[Pathogenic agents causing acute respiratory tract infections in pediatric patients in Spring, 2023, in Beijing].

Objective: To explore the pathogenic agents of acute respiratory infection (ARI) in children in Beijing. Methods: In the cross-sectional study, 3 groups of children from different departments were enrolled from Feb 6th, 2023 (6th week) to May 28th (21th week), 2023, including influenza-like case group from emergency department for nucleic acid testing of influenza virus (Flu) and human metapneumovirus (HMPV), the outpatient ARI group under nucleic acid testing for Flu, respiratory syncytial virus (RSV), adenovirus (ADV), and parainfluenza virus (PIV), and the inpatient ARI group under nucleic acid testing for Flu, RSV, HMPV, ADV, human bocavirus (HBoV), Rhinovirus (Rh), PIV, coronavirus (HCoV), Mycoplasma pneumoniae (Mp) and Chlamydia pneumonia (Cp). Results: There were 320 influenza-like cases enrolled, including 192 males and 128 females, aged 4.7 (3.6, 6.9) years, and 117 cases (36.6%) positive for Flu A, which contained similar proportion of pandemic H1N1 (H1N1) 47.0% (55/117) and H3N2 53.0% (62/117), and 13 cases for HMPV 4.1% (13/320). The rate of Flu reached its peak at the 10th week, with H1N1 as the predominant one from the 6th to 9th week (10.0%-50.0%) and then H3N2 from the 10th to 16th week (15.0%-90.0%). HMPV was detected from the 15th week 5.0% (1/20), and then reached to 30.0% (6/20) at the 20th week. In the outpatient ARI group, 7 573 were enrolled, including 4 131 males and 3 442 females, aged 4.0 (2.1, 5.3) years, and the highest positive rate for RSV 32.9% (2 491/7 573), followed by Flu A 12.1% (915/7 573). The dominant one was Flu A in weeks 6-14 (23.2%-74.7%), then RSV in the 15th week 24.8% (36/145). In the inpatient ARI group, 1 391 patients were enrolled, including 804 males and 587 females, aged 3.3 (0.4, 5.8) years, and the highest positive rate for Rh 18.7% (260/1 391), followed by RSV 12.4% (173/1 391), Flu A 10.2% (142/1 391, of which 116 cases (81.7%) were H1N1, and 26 cases (18.3%) were H3N2) and HMPV 3.1% (43/1 391). H1N1 was detected from the 7th week 10% (6/60), to peak in the 11th week 31.8% (21/66). H3N2 was detected from the 8th week 1.5% (1/68), and then kept in low level. The proportion of H1N1 among Flu was 81.7% (116/142) in the inpatient ARI group. RSV was detected from 12th week 1.3% (1/80), reaching 30.4% (35/115) at 19th week. The positive rate of HMPV reached 12.1% (14/116) at 21th week. Conclusions: In the spring of 2023, the first one in Beijing is the Flu epidemic, with H1N1 being the predominant one in the early stage and H3N2 in the later stage. Then, there is a postponed RSV epidemic and an increased HMPV detection. In addition, nucleic acid testing for outpatient children should be strengthened to provide early warning of epidemics.

Exotic Dark Matter Search with the CDEX-10 Experiment at China's Jinping Underground Laboratory.

A search for exotic dark matter (DM) in the sub-GeV mass range has been conducted using 205 kg day data taken from a p-type point contact germanium detector of the CDEX-10 experiment at China's Jinping underground laboratory. New low-mass dark matter searching channels, neutral current fermionic DM absorption (χ+A→ν+A) and DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), have been analyzed with an energy threshold of 160 eVee. No significant signal was found; thus new limits on the DM-nucleon interaction cross section are set for both models at the sub-GeV DM mass region. A cross section limit for the fermionic DM absorption is set to be 2.5×10^{-46} cm^{2} (90% C.L.) at DM mass of 10 MeV/c^{2}. For the DM-nucleus 3→2 scattering scenario, limits are extended to DM mass of 5 and 14 MeV/c^{2} for the massless dark photon and bound DM final state, respectively.

[Molecular epidemiology of norovirus associated with pediatric acute gastroenteritis in Beijing in 2020].

Objective: To investigate the molecular epidemiology of norovirus associated with pediatric acute gastroenteritis in Beijing under the Working Mechanism for Joint Prevention and Control of the Epidemic in 2020. Methods: This was a retrospective, repeated cross-sectional study. Fecal or vomit samples (1 213 cases) were collected from children visited the Capital Institute of Pediatrics Affiliated Children's Hospital for acute gastroenteritis from January 1 to December 31, 2020. First, real-time reverse PCR (RT-PCR) was used to screen the samples for norovirus, and then RdRp gene and capsid gene VP1 of norovirus-positive samples were amplified by conventional RT-PCR for genotyping based on the nucleotide sequence. The χ2 test was used to compare the positive rates and genotypes of norovirus among different specimen types, genders of children, and different age groups. Results: Among the 1 213 samples were collected, 215 samples were positive for norovirus, with a positivity rate of 17.7% for the whole year. The peak of norovirus infection observed mainly in the cold seasons, as the positive rates were 28.6% (18/63), 26.2% (16/61), 22.8% (77/338) and 17.1% (89/520) in January, October, November and December, respectively. The positive rate of norovirus in fecal sample was significantly higher than that in vomit sample (χ2 = 9.692, P<0.01). There was no significant difference between genders (χ2=0.041, P>0.05), but significant difference was found between age groups with the highest rate in the 6-48 months group (χ²=103.112, P<0.01). Three genogroups (GⅠ, GⅡ and GⅨ) of the circulating virus were detected by G-gene typing, and GⅡgenogroup was predominant, accounting for 98.5% (196/199). Among the GⅡ positive samples, genotype GⅡ.4 Sydney (55.1%, 108/196) was the most common, followed by GⅡ.2 (29.6%, 58/196), while the GⅡ.3 norovirus (10.2%, 20/196) which was common in previous years was not as much as before. Based on the P-type, GⅡ.P16 was predominant (61.5%, 96/156), followed by GII.P31 (19.9%, 31/156). The dual genotyping revealed that GⅡ.4 Sydney [P16] (36.4%, 56/154) and GⅡ.2 [P16] (24.7%, 38/154) were predominant. Conclusion: The prevalence of norovirus in children in 2020 in Beijing is not much different from those of the previous years, but the genotypes composition has changed significantly, and there are multiple genotypes circulating simultaneously.

[Investigation of pathogenic agents causing acute respiratory tract infections in pediatric patients in a children's hospital assigned for case screening in Beijing during the outbreak of COVID-19].

Objective: To investigate the spectrum of pathogenic agents in pediatric patients with acute respiratory infections (ARI) during the outbreak of coronavirus infectious diseases 2019 (COVID-19). Methods: Three groups of children were enrolled into the prospective study during January 20 to February 20, 2020 from Capital Institute of Pediatrics, including children in the exposed group with ARI and epidemiological history associated with COVID-19 from whom both pharyngeal and nasopharyngeal swabs were collected, children in the ARI group without COVID-19 associated epidemiological history and children in the screening group for hospital admission, with neither COVID-19 associated epidemiological history nor ARI. Only nasopharyngeal swabs were collected in the ARI group and screening group. Each group is expected to include at least 30 cases. All specimens were tested for 2019-nCoV nucleic acid by two diagnostic kits from different manufacturers. All nasopharyngeal swabs were tested for multiple respiratory pathogens, whilst the results from the ARI group were compared with that in the correspondence periods of 2019 and 2018 used by t or χ(2) test. Results: A total of 244 children were enrolled into three groups, including 139 males and 105 females, the age was (5±4) years. The test of 2019-nCoV nucleic acid were negative in all children, and high positive rates of pathogens were detected in exposed (69.4%, 25/36) and ARI (55.3%, 73/132) groups, with the highest positive rate for mycoplasma pneumoniae (MP) (19.4%, 7/36 and 17.4%, 23/132, respectively), followed by human metapneumovirus (hMPV) (16.7%, 6/36 and 9.8%, 13/132, respectively). The positive rate (11.8%, 9/76) of pathogens in the screening group was low. In the same period of 2019, the positive rate of pathogens was 83.7% (77/92), with the highest rates for respiratory syncytial virus (RSV) A (29.3%, 27/92), followed by influenza virus (Flu) A (H1N1) (19.6%, 18/92) and adenovirus (ADV) (14.1%, 13/92), which showed significant difference with the positive rates of the three viruses in 2020 (RSV A: χ(2)=27.346, P<0.01; FluA (H1N1): χ(2)=28.083, P<0.01; ADV: χ(2)=7.848, P=0.005) . In 2018, the positive rate of pathogens was 61.0% (50/82), with the highest rate for human bocavirus (HBoV) (13.4%, 11/82) and followed by ADV (11.0%, 9/82), and significant difference was shown in the positive rate of HBoV with that in 2020 (χ(2)=6.776, P=0.009). Conclusions: The infection rate of 2019-nCoV is low among children in Beijing with no family clustering or no close contact, even with epidemiological history. The spectrum of pathogens of ARI in children during the research period is quite different from that in the previous years when the viral infections were dominant. MP is the highest positively detected one among the main pathogens during the outbreak of COVID-19 in Beijing where there is no main outbreak area.

Direct Detection Constraints on Dark Photons with the CDEX-10 Experiment at the China Jinping Underground Laboratory.

We report constraints on the dark photon effective kinetic mixing parameter (κ) with data taken from two p-type point-contact germanium detectors of the CDEX-10 experiment at the China Jinping Underground Laboratory. The 90% confidence level upper limits on κ of solar dark photon from 205.4 kg-day exposure are derived, probing new parameter space with masses (m_{V}) from 10 to 300 eV/c^{2} in direct detection experiments. Considering dark photon as the cosmological dark matter, limits at 90% confidence level with m_{V} from 0.1 to 4.0 keV/c^{2} are set from 449.6 kg-day data, with a minimum of κ=1.3×10^{-15} at m_{V}=200 eV/c^{2}.

Search for Light Weakly-Interacting-Massive-Particle Dark Matter by Annual Modulation Analysis with a Point-Contact Germanium Detector at the China Jinping Underground Laboratory.

We present results on light weakly interacting massive particle (WIMP) searches with annual modulation (AM) analysis on data from a 1-kg mass p-type point-contact germanium detector of the CDEX-1B experiment at the China Jinping Underground Laboratory. Datasets with a total live time of 3.2 yr within a 4.2-yr span are analyzed with analysis threshold of 250 eVee. Limits on WIMP-nucleus (χ-N) spin-independent cross sections as function of WIMP mass (m_{χ}) at 90% confidence level (C.L.) are derived using the dark matter halo model. Within the context of the standard halo model, the 90% C.L. allowed regions implied by the DAMA/LIBRA and CoGeNT AM-based analysis are excluded at >99.99% and 98% C.L., respectively. These results correspond to the best sensitivity at m_{χ}<6 GeV/c^{2} among WIMP AM measurements to date.

Constraints on Spin-Independent Nucleus Scattering with sub-GeV Weakly Interacting Massive Particle Dark Matter from the CDEX-1B Experiment at the China Jinping Underground Laboratory.

We report results on the searches of weakly interacting massive particles (WIMPs) with sub-GeV masses (m_{χ}) via WIMP-nucleus spin-independent scattering with Migdal effect incorporated. Analysis on time-integrated (TI) and annual modulation (AM) effects on CDEX-1B data are performed, with 737.1 kg day exposure and 160 eVee threshold for TI analysis, and 1107.5 kg day exposure and 250 eVee threshold for AM analysis. The sensitive windows in m_{χ} are expanded by an order of magnitude to lower DM masses with Migdal effect incorporated. New limits on σ_{χN}^{SI} at 90% confidence level are derived as 2×10^{-32}∼7×10^{-35} cm^{2} for TI analysis at m_{χ}∼50-180 MeV/c^{2}, and 3×10^{-32}∼9×10^{-38} cm^{2} for AM analysis at m_{χ}∼75 MeV/c^{2}-3.0 GeV/c^{2}.

[Correlation between human bocavirus 2 infection in children and acute diarrhea in Beijing].

Objective: To investigate the relationship between human bocavirus 2 (HBoV2) infection and acute diarrhea in children younger than 5 years of age in a case-control study. Methods: This was a prospective case-control study. During May 2016 to December 2016, fecal specimens were collected from children ≤5 years of age with acute diarrhea who visited the Affiliated Children's Hospital of Capital Institute of Pediatrics (case group), or from children ≤5 years of age without diarrhea from Longtan Community Medical Service Center, Beijing (control group). The case group (n=240) and the control group (n=240) were divided into 8 age subgroups: ≤1 month old, >1-3 months old, >3-6 months old, >6-12 months old,>1-2 years old,>2-3 years old,>3-4 years old and >4-5 years old, and there were 30 cases in each age subgroup. The specimens were tested for 7 types of diarrhea-associated viruses, especially for HBoV2 by real-time PCR method. The HBoV2 viral load was predicted according to the cycle threshold (Ct). Finally, t-test was used to compare the differences between groups. Results: In the case group (n=240), the positive rate of norovirus was 16.7% (40 cases); rotavirus, 10.8% (26 cases); HBoV2, 7.5% (18 cases); adenovirus, 7.1% (17 cases); astrovirus, 6.3% (15 cases); parachovirus, 3.8% (9 cases); and Aich virus, 0.4% (1 case). The positive rates of HBoV2 in case group (7.5%, 18 cases) and control group (5.0%, 12 cases) showed no significant difference (χ(2)=1.280, P=0.258), as well as in different age groups (all P>0.05) . However, the mean viral load of the HBoV2 in the case group (1×10(9)copies/L with cycle threshold (Ct) 25.8) was higher than that of control group (1×10(5)copies/L with Ct 33.8), showing a significant difference (t=0.597, P=0.000). Conclusions: Norovirus and rotavirus are still the important viral pathogens in children with acute diarrhea. A higher load of HBoV2 may indicate a higher risk of acute diarrhea in children ≤5 years of age in Beijing.

[Pathogen spectrum in enteroviral infections among children in Beijing from 2010 to 2016].

Objective: To understand the epidemiological and etiological characteristics of enterovirus (EV)-associated diseases among children in Beijing from 2010 to 2016. Methods: This was a repeated cross-sectional study. The throat swabs were collected from children with probable EV-associated diseases at the Children' s Hospital Affiliated to Capital Institute of Pediatrics from 2010 to 2016. The samples were sent for pan-EV, enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) detection by real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR) . The viral types of non-EV-A71 and non-CV-A16 EV-positive samples were identified using modified RT-PCR and sequencing with CV-A6, EV-A/B group and 5 'UTR universal primers. The constituent ratios of the prevalence of different EV types in different age and gender groups were compared. Results: Of the 2 703 throat swabs, 1 992 (73.7%) samples were positive for EV, including EV-A71 (19.1%, 516/2 703), CV-A16 (24.3%, 658/2 703), CV-A6 (22.2%, 600/2 703), CV-A10 (4.5%, 122/2 703) and other types of EV (3.5%, 95/2 703). There was 1 case of EV-A71 and CV-A16 co-infection. The positive detection rate of EV-A group (excluding EV-A71, CV-A16, CV-A6 and CV-A10) increased from 11.3% (7/62) to 95.2% (59/62) after using the modified VP1-specific primers and PCR amplification conditions. During the period between 2010 and 2012, CV-A16 and EV-A71 predominated in EV-positive samples. However, CV-A6 accounted for 60.7% (68/112) in 2013, much higher than CV-A16 (23.2%, 26/112) and EV-A71 (12.5%, 14/112). In 2014, EVs were mainly of CV-A16 and EV-A71, but CV-A6 was the predominant type in 2015 (68.2%, 232/340) and in 2016 (38.6%, 151/391). The epidemic season of EVs was mostly from April to August, but CV-A6 showed a small epidemic peak from October to November. The male-to-female ratio of EV-positive patients was 1.50∶1, and EV-associated diseases mostly occurred in children under 5 years of age. Younger children were more susceptible to CV-A6 than to EV-A71 and CV-A16. Conclusions: From 2010 to 2016, there was a significant change in the spectrum of EVs in children with EV-associated diseases in Beijing. Since 2013, non-EV-A71 and non-CV-A16 increased, and CV-A6 gradually became one of the major pathogens of EV-associated diseases. The modified PCR primers and amplification conditions can effectively improve the reliability of test results.

Limits on Light Weakly Interacting Massive Particles from the First 102.8 kg×day Data of the CDEX-10 Experiment.

We report the first results of a light weakly interacting massive particles (WIMPs) search from the CDEX-10 experiment with a 10 kg germanium detector array immersed in liquid nitrogen at the China Jinping Underground Laboratory with a physics data size of 102.8 kg day. At an analysis threshold of 160 eVee, improved limits of 8×10^{-42} and 3×10^{-36} cm^{2} at a 90% confidence level on spin-independent and spin-dependent WIMP-nucleon cross sections, respectively, at a WIMP mass (m_{χ}) of 5 GeV/c^{2} are achieved. The lower reach of m_{χ} is extended to 2 GeV/c^{2}.

Peripheral Blood Leukocyte Telomere Length Is Associated with Age but Not Renal Function: A Cross-Sectional Follow-Up Study.

OBJECTIVES: We aimed to evaluate the relationship between baseline renal function and changes in telomere length in Han Chinese. METHODS: The telomere restriction fragment (TRF) length of leukocytes in the peripheral blood was measured in healthy volunteers recruited in 2014. The estimated glomerular filtration rate (eGFR) was calculated based on serum creatinine (Scr) and serum cystatin C (CysC)-eGFRcys and eGFRScr-cys through the Cockcroft-Gault formula (eGFRC-G) or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI / eGFRCKD-EPI) equation. The correlation between telomere length changes over time and renal function was analyzed. RESULTS: Leukocyte TRF lengths were negatively correlated to age (r = -0.393, p < 0.001) and serum CysC (r = -0.180, p < 0.01), while positively associated with eGFRCKD-EPI, eGFRC-G, eGFRcys, and eGFRScr-cys (r = 0.182, 0.122, 0.290, and 0.254 respectively, p < 0.01). The 3-year change of telomere length was 46 bp/years. When adjusted for age, the associations between telomere length changes and baseline, subsequent TRF lengths, and serum CysC were no longer present. No association was observed between TRF length changes and renal function. CONCLUSION: The rate of telomere length changes was affected by age and baseline telomere length. The telomere length changes might be important markers for aging.

Study of inactive layer uniformity and charge collection efficiency of a p-type point-contact germanium detector.

The characteristics of the surface inactive layer of a 1-kg-mass p-type point-contact germanium detector were studied. The thickness of the inactive layer and its uniformity on the top and lateral surfaces were measured. A charge collection efficiency function was developed according to the Monte Carlo simulation to describe the charge collection capacity along the depth within this inactive layer. In the energy range below 18keV, the surface, bulk, and total spectra of 57Co, 133Ba, 137Cs, and 60Co from simulations based on the charge collection efficiency function were well consistent with those from experiments.

Clinical features of eosinophilic gastroenteritis with ascites.

OBJECTIVE: The aim of this study was to evaluate the clinical features and treatment responses of eosinophilic gastroenteritis (EG) with ascites. METHODS: Clinical data were collected on 6 EG patients with ascites from 2000 to 2012. RESULTS: Six patients were included in this study, ranging in age from 15 to 30 years. Most had an acute onset (5/6). The clinical manifestations included abdominal pain (5/6), vomiting (4/6), and diarrhea (3/6). The absolute values and percentages of peripheral blood eosinophils (Eos) were significantly elevated in all patients. Erosive or ulcerative lesions were found on endoscopic examination of all patients (6/6). Eosinophilic inflitration was confirmed by endoscopic biopsies (4/6). Ultrasound or abdominal CT showed gastrointestinal wall thickening and peritoneal effusion (6/6). Ascites from the patients were analyzed. Eos were found in ascites by pathological examination in the majority (5/6). The symptoms and peripheral eosinophilia responded to glucocorticoid treatment (p < 0.05). All the patients had good outcomes. One female patient had a relapse, which responded to re-administration of glucocorticoid treatment. CONCLUSIONS: EG with ascites is more common in young patients, often presenting with non-specific symptoms. Typical clinical manifestations include acute onset, abdominal pain, and ascites. Eos in ascites and peripheral blood are the main diagnostic clues. Ultrasound and CT examinations are important to support the diagnosis of EG, and endoscopic biopsies can help to establish the diagnosis. Treatment with glucocorticoids is effective.

Histopathological and ultrastructural changes of lichen sclerosus et atrophicus on the vulva.

Studies of 82 skin specimens from 81 cases of lichen sclerosus et atrophicus (LSA) are reported. Typical LSA pathological changes showed atrophy of the epidermis, hydropic degeneration at the basal layer, and homogenization of the collagen fibers in the superficial dermis with inflammatory cell infiltration underneath. Ultrastructural changes showed intercellular spaces enlarged, particularly near basal cells. Some mitochondria were swollen and rough endoplasmic reticula were enlarged. Some basement membranes were thinner, collagen fibers of varying diameters were arranged in irregular shapes and the fine structures had become unclear and had sometimes even disappeared.

A research for the relationship between human papillomavirus and human uterine cervical carcinoma. II. Molecular genetic and ultrastructural study on the transforming activity of recombinant retrovirus containing human papillomavirus type 16 subgenomic sequences.

In order to elucidate the role of HPV-16 in the development of genital cancer, NIH3T3 cells were transfected by HPV-16 whole genome and its two early genes, E6-E7. Besides ordinary calcium phosphate/DNA coprecipitation technique, a newly designed recombinant retrovirus containing the HPV-16 genome or subgenomes was used to infect cells for transfer of the target genes. The transforming activities have been demonstrated to be most efficient when a bioengineering technique of this kind is used. HPV-16 DNA was proved to have transforming potential for NIH3T3 cells, and the DNA of HPV-16 was proved to undergo multisite integration into transformed cells and nude mice tumour cells. The E6-E7 open reading frames are sufficient for transforming NIH3T3 cells independently in vitro, which implies that E6-E7 open reading frames are transforming genes or even viral oncogenes of HPV-16. The RNA transcribed by the E6-E7 of HPV-16 was expressed in transformed cells and in tumour cells of nude mice. The use of a recombinant retrovirus for gene transfer in this study is much more efficient than that of calcium phosphate/DNA coprecipitation. The lack of a tissue-culture system suitable for HPV replication in vitro makes HPV gene recombination into a specially engineered retrovirus for viral-mediated gene transfer of particular significance for the possible application of viral carcinogenesis, both in vitro and in vivo, for basic and clinical research.

A research for the relationship between human papillomavirus and human uterine cervical carcinoma. I. The identification of viral genome and subgenomic sequences in biopsies of Chinese patients.

Biopsies from 318 cases with squamous cell carcinoma of the uterine cervix, 48 with cervical and vulvar condylomata, 14 with cervical intraepithelial neoplasia (CIN), 34 with chronic cervicitis and 24 with normal cervical epithelium were collected from different geographic regions with different cervical cancer mortalities. The DNA.DNA dot-blot and Southern blot hybridization results show that there is a close relationship between HPV-16 and the uterine cervical squamous cell carcinoma in China. One very interesting observation is that the finding of HPV-16-homologous DNA differs significantly among five geographic regions, and corresponds with the mortalities from cervical cancer of these five regions. HPV-11 was found mainly in benign lesions. The rate of detection of HPV-16 in Chinese women increased from 8.3% in normal cervical epithelium to 20% in chronic cervicitis, 28% in cervical condyloma, 50% in CIN and 60.4% in cervical cancer. It is suggested that HPV-16 infection may be an etiological factor in the development of human cervical carcinoma. From the results of Southern blot hybridization, it appeared that HPV-16 DNA had been integrated into the genome of the host cell in cervical cancer. Whereas the HPV-16 DNA sequence was only present as an episome in normal cervical epithelium and cervical benign lesions. The rate of occurrence of E6-E7 genes is the highest (88.9%) compared with that of other subgenomic fragments of HPV-16 in specimens of human cervical cancer in China. This implies that E6 and E7 may be the oncogenic genes of HPV-16 and play an important role in the carcinogenesis of human cervical epithelial cells. The amplification and rearrangement of the c-myc protooncogene are closely associated with the occurrence of cervical cancer. The results presented here revealed that the activated c-myc oncogene may cooperate with HPV-16 in the carcinogenic processes.