Objective To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS).Methods The pretreatment conditions of solid phase extraction(SPE)were op-timized by orthogonal experimental design and the surface water samples were concentrated and ex-tracted by Oasis? HLB and Oasis? MCX SPE columns in series.The extracts were separated by Kine-tex? EVO C18 column,with gradient elution of 0.1%formic acid aqueous solution and 0.1%formic acid methanol solution.Q-TOF-MS'fullscan'and'targeted MS/MS'modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion,prod-uct ion and retention times.Results The 34 emerging contaminants exhibited good linearity in the con-centration range respectively and the correlation coefficients(r)were higher than 0.97.The limit of de-tection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%.The intra-day precision was 0.78%-18.70%.The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected,with a concentration range of 1.93-157.71 ng/L.Conclusion The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.

Objective To investigate the effects of an adeno-associated virus(AAV2)vector expressing secretory transforming growth factor-β(TGF-β)type Ⅱ receptor(sTβRⅡ)extracellular domain-IgG2a Fc fusion protein(sTβRⅡ-Fc)on proliferation and migration of triple-negative murine breast cancer 4T1 cells in mice.Methods The pAAV-sTβRⅡ-Fc vector expressing sTβRⅡ-Fc fusion protein constructed by molecular cloning,the capsid protein-expressing vector pAAV2 and the helper vector were co-transfected into HEK 293T cells to prepare the recombinant AAV2-sTβRⅡ virus,which was purified by density gradient centrifugation with iodixanol.Western blotting was used to examine the effects of AAV-sTβRⅡ virus on Smad2/3 phosphorylation in 4T1 cells and on expression levels of E-cadherin,vimentin and p-Smad2/3 in 4T1 cell xenografts in mice.BALB/c mice bearing subcutaneous xenografts of luciferase-expressing 4T1 cells received intravenous injections of AAV-sTβRⅡ virus,AAV-GFP virus or PBS(n=6)through the tail vein,and the proliferation and migration of 4T1 cells were analyzed with in vivo imaging.Ki67 expression in the tumor tissues and sTβRⅡ protein expressions in mouse livers were detected with immunohistochemistry and immunofluorescence staining,and tumor metastases in the vital organs were examined with HE staining.Results The recombinant pAAV-sTβRⅡ-Fc vector successfully expressed sTβRⅡ in HEK 293T cells.Infection with AAV2-sTβRⅡ virus significantly reduced TGF-β1-induced Smad2/3 phosphorylation in 4T1 cells and effectively inhibited proliferation and lung metastasis of 4T1 xenografts in mice(P<0.05).In the tumor-bearing mice,intravenous injection of AAV-sTβRⅡ virus significantly increased E-cadherin expression,reduced vimentin and Ki67 protein expressions and Smad2/3 phosphorylation level in the tumor tissues(P<0.05 or 0.01),and induced liver-specific sTβRⅡ expression without causing body weight loss or heart,liver,spleen or kidney pathologies.Conclusion The recombinant AVV2 vector encoding sTβRⅡ extracellular domain is capable of blocking the TGF-β signaling pathway to inhibit the proliferation and lung metastasis of 4T1 cells in mice.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To investigate the effects of an adeno-associated virus(AAV2)vector expressing secretory transforming growth factor-β(TGF-β)type Ⅱ receptor(sTβRⅡ)extracellular domain-IgG2a Fc fusion protein(sTβRⅡ-Fc)on proliferation and migration of triple-negative murine breast cancer 4T1 cells in mice.Methods The pAAV-sTβRⅡ-Fc vector expressing sTβRⅡ-Fc fusion protein constructed by molecular cloning,the capsid protein-expressing vector pAAV2 and the helper vector were co-transfected into HEK 293T cells to prepare the recombinant AAV2-sTβRⅡ virus,which was purified by density gradient centrifugation with iodixanol.Western blotting was used to examine the effects of AAV-sTβRⅡ virus on Smad2/3 phosphorylation in 4T1 cells and on expression levels of E-cadherin,vimentin and p-Smad2/3 in 4T1 cell xenografts in mice.BALB/c mice bearing subcutaneous xenografts of luciferase-expressing 4T1 cells received intravenous injections of AAV-sTβRⅡ virus,AAV-GFP virus or PBS(n=6)through the tail vein,and the proliferation and migration of 4T1 cells were analyzed with in vivo imaging.Ki67 expression in the tumor tissues and sTβRⅡ protein expressions in mouse livers were detected with immunohistochemistry and immunofluorescence staining,and tumor metastases in the vital organs were examined with HE staining.Results The recombinant pAAV-sTβRⅡ-Fc vector successfully expressed sTβRⅡ in HEK 293T cells.Infection with AAV2-sTβRⅡ virus significantly reduced TGF-β1-induced Smad2/3 phosphorylation in 4T1 cells and effectively inhibited proliferation and lung metastasis of 4T1 xenografts in mice(P<0.05).In the tumor-bearing mice,intravenous injection of AAV-sTβRⅡ virus significantly increased E-cadherin expression,reduced vimentin and Ki67 protein expressions and Smad2/3 phosphorylation level in the tumor tissues(P<0.05 or 0.01),and induced liver-specific sTβRⅡ expression without causing body weight loss or heart,liver,spleen or kidney pathologies.Conclusion The recombinant AVV2 vector encoding sTβRⅡ extracellular domain is capable of blocking the TGF-β signaling pathway to inhibit the proliferation and lung metastasis of 4T1 cells in mice.

AIM: To explore the characteristics of astigmatism in preschool children before, during and after the COVID-19 epidemic, so as to provide a reference for further prevention and control of children's vision.METHODS: In the consecutive four years from January 2018 to December 2021, a retrospective analysis of vision data was conducted on 2 273 preschool children(4 546 eyes)younger than 4 years old who participated in children's vision screening test in Baiyun district, Guangzhou. They were divided into 1-year old group(ages<1-year old, 420 cases), 2-year old group(1-year ≤ ages <2-year, 543 cases), 3-year old group(2-year ≤ages <3-year, 614 cases), and 4-year old group(3-year ≤ ages<4-year, 696 cases)according to ages. The analysis included astigmatic degrees of children's eyes as well as their conditions of astigmatism.RESULTS: In 2018, the astigmatic degrees of the both eyes of 1-year-old group were higher than those of other groups(P<0.05). The binocular astigmatic degrees of the preschool children in four groups were obviously higher in 2020 than 2019(P<0.05), while they were significantly decreased in 2021 when compared with 2020(P<0.05). From 2019 to 2020, the increase of astigmatic degrees of the right eye is more considerable than the left eye of preschool children in those four groups(P<0.001). Furthermore, the morbidity of astigmatism basically echoes with the changing tendency of astigmatic degrees from 2018 to 2021.CONCLUSIONS: Preschool children in Baiyun district, Guangzhou, have the highest degree of astigmatism and the fastest progression rate within 1 year old. Before COVID-19 epidemic, the changes in astigmatism and prevalence were relatively stable; during COVID-19 epidemic, the astigmatism and prevalence increased significantly and the astigmatic degrees of right eye increased more than that of the left eye; after the normalization of epidemic prevention and control, the astigmatism and prevalence decreased significantly.

This study compared the effects of Curcuma longa before and after processing with vinegar on the rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation to reveal the mechanism of vinegar processing in improving the role of C. longa in soothing liver and relieving pain. The rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation was established according to the Preparation of the Animal Model of Dysmenorrhea(Draft) and the chronic unpredictable stress me-thod. The changes in the body weight, organ indexes, writhing latency, writhing score, and serum levels of six liver function indicators, sex hormones, pain factors, and blood rheological indicators were measured to evaluate the efficacy of C. longa processed with vinegar or not in treating dysmenorrhea in the rats with syndrome of liver depression and qi stagnation. Compared with the model group, the C. longa group(processed with vinegar or not) showed slow weight loss, increase in writhing latency, and decrease in writhing response(P<0.05). The inhibition rates on writhing in raw C. longa, vinegar-processed C. longa, and positive groups were 33.780%, 64.611%, and 62.466%, respectively. The significantly higher inhibition rate of the vinegar processing group indicated that vinegar-processed C. longa demonstrated more significant therapeutic effect. The vinegar-processed C. longa group showed lower levels of alanine aminotransferase(ALT), alkaline phosphatase(ALP), aspartate aminotransferase(AST), direct bilirubin(DBIL), and total bilirubin(TBIL) and higher level of albumin(ALB)(P<0.05), which indicated that vinegar processing enhanced the therapeutic effect of C. longa on liver injury. The serum levels of estradiol(E_2) and oxytocin(OT) were lower in the vinegar-processed C. longa group(P<0.05), indicating that the vinegar-processed C. longa could regulate the sex hormone levels, reduce the activity of uterine smooth muscle and contraction of uterus, and alleviate the symptoms of dysmenorrhea in rats. Moreover, the vinegar-processed C. longa group showed lower interleukin-6(IL-6) and arginine vasopressin(AVP) levels and higher beta-endorphin(β-EP) level(P<0.05), which indicated that vinegar-processed C. longa regulated the levels of pain factors to exert the pain-relieving effect. Drug intervention decreased the whole blood viscosity low-cut, medium-cut and high-cut values, plasma viscosity, whole blood reduction viscosity low-cut and high-cut values, erythrocyte cumulative pressure, and equation K value of erythrocyte sedimentation rate(P<0.05), and the vinegar-processed C. longa group outperformed other groups. This result indicated that vinegar processing enhanced the function of C. longa in improving the local blood rheology. C. longa processed with vinegar can enter the liver to relieve the da-mage to the heart, liver, kidney, and uterus, repair the liver function, and recover the sex hormone levels and immune function by regulating the levels of sex hormones and pain factors and improving the blood rheology. It activates the pain-relieving mechanism to relieve the pain, protect the liver, and fight inflammation, which is consistent with the theory that vinegar processing facilitates C. longa entering the liver to sooth liver and relieve pain.

An 18-day-old male infant was admitted to the hospital due to recurrent hyperkalemia for more than 10 days. The neonate had milk refusal and dyspnea. The blood gas analysis revealed recurrent hyperkalemia, hyponatremia and metabolic acidosis. Adrenocortical hormone replacement therapy was ineffective. Additional tests showed a significant increase in aldosterone levels. Family whole exome sequencing revealed that the infant had compound heterozygous in the SCNNIA gene, inherited from both parents. The infant was diagnosed with neonatal systemic pseudohypoaldosteronism type I. The infant's electrolyte levels were stabilized through treatment with sodium polystyrene sulfonate and sodium supplement. The infant was discharged upon clinical recovery. This study provides a focused description of differential diagnosis of salt-losing syndrome in infants and introduces the multidisciplinary management of neonatal systemic pseudohypoaldosteronism type I.
Infant ; Infant, Newborn ; Humans ; Male ; Pseudohypoaldosteronism/genetics* ; Hyperkalemia/etiology* ; Hyponatremia/diagnosis* ; Diagnosis, Differential

OBJECTIVE: To investigate the effect of hemoglobin (Hb) on the efficacy of chimeric antigen receptor T cell therapy (CAR-T) in patients with multiple myeloma (MM). METHODS: From June 2017 to December 2020, 76 MM patients who received CAR-T therapy in the Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, with complete clinical data and evaluable efficacy, were selected as the research objects. According to the receiver operating characteristic (ROC) curve, the best cut-off value was obtained. The patients were divided into groups on the basis of Hb 105.5 g/L as the cut-off value. The age, sex, serum calcium, β₂-microglobulin, serum creatinine, lactate dehydrogenase (LDH), and the influencing factors of CAR-T treatment efficacy in MM patients were analyzed. RESULTS: Hb was an influencing factor of efficacy. Univariate analysis showed that Hb, LDH, and albumin affected the efficacy of CAR-T therapy. Multivariate analysis showed that Hb ( OR=1.039, 95% CI: 1.002-1.078) and LDH ( OR=1.014, 95% CI: 1.000-1.027) were the influencing factors for the efficacy of CAR-T therapy. CONCLUSION The efficacy of CAR-T therapy in MM patients with low Hb is poor, and Hb is a factor affecting the efficacy of CAR-T therapy.
Humans ; Multiple Myeloma/drug therapy* ; Receptors, Chimeric Antigen ; Immunotherapy, Adoptive ; Treatment Outcome ; Hematologic Diseases

Proto-Oncogene Proteins c-akt ; TOR Serine-Threonine Kinases ; GTP-Binding Protein alpha Subunits, Gi-Go/metabolism*

Humans ; Brain Neoplasms/metabolism* ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioma/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; ATPases Associated with Diverse Cellular Activities/metabolism* ; Mitochondrial Proteins/metabolism* ; GTP-Binding Protein alpha Subunits/metabolism*