Background Previous research on chlorinated paraffins (CPs) in fine particulate matter (PM_2.5) has predominantly focused on short- and medium-chain chlorinated paraffins (SCCPs and MCCPs), and few studies could simultaneously determine short-, medium-, and long-chain chlorinated paraffins (LCCPs). Simultaneous extraction and determination of SCCPs, MCCPs, and LCCPs in PM_2.5 could provide technical support for their environmental monitoring and human health risk assessment. Objective To establish a method based on QUEChERS pretreatment method in conjunction with ultra-performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry for simultaneously determining the levels of SCCPs, MCCPs, and LCCPs in PM_2.5. Methods The extraction solvents, extraction salts, and extraction steps of a QuEChERS method were optimized. The extraction efficiencies of the target substances were compared under 4 extraction solvents [acetonitrile, dichloromethane, and n-hexane solvents in sequence; acetonitrile: dichloromethane: n-hexane = 1: 1: 2 (v/v/v) mixed solvent; 1% acetic acid-acetonitrile: dichloromethane: n-hexane = 1: 1: 1 (v/v/v) mixed solvent; acetonitrile: dichloromethane: n-hexane = 1: 1: 1 (v/v/v) mixed solvent], 2 dehydrated salts (anhydrous MgSO₄+NaCl and anhydrous Na₂SO₄+NaCl), 2 purification salts (C18 and PSA), and 4 vortex time (5, 7.5, 10, and 12.5 min) conditions. Then internal standard was utilized to estimate linear range and detection limit of the refined QuEChERS approach. Results The linearities of SCCPs, MCCPs, and LCCPs were good in the range of 10~1000 ng·mL⁻¹ with the correlation coefficients all greater than 0.96. The method detection limits (MDLs) ranged from 0.01 to 0.29 ng·m⁻³. The spiked recoveries of SCCPs, MCCPs, and LCCPs at the low, medium, and high concentrations were 77.38%-81.64%, 93.11%-99.78%, and 87.41%-101.39%, respectively, and the relative standard deviations (RSDs) were 2.90%-12.84%. This method was used to determine the CPs levels in 11 PM_2.5 samples from Shijiazhuang. The positive rates of ∑SCCPs, ∑MCCPs, and ∑LCCPs were all 100%, the concentration ranges were 0.24-2.18 ng·m⁻³ (mean 0.84 ng·m⁻³), 0.17-1.67 ng·m⁻³ (mean 0.70 ng·m⁻³), and 0.01-0.16 ng·m⁻³ (mean 0.04 ng·m⁻³), respectively, and the percentages to ΣCPs were 52.95%, 44.39%, and 2.66%, respectively. Conclusion The method established in this study is simple, time-saving, solvent saving, and can simultaneously detect SCCPs, MCCPs, and LCCPs in PM_2.5, which is suitable for the determination of PM_2.5 samples in large quantities, and can also provide a reference for the detection methods of other halogenated organic compounds in PM_2.5.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

AIM:To investigate the effects and mechanisms of curcumin on apoptosis of retinal ganglion cells(RGCs)in chronic ocular hypertension rats.METHODS:A total of 21 Spraque-Dawley(SD)rats were randomly divided into 3 groups with 7 rats in each group. The rat models of chronic ocular hypertension were established by cauterization of the superior scleral veins in the high intraocular pressure model group and the curcumin treatment group, and the sham operation group only cut the conjunctiva without the cauterization of the superior scleral veins; the rats in the curcumin treatment group were intragastrically treated with curcumin at a dose of 4mL/kg, and the rats in the sham operation group and the high intraocular pressure model group were treated with pure water at a dose of 4mL/kg for 3wk. After 3wk, HE staining was used to observe the morphological and pathological changes of retina, the number of RGCs and the thickness of ganglion cell layer(GCL)in each group of rats; TUNEL staining was used to observe the apoptosis of RGCs and retinal cells in each group of rats; the expression levels of glutamate-cysteine ligase modifier subunit(GCLM)and heme oxygenase-1(HO-1)in the retina of each group of rats were detected by real-time fluorescence quantitative PCR, immunohistochemical staining and Western blot.RESULTS:Compared with the sham operation group, the retinal morphology of rats in the high intraocular pressure model group and the curcumin treatment group was disorganized, the number of RGCs was reduced, the GCL was thinner, the apoptosis rate of RGCs and retinal cells increased, and the expression levels of GCLM and HO-1 increased. Compared with the high intraocular pressure model group, the retinal morphology of rats in the curcumin treatment group was basically normal, the number of RGCs increased, the GCL thickened, the apoptosis rate of RGCs and retinal cells decreased, and the expression levels of GCLM and HO-1 increased.CONCLUSION:Curcumin can inhibit the apoptosis of RGCs in the rat model of chronic ocular hypertension by up-regulating the expression of antioxidant genes GCLM and HO-1.

Abstract: Objective　To collect and organize malaria case data in Hubei Province from 2017 to 2021, compare and analyze the malaria epidemic characteristics on the before and after malaria elimination, and provide scientific support for Hubei Province to further optimize the comprehensive strategies to prevent re-transmission after the elimination of malaria. Methods The study was conducted by collecting the data of reported malaria cases of Hubei during 2017-2021 from the Infectious Disease Surveillance Reporting and Management System, and conducting the epidemiological characteristics of malaria on pre-elimination (2017-2019) and post-elimination (2020-2021). Results A total of 429 cases of imported malaria were reported in Hubei Province from 2017 to 2021, and the malaria epidemic showed an obvious trend of rising first and then falling. On the pre-malaria elimination, 374 malaria cases were reported, including 262 cases of P.falciparum (70.05%); on the post-malaria elimination, 55 malaria cases were reported, including 25 cases of P.falciparum (45.45%). There was a statistically significant difference in the proportion of infections caused by the four types of malaria parasites before and after the elimination of malaria (χ2=14.248, P<0.05). On the pre-malaria elimination, the peak of disease onset mainly occurred in January, July, and November; on the post-malaria elimination, the peak of disease onset mainly occurred in January to February, and December. Both before and after malaria elimination, the reported cases were mainly concentrated in Wuhan, Yichang, Huangshi, Xiangyang, Shiyan and Huanggang, but the range of cases showed a clear trend of narrowing. Before and after malaria elimination, malaria cases in Hubei Province were mainly among young and middle-aged males aged 30-49. The proportions of workers and migrant workers increased from 37.70% and 9.09% before the elimination to 50.91% and 18.18% after the elimination, respectively, with a statistically significant difference (χ2=17.839, P<0.05). The percentage of interval from onset of illness to initial diagnosis ≥ 5d decreased from 21.66% before the elimination to 10.91% after the elimination (χ2=6.448, P<0.05). The percentage of definitive diagnosis of malaria at initial diagnosis in town clinic increased from 18.18% before the elimination to 50.00% after the elimination. The proportion of malaria cases diagnosed by county-level medical institutions increased from 22.73% before the elimination to 34.55% after elimination. There was no statistically significant difference in the proportion of malaria cases diagnosed by medical institutions at all levels before and after the elimination of malaria (χ2=5.630, P>0.05). The proportion of cases with the interval between initial diagnosis and diagnosis within 24h increased from 43.85% before the elimination to 70.91% after the elimination. There was a statistically significant difference in the proportion of cases with the interval between initial diagnosis and diagnosis before and after the elimination of malaria (χ2=14.006, P<0.05). Before and after malaria elimination, all reported cases were mainly imported from African countries. Conclusions There are imported malaria cases reported every year in Hubei Province before and after the elimination of malaria, which poses a great challenge to the prevention of re-transmission. Therefore, it is necessary to strengthen the surveillance system, detect and standardize the treatment of imported malaria cases in a timely manner, conduct targeted retransmission risk surveys and assessments, and consolidate the achievements of malaria elimination.

OBJECTIVE: To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients. METHODS: Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH). RESULTS: Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression. CONCLUSION There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.
Chromosome Aberrations ; Humans ; In Situ Hybridization, Fluorescence ; Multiple Myeloma/genetics* ; Mutation

Background: At the therapeutic doses, diclofenac sodium (DFS) has few toxic side effects on mammals. On the other hand, DFS exhibits potent toxicity against birds and the mechanisms remain ambiguous. Objectives: This paper was designed to probe the toxicity of DFS exposure on the hepatic proteome of broiler chickens. Methods: Twenty 30-day-old broiler chickens were randomized evenly into two groups (n = 10).DFS was administered orally at 10 mg/kg body weight in group A, while the chickens in group B were perfused with saline as a control. Histopathological observations, serum biochemical examinations, and quantitative real-time polymerase chain reaction were performed to assess the liver injury induced by DFS. Proteomics analysis of the liver samples was conducted using isobaric tags for relative and absolute quantification (iTRAQ) technology. Results: Ultimately, 201 differentially expressed proteins (DEPs) were obtained, of which 47 were up regulated, and 154 were down regulated. The Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to screen target DEPs associated with DFS hepatotoxicity. The regulatory relationships between DEPs and signaling pathways were embodied via a protein-protein interaction network. The results showed that the DEPs enriched in multiple pathways, which might be related to the hepatotoxicity of DFS, were “protein processing in endoplasmic reticulum,” “retinol metabolism,” and “glycine, serine, and threonine metabolism.” Conclusions The hepatotoxicity of DFS on broiler chickens might be achieved by inducing the apoptosis of hepatocytes and affecting the metabolism of retinol and purine. The present study could provide molecular insights into the hepatotoxicity of DFS on broiler chickens.

Objective: To analyze the clinical and genetic characteristics of 33 children with congenital lipoid adrenal hyperplasia (CLAH) caused by StAR gene defects. Methods: The clinical, biochemical, genetic, and follow-up (until December 2021) data of 33 children diagnosed with CLAH from 2006 to 2021 were retrospectively analyzed in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Results: Of the 33 children with CLAH, 17 had a karyotype of 46, XX and 16 had a karyotype of 46, XY; 31 were female and 2 were male by social gender. Classic type and non-classic type were found in 30 and 3 children respectively. The age at diagnosis was 9.0 (3.0, 34.5) months. All the 30 cases with classic CLAH presented within the first year of life with skin hyperpigmentation (28 cases, 93%), vomiting and(or) diarrhea (19 cases, 63%), no increase in body weight (8 cases, 27%), elevated adrenocorticotropic hormone levels (21cases (70%)>275 pmol/L), decreased cortisol levels (47 (31,126) nmol/L), hyponatremia ((126±13) mmol/L), hyperkalemia ((5.7±1.1) mmol/L), and normal 17α-hydroxyprogesterone levels (30 cases, 100%). All these with classic CLAH exhibited female external genitalia. Three children with non-classic CLAH (including 2 cases of 46, XY and 1 case of 46, XX) also showed signs and symptoms of adrenal insufficiency, but 2 of them had an age of onset later than 1 year of age, including 1 case of 46, XY with male external genitalia and 1 case of 46, XX with female external genitalia. The other 46, XY patient with non-classic CLAH presented with adrenal insufficiency at 2 months of age, showing micropenis and hypospadias. In the 17 females with 46, XX, 4 older than 10 years of age showed spontaneous pubertal development. A total of 25 StAR gene pathogenic variants were identified in 33 patients, with p.Q258* (18/66, 27%), p.K236Tfs*47 (8/66, 12%) and p.Q77* (6/66, 9%) being the common variantion. Six novel variants were found, including c.358T>G, c.713_714del, c.125del, c.745-1G>A, c.179-2A>C, and exon 1 deletion. Conclusions: Patients with classic CLAH typically present with signs and symptoms of primary adrenal insufficiency in the early infancy period and female external genitalia. p.Q258*, p.K236Tfs*47 and p.Q77* are common variants in CLAH patients.
Adrenal Hyperplasia, Congenital/genetics* ; Adrenal Insufficiency ; Adrenocorticotropic Hormone ; Child, Preschool ; China ; Disorder of Sex Development, 46,XY ; Female ; Humans ; Hydrocortisone ; Hydroxyprogesterones ; Hyperplasia ; Infant ; Male ; Mutation ; Phosphoproteins/genetics* ; Retrospective Studies

Objective: To assess the risk of public health emergencies in Zhejiang Province, March 2021. Methods: An expert counsel was conducted to assess the risk of coronavirus disease 2019 ( COVID-19 ) , enteritis due to norovirus, chicken pox and influenza by professionals in Zhejiang CDC, based on the information from infectious disease and public health emergency surveillance in Zhejiang Province, domestic health administrative departments, World Health Organization, and European CDC. Results: In March 2021, the risk of imported COVID-19 epidemic will be high in Zhejiang Province, and the possibility of local spread could not be ruled out. The possibility of a large-scale outbreak of enteritis due to norovirus and a small-scale outbreak of chickenpox in schools and kindergartens could not be ruled out after the new term begins. An increased risk of influenza epidemic is predicted in collective units such as schools and kindergartens, yet the risk of a large-scale one will be low. Conclusion High attention should be paid to COVID-19 and enteritis due to norovirus, and general attention should be paid to chicken pox and influenza outbreak.

Aim To explore the mechanism of hepatocellular carcinoma (HCC) resistance to aspirin and its anti-cancer effect, so as to provide new ideas and potential possibilities for clinical prevention and treatment. Methods The HCC rat model was induced by diethylnitrosamine (DEN). The pathological changes of rat liver were observed by HE staining. The expressions of AMPK, LC3, mTOR, Beclin-1, and TFEB proteins were detected by Western blot. HCC cell proliferation was detected by CCK8 assay. Apoptosis were measured by immunofluorescence assay. Results Aspirin significantly inhibited the development of DEN-induced hepatocellular carcinoma and decreased liver/body weight ratio compared with model group. Aspirin significantly increased the expressions of LC3, Beclin-1, TFEB and AMPK. The combination of aspirin and AMPK inhibitor significantly inhibited HCC cell proliferation and increased HCC cell apoptosis. Conclusions The combination of aspirin and AMPK inhibitor can significantly enhance the inhibitory effect of aspirin on HCC.

Objective:To retrospectively analyze the clinical outcomes of single unrelated cord blood transplantation (UCBT) in children with high risk and refractory acute myeloid leukemia (AML) .Methods:Between June 2008 and December 2018, a total of 160 consecutive pediatric patients with AML received single UCBT (excluding acute promyelocytic leukemia) . Myeloablative conditioning (MAC) regimen were applied. All patients received a combination of cyclosporine A (CsA) and mycophenolate mofetil (MMF) for the prophylaxis of graft -versus- host disease (GVHD) .Results:The cumulative incidence of neutrophil cells engraftment at day +42 and platelet recovery at day +120 was 95.0% (95% CI 90.0%-97.5%) at a median of 16 days after transplantation (range, 11-38 days) and 85.5% (95% CI 83.3%-93.4%) with a median time to recovery of 35 days (range, 13-158) , respectively. Incidence of grades Ⅱ-Ⅳ and Ⅲ-Ⅳ acute GVHD and chronic GVHD were 37.3% (95%CI 29.3%-45.2%) , 27.3% (95% CI 20.0%-35.0%) and 22.4% (95% CI 15.5%-28.7%) , respectively. The transplant-related mortality (TRM) at 360 day was 13.1% (95% CI 8.4%-18.9%) . The 5-year cumulative incidence of relapse was 13.8% (95% CI 8.5%-20.3%) . The 5-year disease-free survival (DFS) and overall survival (OS) were 71.7% (95% CI 62.7%-77.8%) and 72.2% (95% CI 64.1%-78.7%) , respectively. The 5-year GVHD and relapse free survival (GRFS) was 56.1% (95% CI 46.1%-64.9%) . The 5-year cumulative recurrence rates of CR1, CR2, and NR groups were 5.3%, 19.9%, and 30.9% ( P=0.001) , and the 5-year OS rates were 79.9% (95% CI 70.3%-86.7%) , 71.1% (95% CI 50.4%-84.4%) and 52.9% (95% CI 33.0%-69.3%) ( χ2=7.552, P=0.020) , respectively. Conclusions:For pediatric patients with high risk and refractory AML, UCBT is a safe and effective treatment option, and it is favorable to improve the survival rate in CR1 stage.