRPA-CD47 and CD74-MIF, respectively. Collectively, this study provided an R-ISS-related single-cell MM atlas and revealed the clinical significance of novel PC clusters, as well as potential immunotargets in MM progression.

Multiple myeloma is a type of bone cancer. It affects the immune cells that make antibodies, known as plasma cells. These immune cells live in the bone marrow. As with many types of cancer, the chance of survival is highest when multiple myeloma is diagnosed early. It has three stages, labelled I, II, and III. People with stage I or II disease have better outcomes than those with stage III, but the exact reasons are unclear. Bone marrow contains lots of different types of cells, which can affect the growth of a tumour. These include cancer-targeting cells, called killer T-cells, and cancer-supporting cells called myeloid cells. Understanding these cells and how they interact could shed light on the different stages of multiple myeloma. One way to do this is to use single cell sequencing, which looks at the genes in use inside each cell at any one time. Zhong, Hao, Zhang, Jiang et al. examined the bone marrow of two healthy donors and nine people with different stages of multiple myeloma. This revealed two new groups of plasma cells. One group, highest in stage II patients, was protective, with the potential to kill cancer cells. The other, highest in people with more aggressive disease, was harmful, with the potential to divide rapidly. The sequencing also identified molecules that might be useful drug targets for the future. These included a gene that drove growth in the dangerous plasma cells, and several that might help tumours escape from the immune system. It is becoming increasingly clear that the environment around a tumour has a huge role to play in its progression. Understanding how this environment changes over time could aid in the development of more targeted treatments. The next step is to find out more about the molecules identified here.

FOCUS-PDCA can effectively optimize the critical value of test items: FOCUS-PDCA moze efikasno da optimizuje kriticnu vrednost ispitivanja.

Background: To optimize the critical value of test items using FOCUS-PDCA (find, organize, clarify, understand, select, plan, do, check and act), and to set the personalized critical value of the test for different departments. Methods: We searched for literature reporting on the critical value and FOCUS-PDCA published over recent 5 years in order to understand the significance and status quo of critical value and FOCUS-PDCA. We also collected and analyzed the critical value data of hospital tests performed in Sichuan province hospitals in 2019, which were later compared to data from 2020 to determine the FOCUSPDCA cycle. Results: The proportion of critical values in the whole hospital decreased from 3.5% before optimization to 2.5% to 3% after optimization. The critical values of ICU, hematology, nephrology, urology, and neonatal departments after optimization significantly decreased compared with those before optimization, while the critical values of cardiac surgery, emergency ICU, cardiology, and neurosurgery ICU showed no significant difference before and after optimization. Contrary, the critical values of the infection department after optimization significantly increased before optimization. Conclusions: FOCUS-PDCA can effectively optimize the critical value of test items, which is beneficial for rational utilization of medical resources.

Genetic landscape of FOXC2 mutations in lymphedema-distichiasis syndrome: Different mechanism of pathogenicity for mutations in different domains.

Lymphedema-dissociated syndrome (LDS), of which the pathogenesis is not fully understood, afflicts many patients. In this study, we investigated the effect of FOXC2 gene loss-of-function on the development of LDS disease. Two Han Chinese families with LDS were recruited in this study, pathogenic mutations were identified by Sanger sequencing. Reverse-transcription PCR, subcellular localization, dual fluorescein enzymes, and other in vitro experiments were used to study the functional effects of eight FOXC2 mutations. Two pathogenic FOXC2 duplication mutations (c.930_936dup and c.931-937dup) were identified in the two families. Both mutations caused uneven distribution in the nucleus and a chromatin contraction phenotype, weakening the DNA binding activity and transcription activity. We then performed functional analysis on six additional mutations in different domains of FOXC2 that were reported to cause LDS. We found mutations located in the forkhead domain and central region dramatically reduced the transactivation ability, while mutations in activation domain-2 enhanced this ability. All 8 mutations down-regulated the transcription of ANGPT2 and affected the activity of the ERK-RAS pathway, which may cause abnormal formation of lymphatic vessels. Our findings also showed that all 8 mutations decreased the ability of interaction between FOXC2 and the Wnt4 promoter, suggesting mutations in FOXC2 may also affect the Wnt4-Frizzled-RYK signaling pathway, leading the abnormal differentiation of the meibomian glands into hair follicle cells during the embryonic period and causing distichiasis. This study expanded and revealed the potential pathogenesis mechanism.

Association of genetic variants in PDGFRA with high myopia in the Han population of southwestern China.

PURPOSE: To investigate the associations of 11 genetic single nucleotide polymorphisms (SNPs) in FRAP1 and PDGFRA with high myopia (HM) in a Han Chinese population. METHODS: A total of 442 HM patients and 947 healthy controls were recruited for this study. Five genetic models were analysed to further evaluate the association of target SNPs with HM. SNP functional annotation database tools were used to predict and analyse the potential function of these SNPs. RESULTS: Our findings indicated that rs2114039 located in PDGFRA had significant association with HM in a Han Chinese population (P = 2.00E-06, OR = 0.647, 95%CI = 0.542-0.773). The common genotypes rs2114039CC, rs2114039CT and rs2114039CT+TT all had a decreased risk of HM when compared with rs2114039TT (P = 4.10E-05, OR = 0.290, 95%CI = 0.161-0.524; P = 1.00E-03, OR = 0.626, 95%CI = 0.479-0.819; P = 9.00E-06, OR = 0.560, 95%CI = 0.433-0.724, respectively). In addition, compared with rs2114039CT+TT, rs2114039CC also had a decreased risk of HM (P = 3.59E-04, OR = 0.347, 95% CI = 0.194-0.620). CONCLUSIONS: Our findings indicated that rs2114039, located in PDGFRA, was significantly associated with HM in the southwest Han Chinese population. Additionally, rs2114039 might influence the function of PDGFRA by regulating the growth of human vision through different pathways. Furthermore, functional research on the role of PDGFRA in myopia pathogenesis should be conducted in the future.

Ethnic, geographic, and seasonal differences of vitamin D status among adults in south-west China.

BACKGROUND: There are limited data on vitamin D status of Sichuan province, and no investigation has been carried out on the correlations of 25(OH)D and BTMs between healthy Hans and Tibetans of Sichuan province. This study aimed to examine 25(OH)D levels around Sichuan province and to assess differences by ethnicity, age, gender, sunlight exposure, geographic location, and seasons. METHODS: Blood samples from 2317 healthy adults aged of 18 to 75 years and of Han and Tibetan ethnicities were collected in six regions and during four seasons. Serum 25(OH)D2 and 25(OH)D3 levels were measured by LC-MS/MS method. Serum total P1NP and ß-CTX were measured by immunoassay. RESULTS: Participants aged 18-40 years showed significantly lower 25(OH)D levels than participants aged 41-75 years old (P < .0001). The median serum 25(OH)D level for males was significantly higher than that of females (P < .0001). Serum 25(OH)D levels among four seasons and different districts varied significantly (P < .0001). In addition, the 25(OH)D level of Tibetans was significantly lower than that of Hans, while the serum total P1NP and ß-CTX levels of Tibetans were significantly higher than those of Hans (P < .0001). CONCLUSION: Adult population was more common to have vitamin D deficiency/insufficiency among Tibetans, females, north regions and in spring and winter.

Author Correction: Seroprevalence of immunoglobulin M and G antibodies against SARS-CoV-2 in China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Seroprevalence of immunoglobulin M and G antibodies against SARS-CoV-2 in China.

Detection of asymptomatic or subclinical novel human coronavirus SARS-CoV-2 infection is critical for understanding the overall prevalence and infection potential of COVID-19. To estimate the cumulative prevalence of SARS-CoV-2 infection in China, we evaluated the host serologic response, measured by the levels of immunoglobulins M and G in 17,368 individuals, in the city of Wuhan, the epicenter of the COVID-19 pandemic in China, and geographic regions in the country, during the period from 9 March 2020 to 10 April 2020. In our cohorts, the seropositivity in Wuhan varied between 3.2% and 3.8% in different subcohorts. Seroposivity progressively decreased in other cities as the distance to the epicenter increased. Patients who visited a hospital for maintenance hemodialysis and healthcare workers also had a higher seroprevalence of 3.3% (51 of 1,542, 2.5-4.3%, 95% confidence interval (CI)) and 1.8% (81 of 4,384, 1.5-2.3%, 95% CI), respectively. More studies are needed to determine whether these results are generalizable to other populations and geographic locations, as well as to determine at what rate seroprevalence is increasing with the progress of the COVID-19 pandemic. Serologic surveillance has the potential to provide a more faithful cumulative viral attack rate for the first season of this novel SARS-CoV-2 infection.

Prevalence and Genotype Distribution of Human Papillomavirus From 9,182 Individuals Participated Health Examination.

BACKGROUND: Human papillomavirus (HPV) is the cause of nearly all cervical cancers and the primary cause of anal cancers. Prevalence of HPV varies largely among countries and regions, and population-based data are largely insufficient. The aim of this study is to determine the prevalence and genotype distribution of HPV infection among the women received a general health check. METHODS: In the years 2015, 2016, and 2017, a total of 553,654 individuals received a general health check in the Sichuan Provincial People's Hospital. Among them, 9,182 unselected and asymptomatic individuals received the HPV screening test. Samples of exfoliated endocervical cells were collected and DNA isolation was performed with a Cell Lysis Kit. Fragments of HPV DNA were amplified by PCR. Twenty-one different HPV genotypes, including HPV 6, 11, 16, 18, 31, 33, 35, 39, 42, 43, 44, 45, 51, 52, 53, 56, 58, 59, 66, 68, and CP8304, were detected from PCR products using a GenoArray Diagnostic Hybridization Kit. HPV genotype was read on the colored position on the array. RESULTS: A total of 1,207 individuals were positive for at least one HPV genotype, giving a crude prevalence of 13.2% (95% CI: 12.5 - 13.9%). The prevalence did not differ much among age groups. HPV-positive individuals were 291, 389, and 527 in 2015, 2016, and 2017, respectively. The majority of the HPV-positive participants (960/1,207 = 80%) had one type of virus. Approximately 15% had two genotypes of HPV. One individual had HPV of 6 different genotypes, including 16, 18, 52, 53, 56, and CP8304. The most frequent genotype was 52, followed by CP8304, 58, and 53. The oncogenic types 16 and 18 were found in 112 and 52 participants, corresponding to a prevalence of 0.9% (CI: 0.8 - 1.1%) and 0.4% (CI: 0.3 - 0.6%), respectively, for the 9,182 individuals included in this study. CONCLUSIONS: The prevalence of 13.2% for HPV among unselected and asymptomatic individuals who received a general health check is high in the Sichuan area. Identification of high-risk HPV types is essential for preventing or early detection of cervical cancers and consequently save life.

Comparison of different samples for 2019 novel coronavirus detection by nucleic acid amplification tests.

An ongoing outbreak of severe respiratory pneumonia associated with the 2019 novel coronavirus has recently emerged in China. Here we report the epidemiological, clinical, laboratory and radiological characteristics of 19 suspect cases. We compared the positive ratio of 2019-nCoV nucleic acid amplification test results from different samples including oropharyngeal swab, blood, urine and stool with 3 different fluorescent RT-PCR kits. Nine out of the 19 patients had 2019-nCoV infection detected using oropharyngeal swab samples, and the virus nucleic acid was also detected in eight of these nine patients using stool samples. None of positive results was identified in the blood and urine samples. These three different kits got the same result for each sample and the positive ratio of nucleic acid detection for 2019-nCoV was only 47.4% in the suspect patients. Therefore, it is possible that infected patients have been missed by using nucleic acid detection only. It might be better to make a diagnosis combining the computed tomography scans and nucleic acid detection.

Frequency of Polycythemia and Other Abnormalities in a Tibetan Herdsmen Population Residing in the Kham Area of Sichuan Province, China.

INTRODUCTION: The Kham Tibetans are one of several Tibetan ethnic subgroups living in the Kham area of China. Because studies on the high-altitude adaptation of the Kham people are scant, the main aim of this study is to investigate whether the response to hypoxia, especially polycythemia status, in the Kham Tibetans is different from other Tibetan ethnic subgroups. METHODS: The primary investigation was conducted on 346 native Kham Tibetan adults (268 men and 78 women) from 3 herdsmen villages located in Hongyuan County situated at an altitude of greater than 3600 m. The participants were aged 46.2±14.1 (21-82; mean±SD with range) years. Anthropometric measurements such as weight, height, waist circumference, body mass index, and blood pressure, as well as laboratory blood tests such as glycosylated hemoglobin, hemoglobin, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and uric acid were analyzed. RESULTS: The concentrations of hemoglobin were 171.3±12.9 (66-229) mg·L-1 and 151.4±16.4 (86-190) mg·L-1 in men and women, respectively. The frequency of polycythemia was found to be 25.5 and 21.8% in men and women, respectively. Polycythemia was found to be significantly associated with glycosylated hemoglobin concentrations, hypertension, and hyperuricemia (P=0.002, 0.023, and 0.009, respectively). CONCLUSIONS: There is a higher frequency of polycythemia in the Kham Tibetans when compared with reported studies from other Tibetan ethnic subgroups living on the Qinghai-Tibet plateau.

Treatment for malignant struma ovarii in the eyes of thyroid surgeons: a case report and study of Chinese cases reported in the literature.

Malignant struma ovarii (MSO) is a rare malignant ovarian germ cell tumor that has been scarcely reported by thyroid surgeons focusing on treatment. There are no golden standards for its treatment. There has not been any Chinese case included in the English language literatures. This is the first study by collecting all Chinese cases with clinical information. We emphasize on using I therapy after operation.Presented is a case of struma ovarii with malignant histologic features who underwent definitive initial surgery of reproductive system tumors and a total thyroidectomy combined with thyroid-stimulating hormone (TSH)-suppressive therapy following treatment with I. Furthermore, a Chinese full-text database literature search for cases of MSO was performed, and advisable clinical data were collected following our treatment advice.Clinical data from 34 additional cases were compiled. As Chinese genetic background and environment are different from those of Western countries, our clinical data closely mirror theirs in some aspects. In addition, we provide a rare gene mutation type of MSO by the case from our department.Integrating literatures with the experience of thyroid surgeons, we recommend "multidisciplinary joint treatment" for MSO, namely traditional radical initial surgery of ovarian cancer and a total thyroidectomy combined with TSH-suppressive therapy following treatment with I for those who do not desire preservation of fertility.

Direct common gram-negative bacterial identification from positive blood culture bottles by SELDI-TOF MS.

A protein database was constructed and validated with identification rate over 90% for the 4 most common Gram-negative bacteria on agar plates. By protein masses comparison, 120 bacteria of the 4 species from blood culture bottles were identified. The concordance was high (Kappa=0.906) between our method and conventional approach.