Objective To observe the effect of Natural mountain spring on oxidative damage of aging mice . Methods Thirty male aging mice were randomly divided into experimental group ( drink Natural mountain spring ) and control group ( drink tap water ) according to the level of MDA .The serum in the two groups was taken for T-SOD activity and MDA content analysis after two months .Results The MDA content in experimental group decreased markedly than that in control group .Conclusion Natural mountain spring could alleviate oxidative damage by free radicals to extent .

Objective:To analyze the MRI characteristics of surgical resected renal angiomyolipoma (AML) smaller than 4 cm.Methods:A total of 112 patients with surgical pathology confirmed renal AML of which the maximum diameter was smaller than 4 cm were analyzed retrospectively in the First Medical Centre, Chinese PLA General Hospital from January 2014 to November 2020, 5 of which were epithelioid angiomyolipoma (EAML) patients. According to the presence or absence of visible fat in lesions on MRI, the lesions were divided into AML with fat group and AML without visible fat (AML wovf) group. The MRI features were evaluated, including maximum diameter, location, growth pattern, shape, beak sign, angular interface with renal parenchyma, pseudo-capsule, hemorrhage, cystic degeneration, coagulative necrosis, flowing void in the tumor, signal intensity and homogeneity on T 2WI and diffusion weighter imaging (DWI), the peak enhanced phase. The differences of maximum diameter of AML with fat and AML wovf were analyzed using Mann-Whitney U test, and the differences of MRI features were analyzed using χ 2 test or Fisher′s exact probability test. Results:There were 123 lesions found in 112 patients, and 96 lesions contained fat and 27 lesions were AML wovf. 82 lesions showed round and round-like shapes, 112 lesions showed exophytic growth pattern, 71 lesions with peak enhancement in corticomedullary phase. And the numbers of lesions with angular interface with renal parenchyma, beak sign, cystic degeneration, pseudo-capsule, hemorrhage were 30, 49, 1, 1, 1, respectively. There was no coagulative necrosis in all lesions. Compared with AML with fat, AML wovf was single lesion. The diameters of AML with fat and AML wovf were 2.5 (1.7, 3.5) and 1.8 (1.4, 2.3) cm respectively, with statistically significant difference ( Z=-2.80, P=0.005). In the AML with fat and AML wovf, 65 and 12 cases were heterogeneous in T 2WI, 44 and 5 lesions showed beak sign, 26 and 4 lesions showed angular interface with renal parenchyma, 57 and 10 cases were heterogeneous in DWI. And there were 5 and 6 lesions showed the endophytic, 44 and 8 lesions showed partly exophytic, 47 and 13 lesions showed exophytic in patterns of tumor growth respectively. The beak sign, homogeneous in T 2WI and DWI, patterns of tumor growth showed statistical differences in AML with fat and AML wovf (all P<0.05), and there was no significant difference in other features ( P>0.05). A total of 5 EAML patients were with 8 lesions. One patient had 4 lesions with fat, other patients had single lesion in which 2 lesions with fat, 2 lesions without visible fat. One lesion without visible fat showed hemorrhage. Conclusions:Surgical resected AML smaller than 4 cm is often exophytic round and round-like, enhanced in corticomedullary phase, showing angular interface with renal parenchyma and beak sign, with rare cystic degeneration, pseudo-capsule, hemorrhage and improbable coagulation necrosis. AML wovf is single smaller lesion which often shows endophytic growth pattern, and beak sign is infrequent. EAML seems to be present in two modes, multiple lesions with fat and AML wovf with hemorrhage.

Immunotherapy emerged as a paradigm shift in cancer treatments, which can effectively inhibit cancer progression by activating the immune system. Remarkable clinical outcomes have been achieved through recent advances in cancer immunotherapy, including checkpoint blockades, adoptive cellular therapy, cancer vaccine, and tumor microenvironment modulation. However, extending the application of immunotherapy in cancer patients has been limited by the low response rate and side effects such as autoimmune toxicities. With great progress being made in nanotechnology, nanomedicine has been exploited to overcome biological barriers for drug delivery. Given the spatiotemporal control, light-responsive nanomedicine is of great interest in designing precise modality for cancer immunotherapy. Herein, we summarized current research utilizing light-responsive nanoplatforms to enhance checkpoint blockade immunotherapy, facilitate targeted delivery of cancer vaccines, activate immune cell functions, and modulate tumor microenvironment. The clinical translation potential of those designs is highlighted and challenges for the next breakthrough in cancer immunotherapy are discussed.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with dyschromatosis symmetrica hereditaria (DSH). METHODS: PCR and Sanger sequencing were carried out for the proband, and suspected variant was validated by Sanger sequencing in the pedigree. RESULTS: The proband was found to harbor a novel variant of c.1352delA (p.N451Mfs*13) of the ADAR (NM_001111) gene. The same variant was found in her affected mother and sister, but not in her unaffected father, uncle, and 100 healthy individual. CONCLUSION The novel variant of the ADAR gene probably underlay the pathogenesis of DSH in this pedigree.
Adenosine Deaminase/genetics* ; China ; Female ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders/congenital* ; RNA-Binding Proteins/genetics*

OBJECTIVE: To analyze the clinical features and genetic variant in a patient with Usher syndrome. METHODS: Whole exome sequencing was carried out for the patient. Suspected variants were validated by Sanger sequencing of her parents and fetus. RESULTS: The proband was found to harbor compound heterozygous variants c.17_18insA (p.Tyr6Ter*) and c.4095_4096insA (p.Arg1366Lys fs*38) of the PCDH15 gene (NM_033056), which were respectively inherited from her father and mother. The same variants were not detected in 100 healthy controls. Based on the guidelines of the American Society of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PM2+PP4). By prenatal diagnosis, her fetus was found to carry the c.4095_4096insA variant. After birth, the child has passed neonatal hearing screening test, and no abnormal auditory and visual function was found after the first year. CONCLUSION The compound heterozygous variants c.17_18insA (p.Tyr6Ter*) and c.4095_4096insA (p.Arg1366Lys fs*38) of the PCDH15 gene probably underlay the Usher syndrome is this proband.
Cadherin Related Proteins ; Cadherins/genetics* ; Child ; China ; Female ; Genetic Testing ; Humans ; Infant, Newborn ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Usher Syndromes/genetics*

Objective:To investigate the clinical and MRI features of the mixed epithelial and stromal tumor family (MESTF) of the kidney.Methods:From January 2009 to September 2021, 42 patients with pathologically-proven MESTF from the First Medical Center of Chinese PLA General Hospital were collected in this retrospective study. Clinical information, MRI features, and pathological results were documented. According to the Bosniak classification (BC) version 2019, all MESTFs were divided into cystic MESTFs (36 cases) and solid-cystic MESTFs (6 cases). The R.E.N.A.L. nephrometry score (RNS), lesion size, laterality, location, margin, shape, growth pattern, presence of protruding into renal sinus, hemorrhage, and enhancement pattern were evaluated and documented. Based on BC versions 2005 and 2019, all the cystic MESTFs were assessed and divided into low (Ⅰ, Ⅱ, ⅡF) and high (Ⅲ, Ⅳ) grades. The independent sample t test or Mann-Whitney U test were performed to compare age, RNS, and lesion size between cystic MESTFs and solid-cystic MESTFs. Pearson χ 2 test, continuity-adjusted χ 2 test or Fisher exact probability test were utilized to evaluated the differences of clinical and MRI features and the distribution of low or high grades in two versions of BC. Results:Forty-two MESTFs were unilateral and solitary masses, 25 males and 17 females, with a mean age of (41±13) years old. Compared to solid-cystic MESTFs, cystic MESTFs were prone to demonstrate endophytic growth pattern (χ 2=17.77, P<0.001), and no significant differences in other clinical and MRI features were observed between cystic and solid-cystic MESTFs (all P>0.05). There were 7 low-grade and 29 high-grade tumors in the BC version 2005, respectively. Meanwhile, 24 low-grade and 12 high-grade tumors in the BC version 2019, respectively. The distribution of low or high-grade tumors in the two versions of BC had a statistically significant difference (χ 2=16.37, P<0.001). Conclusion:MESTFs demonstrated middle-age onset and no gender predilection. Cystic MESTFs are more likely to exhibit endophytic growth pattern with low-grade classification in BC system version 2019.

OBJECTIVETo investigate clinical and epidemiological characteristics of hospitalized severe acute respiratory illnesses (SARI) patients under 15 years old registered by sentinel hospitals at 10 cities and risk factors analysis of severe illness.

METHODSThe objects of this study were 2 937 SARI patients under 15 years old registered by sentinel surveillance in internal wards, pediatrics wards and intensive care units (ICU) of 10 sentinel hospitals in 10 cities during the period from December 2009 to June 2014. We also collected case report form (CRF) of them and their throat swabs for influenza testing. The inclusion criteria was hospitalized patients who were admitted by surveillance departments, registered by SARI surveillance system, under 15 years old, meeting SARI case definition and with complete CRF. Rank-sum test was used to compare the difference of age, the duration including from onset to admission, hospital stay and from onset to discharging/death between mild illness and severe illness. Chi-square test was used to compare the difference of demographic characteristics, influenza psoitive rate, vaccination rate of influenza, chronic medical conditions and clinical characteristics between mild illness and severe illness. Logistic regression was used to analysis risk factors associated with severe illness by two stratifications from SARI surveillance protocol (< 2 years old and ≥ 2 years old).

RESULTSAmong 2 937 SARI patients under 15 years old, 97.7% (2 872/2 937) was mild illnesses, and 2.3% (65/2 937) was severe illnesses. 78.8% (2 315/2 937) was under 5 years old. The median ages of severe illness and mild illness were 0.4 and 2.0 years old (U = -6.23, P < 0.001). The proportions of severe illness and mild illness with at least one chronic medical condition were 32.3% (21/65) and 8.4% (240/2 872) (χ² = 45.03, P < 0.001). The positive rate of influenza virus was 6.5% (190/2 937), which was 6.5% (186/2 858) for mild illness and 6.2% (4/65) for severe illness (χ² = 0.08, P = 0.961). The proportion of seasonal influenza vaccination was 1.5% (42/2 853), which was 1.5% (42/2 788) for mild illness and higher than that for severe illness (0) (χ² = 6.09, P = 0.048). For under 2 years old patients, age < 11 months and with at least one chronic medical condition were risk factors for severe SARI illness, and the risk for SARI patients who was 12-23 months and without medical condition was 14.71 (5.35-40.44) and 5.61 (2.96-10.63). For ≥ 2 years old patients, age, with at least one chronic medical condition and seasonal influenza vaccination history have no association with severe illness, OR (95% CI) was 0.92 (0.80-1.05), 0.67 (0.09-5.05) and 0.85 (0.31-2.35), respectively.

CONCLUSIONMost of SARI patients registered by 10 urban sentinel hospitals were patients under 5 years old. Age < 11 months and with at least chronic medical conditions were possible risk factors of severe illness of SARI patients.

Adolescent ; Child ; Child, Preschool ; China ; Chronic Disease ; Cities ; Hospitalization ; Hospitals ; Humans ; Infant ; Influenza, Human ; Orthomyxoviridae ; Respiratory Tract Diseases ; Risk Factors ; Sentinel Surveillance ; Vaccination

Objective:To explore the genetic etiology of fetuses with high suspicion of congenital skeletal malformation detected by prenatal ultrasound.Methods:This retrospective study collected 21 pregnant women with highly suspected fetal skeletal malformation indicated by ultrasound (the couples had no skeletal malformation) at Institute of Medical Genetics, Henan Provincial People's Hospital from January 2019 to August 2020. Amniotic fluid/umbilical cord blood of the fetus and peripheral blood of the couples were obtained for karyotype analysis, chromosomal microarray analysis, and whole-exome sequencing. Sanger sequencing was performed for the "pathogenic" "suspected pathogenic" "variants of uncertain significance" variants detected by whole exome sequencing. Genetic etiology of the 21 fetuses was described.Results:A total of five chromosomal abnormalities were detected, including four cases of trisomy 21 and one trisomy 18. Chromosome microarray analysis detected one case of abnormal copy number variation, 16 p11.2 microdeletion syndrome. Ten cases of monogenic diseases were found by whole exome sequencing and eight genes were involved ( SGMS2, FGFR3, DYNC2H1, WDR35, TBX5, COL2A1, FGFR2, and ALPL). Totally, 14 variations were detected, among which seven were novel variations (c.8129T>A, c.7126G>A, c.10307_10320del, and c.2641G>T in DYNC2H1 gene; c.3085G>A and c.491G>A in WDR35 gene; c.1070G>T in COL2A1 gene). Conclusions:For fetus, whose parents have no skeletal malformation, highly suspected of congenital malformation of skeletal system by prenatal ultrasound, genetic factor is the primary reason, including chromosomal abnormalities, copy number variations, and monogenic mutations.

Objective:To provide experimental evidence for genetic counseling and prenatal diagnosis by analyzing the clinical characteristics, screening and identification of the function of suspicious variants in a X-1inked spondyloepiphyseal dysplasia tarda (SEDT) family.Methods:The family members' medical history, general physical examination, femur, spine X-ray examination were collected. Peripheral blood samples of the family members were collected and DNA was extracted from these samples. Sequencing clinical whole exons of proband DNA by targeted gene high-throughput sequencing method, then analysis sequencing data. The suspicious mutation was confirmed in pedigree members by PCR and Sanger sequencing. Reverse transcription polymerase chain reaction (RT-PCR) experiments of total RNA from blood lymphocytes were performed. The amplification of exons 3 and 4 of the pathogenic gene were amplified and identified by agarose gel. The expression of the pathogenic gene was also detected.Results:Three affected males of the family were diagnosed with SEDT according to their clinical and radiological features. A nonsense mutation in the transport protein particle complex subunit 2 ( TRAPPC2) gene NM_001011658: c.91A>T (p.K31*) was found in the proband using whole exome sequencing. This variation was also detected in his cousin, but not in non-phenotypic members of the family. The RT-PCR result for amplification of exon 3 and 4 of peripheral blood lymphocytes was the same as those of normal controls, indicating that the mutation did not affect the splicing of transcripts. qPCR results showed that the transcriptional expression of TRAPPC2 in patients was significantly lower than that in family normal controls and normal people controls. Conclusion:Identification of the novel nonsense mutation (c.91A>T) in the SEDT family enables early patients screening, carrier detection, genetic counseling, prenatal diagnosis, and clinical prevention and treatment. The detailed genotype/phenotype descriptions contribute to the SEDT mutation spectrum. The study of the function of TRAPPC2 mutation will help to further elucidate the role of sedlin in cartilage.

Objective:To explore the value of whole exome sequencing for the inferential analysis of recessive genetic disease carrier status for couples with a child died of Primary immunodeficiency (PID).Methods:Clinical data was collected from four couples with a childbearing history of PID who had sought genetic counseling and undergone genetic testing at Henan Provincial People′s Hospital from February 2017 to December 2021. Whole exome sequencing (WES) was performed on both partners of each couple, and candidate variants were validated by Sanger sequencing and fluorescent quantitative PCR. Prenatal diagnosis was conducted on fetuses of these couples after confirming the variants.Results:A total of six variants were detected in four genes including IL2RG, BTK, CYBB, and DUOX2. Among these, the c.1265G>A and c.3329G>A variants of the DUOX2 gene and the c. 676C>T variant of the IL2RG gene were previously known as pathogenic variants. On the other hand, the Exon5_8del variant of the IL2RG gene, the c. 184_185delAC variant of the BTK gene, and the c. 472A>T variant of the CYBB gene were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics, the IL2RG: Exon5_8del, BTK: c. 184_185delAC and CYBB: c. 472A>T variants were classified as likely pathogenic (PVS1+ PM2_Supporting+ PP4).Prenatal diagnosis was conducted for three couples during their subsequent pregnancies, and the results revealed that the fetuses had the wild-type genotypes at the c. 184_185 position of the BTK gene, the c. 472 position of the CYBB gene, and the c. 676 position of the IL2RG gene. Follow-up examinations one year after birth has found no abnormality in the infants. Conclusion:WES is an important tool to infer and analyze the carryier status for couples who had given births to children died of PID and improve the positive detection rate.