Single-Slice Hounsfield Unit (HU) Value of the Chinese Proximal Humerus on Routine Chest CT: A Study on Opportunistically Screening for Low Bone Density / Valor de Unidad Hounsfield (HU) de Corte Único del Húmero Proximal Chino en una Tomografía Computarizada de Tórax de Rutina: Un Estudio sobre la Detección Oportunista de Baja Densidad Ósea

SUMMARY: A Study on Relationship between Single-Slice Hounsfield Unit(HU) value of the Chinese proximal humerus and Bone Mineral Density(BMD) Using Routine Chest CT and Dual-energy X-ray Absorptiometry(DEXA) was performed. Data were collected from 240 individuals who underwent DEXA and routine chest CT scans (including full images of the proximal humerus) on the same day at 967 Hospitals between January 2019 and December 2021. The method of measuring single-slice HU values of the proximal humerus on routine chest CT scans exhibited high reliability and repeatability (intraclass correlation coefficient > 0.961, P < 0.001). A strong positive correlation was observed between single-slice HU values of the proximal humerus and DEXA results, with the 20-mm HU value demonstrating the highest correlation. Across different BMI groups, the Area Under Curve (AUC) for the 20-mm HU value was consistently the largest (AUC=0.701- 0.813, P< 0.05). Therefore, the 20-mm HU value can be considered a reliable reference for the opportunistic screening of low BMD, with reference values of -4HU for underweight individuals, -13HU for normal weight individuals, -7HU for overweight individuals, and -16HU for obese individuals. Values below these thresholds indicate a risk of low BMD. This study enriches the Chinese BMD data and offers a swift and effective approach for opportunistically screening low BMD.

Se realizó un estudio sobre la relación entre el valor de la Unidad Hounsfield (HU) de corte único del húmero proximal chino y la densidad mineral ósea (DMO) mediante TC de tórax de rutina y absorciometría de rayos X de energía dual (DEXA). Se recopilaron datos de 240 personas que se sometieron a DEXA y tomografías computarizadas de rutina de tórax (incluidas imágenes completas del húmero proximal) el mismo día en 967 hospitales entre enero de 2019 y diciembre de 2021. El método para medir los valores de HU de un solo corte del húmero proximal en las tomografías computarizadas de tórax mostraron alta confiabilidad y repetibilidad (coeficiente de correlación intraclase > 0,961, P < 0,001). Se observó una fuerte correlación positiva entre los valores de HU de un solo corte del húmero proximal y los resultados de DEXA, demostrando el valor de HU de 20 mm la correlación más alta. En diferentes grupos de IMC, el área bajo la curva (AUC) para el valor HU de 20 mm fue consistentemente el más grande (AUC = 0,701-0,813, P <0,05). Por lo tanto, el valor de HU de 20 mm puede considerarse una referencia fiable para el cribado oportunista de DMO baja, con valores de referencia de -4 HU para personas con bajo peso, -13 HU para personas con peso normal, -7 HU para personas con sobrepeso y -16 HU para personas obesas. Los valores por debajo de estos umbrales indican un riesgo de DMO baja. Este estudio es un aporte para los datos chinos sobre la DMO y ofrece un enfoque rápido y eficaz para detectar de forma oportunista la DMO baja.

Analysis of genetic polymorphisms and a novel tri-allelic cloning sequence for the D13S317 locus among an ethnic Han Chinese population / 中华医学遗传学杂志

OBJECTIVE@#To study the genetic polymorphisms of short-tandem repeats (STR) for the D13S317 locus among an ethnic Han Chinese population and verify a novel tri-allelic pattern identified for the locus.@*METHODS@#A total of 378 paternity test cases from Guangdong Forensic Authentication Institute from October 17, 2017 to December 28, 2017 were selected as the study subjects. A GlobalFilerTM Express kit was used for the STR genotyping. Samples suspected for having a novel tri-allelic pattern were verified with a PowerPlex 21 kit. Potential variant of the primer-binding region and flanking sequences underlying the tri-allelic pattern was excluded by molecular cloning and sequencing.@*RESULTS@#Six alleles were detected for the D13S317 locus, with the characteristic distribution frequencies being 8 (29.1%), 9 (13.1%), 10 (15.21%), 11 (24.21%), 12 (13.89%) and 13 (3.44%), respectively. In one of the families, the D13S317 locus of the proband was suspected to harbor a triband allele (8, 9, 10). A re-test has confirmed the result of initial test. Molecular cloning and sequencing analysis of the D13S317 locus in the proband and his daughter has failed to find allelic variants in the primer-binding region and flanking sequence, which has confirmed the novel tri-allelic pattern for the locus.@*CONCLUSION@#A novel type 2 tri-allelic pattern (8, 9, 10) at the D13S317 locus has been identified among the ethnic Han Chinese population. The pattern has not been transmitted to the female offspring, and has been included in the international STRBase database for the first time.

Genetic analysis of a Chinese pedigree with an allele dropout at the HLA-B locus / 中华医学遗传学杂志

OBJECTIVE@#To delineate a deletional mutation of the HLA-B gene in a Chinese pedigree.@*METHODS@#A female patient with acute myeloid leukemia who had visited Liuzhou People's Hospital in April 2022 was selected as the study subject. Routine human leukocyte antigen (HLA) was determined by using PCR-sequence specific oligonucleotide polymorphism (PCR-SSOP) and PCR-sequence-based typing (PCR-SBT) methods. Next generation sequencing (NGS) was used to validate the candidate variant in the HLA-B gene.@*RESULTS@#The PCR-SBT and SSOP results for the HLA-B locus were inconsistent for the patient and her daughter. The SSOP results of the two individuals were HLA-B*35:01, 40:02 and HLA-B*35:01, 40:01, respectively. However, the PCR-SBT results has indicated a mismatch with the nearest HLA-B*35:01 at exon 4. NGS results showed that the HLA-B*35:01 had a 9 bp deletion in the intron 5. The patient's husband was HLA-B*40:01, 58:01, which was normal.@*CONCLUSION@#The variant in intron 5 of the HLA-B gene in this pedigree has mapped to a primer-binding region for the SBT reagent, which has affected the accuracy of PCR-SBT results.

Very-long chain acyl-coA dehydrogenase deficiency: report of a Chinese pedigree and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To explore the correlation between clinical classification and genotype and prognosis among Chinese children with Very-long chain acyl-CoA dehydrogenase deficiency (VLCADD).@*METHODS@#A Chinese pedigree affected with VLCADD admitted at the First People's Hospital of Yunnan Province in February 2019 was selected as the study subject. The characteristics of disease onset, diagnosis and treatment and prognosis were retrospectively analyzed. Relevant literature was also systematically searched and reviewed.@*RESULTS@#The proband, a 1-year-old boy, had the clinical manifestations of frequently vomiting, hypoglycemia, abnormal liver function and myocardial enzymes. Tandem mass spectrometry screening showed significantly elevated C14, C14:1, C16:1, C16:2, C18 and C14/C8. Genetic testing revealed that he has harbored compound heterozygous variants of the ACADVL gene, namely c.664G>A (p.G222R) and c.1345G>A (p.E449K), which were respectively derived from his father and mother. The child was diagnosed with VLCADD cardiomyopathy type and deceased 2 weeks later. Literature review has identified 60 Chinese children with VLCADD. The clinical classifications were mainly cardiomyopathy type and liver disease type, which accounted for 73.3% (43/60). The combination of ACADVL gene variants were correlated with the clinical classifications of VLCAD. Children with one or two loss-of-function (LOF) mutations showed more severe clinical manifestation and a higher mortality. Cardiomyopathy type had the poorest prognosis, with a mortality rate of 76.9% (20/26). C14:1 may be used as an indicator for the diagnosis of VLCADD, but cannot be used for clinical subtyping and prognosis evaluation. The c.1349G>A (p.R450H) variant had the highest frequency among the Chinese patients, accounting for 10.8% (13/120).@*CONCLUSION@#The clinical classifications of VLCADD are strongly correlated with the prognosis, and LOF mutations are more common in those with severe clinical manifestations. c.1349G>A (p.R450H) may be the most common variant among the Chinese patients, and early screening and diagnosis can greatly improve the prognosis of patients.

Clinical characteristics and genetic counseling for a three-generation Chinese pedigree with recurrent fetal Kabuki syndrome due to variant of KDM6A gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a pregnant woman with a history of adverse pregnancy outcomes.@*METHODS@#A woman with an adverse history of pregnancies including one fetal demise and two induced abortions due to fetal diaphragmatic hernia and complex cardiac anomalies was selected as the study subject. Muscle tissue from the induced abortus was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing of the couple and other family members.@*RESULTS@#Genetic sequencing revealed that the fetus has harbored a frameshift variant of the KDM6A gene (NM_001291415.2), namely c.1228_1229del (p.Gln410GlufsTer2), which was inherited from the woman and her mother. The variant was unreported previously, and the woman was found to have short stature, sparse eyebrows in the outer third, peculiar facial features, but normal intelligence in addition with female congenital genital malformation, like incomplete vaginal septum, double cervix, double uterus, and unilateral ovary absence. mostly similar phenotypes observed in her mother.@*CONCLUSION@#The hemizygous c.1228_1229del variant of the KDM6A gene probably underlay the abnormalities in the fetus. All findings have enabled genetic counseling for this family featuring X-linked inheritance, and the woman had given birth to a healthy girl with appropriate prevention and intervention.

Guideline for the management path and quality control of breast cancer prevention and treatment in China's counties (2023 edition) / 中华肿瘤杂志

Breast cancer is the most common malignant tumor among women in China. In 2016, there were about 306 000 new cases of breast cancer in Chinese females. Of these, about 33% (100 400) occurred in rural areas. County-level (counties or county-level cities) hospitals are the first diagnosis units for most rural breast cancer patients and play an important role in cancer prevention, screening, maintenance treatment, rehabilitation, follow-up, and referral. Due to economic and geographical constraints, county-level hospitals are relatively deficient in medical equipment, health human resources, and drug accessibility. There is an imperative need for breast cancer prevention and management guidelines that are suitable for the actual situation in China's counties. Therefore, under the policy background of hierarchical diagnosis and treatment, the Chinese expert group formulated the "Guideline for the management path and quality control of breast cancer prevention and treatment in China's counties (2023 edition)", aiming to expand the availability of quality medical resources and ensure they are better distributed among regions, enhance the capacity for breast cancer prevention and treatment, so as to improve the prognosis and quality of life of patients in China's counties. This guideline provides path diagrams which are concise, unambiguous and easy to translate into clinical practice, as reference for clinicians in county-level hospitals.

Chinese expert consensus on the diagnosis and treatment for lateral lymph node metastasis of rectal cancer (2024 edition) / 中华胃肠外科杂志

Lateral lymph node metastasis (LLNM) is common in mid-low rectal cancer and is also a major cause of postoperative local recurrence. Currently, there is still controversy regarding the diagnosis and treatment of LLNM in rectal cancer. This consensus, based on the "Chinese Consensus on Diagnosis and Treatment of Lateral Lymph Node Metastasis in Rectal Cancer (2019 edition)," incorporates the latest domestic and international research findings and revises aspects related to the diagnosis, treatment strategies, follow-up, and management of recurrence of LLNM in rectal cancer. A total of 42 domestic colorectal cancer experts participated in this consensus. It proposes 18 consensus statements on the diagnosis and treatment of LLNM, using the evaluation criteria of the U.S. Preventive Services Task Force for grading recommendations. The aim is to standardize further the diagnostic criteria and treatment strategies for LLNM in rectal cancer. Unresolved issues in this consensus require further clinical practice and active engagement in high-quality clinical research to explore and address them progressively.

Mutation characteristics of angioimmunoblastic T-cell lymphoma: an analysis of 75 cases / 中华病理学杂志

Objective: To investigate the characteristics of gene mutations in angioimmunoblastic T-cell lymphoma (AITL). Methods: Seventy-five AITL cases diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from June 2021 to June 2023 were included. Their formalin-fixed and paraffin-embedded or fresh tissues were subject to targeted next generation sequencing (NGS). The sequencing data was collected, and the distribution and type of gene mutations were analyzed. Results: 492 potential driver mutations were identified in 74 out of the 84 genes. Targeted sequencing data for the 75 AITL patients showed that the genes with mutation frequencies of ≥10% were TET2 (89.3%), RHOA (57.3%), IDH2 (37.3%), DNMT3A (36.0%), KMT2C (21.3%), PLCG1 (12.0%), and KDM6B (10.7%). There were significant co-occurrence relationships between TET2 and RHOA, TET2 and IDH2, and RHOA and IDH2 gene mutations (P<0.05), respectively, while TET2 and KDM6B gene mutations were mutually exclusive (P<0.05). Conclusions: The study reveals the mutational characteristics of AITL patients using NGS technology, which would provide insights for molecular diagnosis and targeted therapy of AITL.

Adrenal cortical carcinoma in children: a clinicopathological analysis of 25 cases / 中华病理学杂志

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of adrenal cortical carcinoma (ACC) in children. Methods: Twenty-five children with ACC diagnosed in the Department of Pathology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from March 2014 to August 2022 were retrospectively analyzed. The related literature was reviewed. Results: A total of 25 children with ACC were collected, including 11 males and 14 females, with a male to female ratio of 1.0∶1.3. The patient ages ranged from 8 months to 14 years (median, 4 years). Eighteen cases with clinical data had functional tumors (18/22, 81.8%) presenting with virilization or precocious puberty (15/18), symptoms related to hypercortisolism (8/18) or endocrine symptoms mixed with both (5/18), while 3 cases (3/22, 13.6%) had unknown clinical data. The clinical manifestations of four patients with nonfunctional tumors were an abdominal mass and/or abdominal pain, walking instability and others. Grossly, the average maximum diameter of the tumor was 9.4 cm. Most of the tumors were nodular and partially encapsuled. The cut surfaces were gray or gray brown, soft with hemorrhage. Histologically, the tumor cells were diffusely distributed, separated by a vascular-rich network. The tumor cells were large, with distinct nucleoli, abundant eosinophilic or clear cytoplasm, and round or oval nuclei. The mitotic index was high, and atypical mitoses were common. Necrosis, calcification, capsule invasion or/and venous invasion were present. In some cases, the tumor invaded the surrounding soft tissues or kidneys. Immunohistochemically, the tumor cells were diffusely positive for syn and SF1 and focally positive for α-inhibin, Melan A and Calretinin, but negative for CgA. Ki-67 proliferation index ranged from 2%-90%. TP53 gene status was examined in 7 cases, in which mutations were detected in 4 cases. Follow-up data was obtained in 21 patients, among whom 18 received chemotherapy and 3 received radiotherapy. Distant metastasis occurred in 13 patients. Median progression-free survival (PFS) was 11.2 months and median overall survival (OS) was 54.7 months. Patients aged less than 5 years had a better prognosis for OS (P<0.05) than the older ones (≥5 years), but a similar PFS (P>0.05). Male patients and Ki-67 proliferation index <15% had a better prognosis tendency for OS, but there was no statistically significant difference (P>0.05). Conclusions: ACC in children is a rare, often functional tumor associated with Li-Fraumeni genetic syndrome and has a poor prognosis. Diagnosis and differential diagnosis require a combination of morphological, phenotypic and clinical analysis.

Clinicopathological study of epithelioid and spindle cell rhabdomysarcoma with EWSR1/FUS-TFCP2 fusion / 中华病理学杂志

Objective: To investigate the clinicopathological and genetic features of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion. Methods: The clinical, morphological and immunohistochemical features of 14 cases of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion diagnosed from January 2019 to December 2022 in the Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed. The cases were all subject to FISH or next generation sequencing for analysis of molecular genetic features. The literature was reviewed. Results: There were 5 males and 9 females, with the age at presentation ranging from 6 to 36 years (mean, 22 years). Tumors occurred in the head and neck (9 cases), pelvic region (2 cases), bladder (one case), right humerus (one case), and the abdominal wall, humerus and pubic at the same time (one case). Presenting symptoms varied by location but often included pain or discomfort. Most of the patients showed aggressive radiographic features with soft tissue extension. The tumors had a median size of 6.6 cm (range, 2-23 cm). The tumors were poorly defined and irregularly shaped. Microscopic examination showed diffuse proliferation of spindle or epithelioid cells. While morphologically high-grade tumors displayed obvious cytological atypia, a high mitotic count and tumor necrosis, low-grade tumors grew in sheets and fascicles composed of spindle, epithelioid cells with moderate or abundant amounts of eosinophilic cytoplasm, without pronounced cytological atypia. The tumor cells expressed Desmin, MyoD1, and Myogenin, as well as ALK, EMA, and CKpan. EWSR1/FUS-TFCP2 gene fusion was detected in 14 cases with next generation sequencing and confirmed by FISH. Six cases had EWSR1-TFCP2 fusions and 8 cases showed FUS-TFCP2 fusions. Follow-up information was available in 13 patients, ranged from 5 to 37 months. At the end of follow-up period, 7 patients died of the disease. Six patients were alive:two cases had local recurrences and metastases, two cases of recurrences, one case of metastasis and one case without recurrences and metastasis. Conclusions: Epithelioid and spindle cell rhabdomysarcomas with EWSR1-TFCP2 or FUS-TFCP2 fusion show a very aggressive clinical course, and more commonly occur in the head and neck. Their genetic hallmark is the presence of EWSR1/FUS-TFCP2 fusions. Familiarity with its clinicopathological characteristics is helpful in avoiding misdiagnoses.

SRF-rearranged cellular perivascular myoid tumor: a clinicopathological analysis of two cases / 中华病理学杂志

Objective: To investigate the clinicopathological features, immunophenotype, diagnosis and differential diagnosis of SRF-rearranged cellular perivascular myoid tumor. Methods: Two cases of SRF-rearranged cellular perivascular myoid tumor diagnosed in the Department of Pathology, Fudan University Shanghai Cancer Center from October 2021 to March 2022 were collected. Immunohistochemical staining, fluorescence in-situ hybridization (FISH) and next-generation sequencing (NGS) were performed, and the literature was reviewed. Results: Case 1, a 3-month-old boy presented with a painless tumor of the scalp, measuring about 2 cm in diameter. Case 2, a 3-year-old girl complained with a painless tumor of the knee, measuring approximately 1.5 cm in diameter. Microscopically, the tumor had a clear boundary and showed multinodular growth. The tumor was mainly composed of spindle cells arranged in long intersecting fascicles associated with thin, slit-like or branching ectatic vessels, focally forming hemangiopericytoma-like appearance. The tumor cells were abundant, but there was no obvious atypia. Mitotic figures (3-4/10 HPF) were noted. H-caldesmon and SMA were positive in both cases. Case 1 showed diffuse and strong positivity for Desmin, and focally for CKpan. Ki-67 proliferation index was 20% and 30%, respectively. FISH displayed NCOA2 gene translocation in case 1 and the RELA gene translocation in case 2. NGS detected the SRF-NCOA2 gene fusion in case 1 and the SRF-RELA gene fusion in case 2. Both patients underwent local excisions. During the follow-up of 5-14 months, case 1 had no local recurrence, while case 2 developed local recurrence 1 year post operatively. Conclusions: SRF-rearranged cellular perivascular myoid tumor is a novel variant of perivascular cell tumor, which tends to occur in children and adolescents. The tumor forms a broad morphologic spectrum ranging from a pericytic pattern to a myoid pattern, and include hybrid tumors with a mixture of pericytic and myoid patterns. Due to its diffuse hypercellularity and increased mitotic figures and smooth muscle-like immunophenotype, the tumor is easy to be misdiagnosed as myogenic sarcomas. The tumor usually pursues a benign clinical course and rare cases may locally recur.

Outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network / 中华儿科杂志

Objective: To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021. Methods: This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results: Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions: With the increasing number of extremely preterm infants at 22-25 weeks' gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.

Genetic and phenotypic analysis of MYO15A rare variants associated with autosomal recessive hearing loss / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze the phenotype and genotype characteristics of autosomal recessive hearing loss caused by MYO15A gene variants, and to provide genetic diagnosis and genetic counseling for patients and their families. Methods:Identification of MYO15A gene variants by next generation sequencing in two sporadic cases of hearing loss at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. The sequence variants were verified by Sanger sequencing.The pathogenicity of these variants was determined according to the American College of Medical Genetics and Genomics（ACMG） variant classification guidelines, in conjuction with clinical data. Results:The probands of the two families have bilateral,severe or complete hearing loss.Four variants of MYO15A were identified, including one pathogenic variant that has been reported, two likely pathogenic variants,and one splicing variant of uncertain significance. Patient I carries c. 3524dupA（p. Ser1176Valfs*14）, a reported pathogenic variant, and a splicing variant c. 10082+3G>A of uncertain significance according to the ACMG guidelines. Patient I was treated with bilateral hearing aids with satisfactory effect, demonstrated average hearing thresholds of 37.5 dB in the right ear and 33.75 dB in the left ear. Patient Ⅱ carries c. 7441_7442del（p. Leu2481Glufs*86） and c. 10250_10252del（p. Ser3417del）,a pair of as likely pathogenic variants according to the ACMG guidelines. Patient Ⅱ, who underwent right cochlear implantation eight years ago, achieved scores of 9 on the Categorical Auditory Performance-Ⅱ（CAP-Ⅱ） and 5 on the Speech Intelligibility Rating（SIR）. Conclusion:This study's discovery of the rare c. 7441_7442del variant and the splicing variant c. 10082+3G>A in the MYO15A gene is closely associated with autosomal recessive hearing loss, expanding the MYO15A variant spectrum. Additionally, the pathogenicity assessment of the splicing variant facilitates classification of splicing variations.

Association of stage 1 hypertension defined by the 2017 ACC/AHA guideline with cardiovascular events and mortality in Chinese adults / 中华医学杂志(英文版)

BACKGROUND@#The 2017 American College of Cardiology/American Heart Association (ACC/AHA) blood pressure (BP) guideline lowered the threshold defining hypertension to 130/80 mmHg. However, how stage 1 hypertension defined using this guideline is associated with cardiovascular events in Chinese adults remains unclear. This study assessed the association between stage 1 hypertension defined by the 2017 ACC/AHA guideline and clinical outcomes in the Chinese population.@*METHODS@#Participants with stage 1 hypertension ( n = 69,509) or normal BP ( n = 34,142) were followed in this study from 2006/2007 to 2020. Stage 1 hypertension was defined as a systolic blood pressure of 130-139 mmHg or a diastolic blood pressure of 80-89 mmHg. None were taking antihypertensive medication or had a history of myocardial infarction (MI), stroke, or cancer at baseline. The primary outcome was a composite of MI, stroke, and all-cause mortality. The secondary outcomes were individual components of the primary outcome. Cox proportional hazards models were used for the analysis.@*RESULTS@#During a median follow-up of 11.09 years, we observed 10,479 events (MI, n = 995; stroke, n = 3408; all-cause mortality, n = 7094). After multivariable adjustment, the hazard ratios for stage 1 hypertension vs. normal BP were 1.20 (95% confidence interval [CI], 1.13-1.25) for primary outcome, 1.24 (95% CI, 1.05-1.46) for MI, 1.45 (95% CI, 1.33-1.59) for stroke, and 1.11 (95% CI, 1.04-1.17) for all-cause mortality. The hazard ratios for participants with stage 1 hypertension who were prescribed antihypertensive medications compared with those without antihypertensive treatment during the follow-up was 0.90 (95% CI, 0.85-0.96).@*CONCLUSIONS@#Using the new definition, Chinese adults with untreated stage 1 hypertension are at higher risk for MI, stroke, and all-cause mortality. This finding may help to validate the new BP classification system in China.

Secular trends of asthma mortality in China and the United States from 1990 to 2019 / 中华医学杂志(英文版)

BACKGROUND@#Asthma imposes a large healthcare burden in China and the United States (US). However, the trends of asthma mortality and the relative risk factors have not been comparatively analyzed between the countries. The aim of this study was to compare the mortality and risk factors between China and the US.@*METHODS@#The deaths, and mortality rates of asthma in China and the US during 1990-2019 were obtained from the Global Burden of Disease Study 2019. The age-period-cohort model was used to estimate these mortality rates based on a log-linear scale with additive age, period, and cohort effects. The population attributable fractions of risk factors for asthma were estimated.@*RESULTS@#In 1990-2019, the asthma mortality rate was higher in China than in the US. The crude and age-standardized asthma mortality rates trended downward in both China and the US from 1990 to 2019. The decline in mortality was more obvious in China. Mortality gap between the two countries was narrowing. A sex difference in asthma mortality was observed with higher mortality in males in China and females in the US. The age effects showed that mortality increased with age in adults older than 20 years, particularly in the elderly. Downward trends were generally observed in the period and cohort rate ratios in both countries, with China experiencing a more obvious decrease. Smoking and high body mass index (BMI) were the leading risk factors for asthma mortality in China and the US, respectively. Mortality attributable to occupational asthmagens and smoking decreased the most in China and the US, respectively.@*CONCLUSIONS@#In 1990-2019, the asthma mortality rate was higher in China than in the US; however, the mortality gap has narrowed. Mortality increased with age in adults. The improvements in asthma death risk with period and birth cohort were more obvious in China than in the US. Smoking, high BMI, and aging are major health problems associated with asthma control. The role of occupational asthmagens in asthma mortality underscores the importance of management and prevention of occupational asthma.

Consensus on clinical application of immunoglobulin G4 / 中华内科杂志

IgG4 is a subclass of IgG. Elevated serum IgG4 levels are an important serological feature of IgG4 related diseases and serve as a serological marker for assessing disease activity and severity. The harmonization of IgG4 detection is crucial for its clinical application. National Clinical Research Center for Dermatologic and Immunologic Diseases (Peking Union Medical College Hospital), Experimental Diagnosis Research Committee, Rheumatology and Immunology Physicians Committee of Chinese Medical Doctor Association, Autoantibodies Detection Committee, and Chinese Rheumatism Data Center have organized clinical and laboratory experts to draft this consensus, aiming to standardize IgG4 detection and provide guideline for clinician and laboratory experts to appropriate utility and interpret IgG4 results in China.

Correlation between Combined Urinary Metal Exposure and Grip Strength under Three Statistical Models: A Cross-sectional Study in Rural Guangxi / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength.@*METHODS@#We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.@*RESULTS@#In the multimetal linear regression, Cu (β = -2.119), As (β = -1.318), Sr (β = -2.480), Ba (β = 0.781), Fe (β = 1.130) and Mn (β = -0.404) were significantly correlated with grip strength ( P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95% confidence interval: -1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn ( P interactions of 0.003 and 0.018, respectively).@*CONCLUSION@#In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Disease spectrum and pathogenic genes of inherited metabolic disorder in Gansu Province of China / 中国当代儿科杂志

OBJECTIVES@#To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder (IMD) among neonates in Gansu Province of China.@*METHODS@#A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021. A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.@*RESULTS@#A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates, and the overall prevalence rate of IMD was 0.63 (1/1 593), among which phenylketonuria showed the highest prevalence rate of 0.32 (1/3 083), followed by methylmalonic acidemia (0.11, 1/8 959) and tetrahydrobiopterin deficiency (0.06, 1/15 927). In this study, 166 variants were identified in the 28 pathogenic genes, with 13 novel variants found in 9 genes. According to American College of Medical Genetics and Genomics guidelines, 5 novel variants were classified as pathogenic variants, 7 were classified as likely pathogenic variants, and 1 was classified as the variant of uncertain significance.@*CONCLUSIONS@#This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities / 中国肺癌杂志

BACKGROUND@#In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration.@*METHODS@#A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases.@*RESULTS@#MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05).@*CONCLUSIONS@#The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.

Effectiveness Evaluation of Low-dose Spiral Computed Tomography for Lung Cancer Screening in Minhang District of Shanghai / 中国肺癌杂志

BACKGROUND@#Low-dose spiral computed tomography (LDCT) has been recommended for lung cancer screening in high-risk populations. However, evidence from Chinese populations was limited due to the different criteria for high-risk populations and the short-term follow-up period. This study aimed to evaluate the effectiveness in Chinese adults based on the Lung Cancer Screening Program in Minhang District of Shanghai initiated in 2013.@*METHODS@#A total of 26,124 subjects aged 40 years or above were enrolled in the Lung Cancer Screening Program during the period of 2013 and 2017. Results of LDCT examination, and screen-detected cancer cases in all participants were obtained from the Reporting System of the Lung Cancer Screening Program. The newly-diagnosed cases and their vital status up to December 31, 2020 were identified through a record linkage with the Shanghai Cancer Registry and the Shanghai Vital Statistics. Standardized incidence ratio (SIR) and 95%CI were calculated using the local population at ages of 40 or above as the reference. Proportions of early-stage cancer (stage 0-I), pathological types, and 5-year observed survival rates of lung cancer cases were estimated and compared between the cases derived from the screened and non-screened populations. Cox regression models were applied to evaluate the hazard ratio (HR) and 95%CI of LDCT screening with all-cause death of the lung cancer cases.@*RESULTS@#The crude and age-standardized incidence of lung cancer in screened population were 373.3 (95%CI: 343.1-406.1) and 70.3 per 100,000 person-years, respectively, with an SIR of 1.8 (95%CI: 1.6-1.9), which was observed to decrease with following-up time. The early-stage cancer accounted for 49.4% of all lung cancer cases derived from the screened population, significantly higher than 38.4% in cases from the non-screened population during the same period (P<0.05). The proportion of lung adenocarcinoma (40.7% vs 35.9%) and 5-year survival rate (53.7% vs 41.5%) were also significantly higher in the cases from the screened population (all P<0.05). LDCT screening was associated with 30% (HR=0.7, 95%CI: 0.6-0.8) reduced all-cause deaths of the cases.@*CONCLUSIONS@#The participants of the screening program are at high-risk of lung cancer. LDCT favors the early-detection of lung cancer and improves 5-year survival of the screened cases, indicating a great potential of LDCT in reducing the disease burden of lung cancer in Chinese populations.