Objective:To evaluate the optimization effects of serratus anterior plane block (SAPB) combined with general anesthesia for thoracoscopic surgical ablation of atrial fibrillation (TSAAF).Methods:Eighty American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients of either sex, aged >18 yr, with a body mass index of 18-30 kg/m 2, scheduled for elective TSAAF, were randomly assigned to either SAPB combined with general anesthesia group (SG group) or general anesthesia group (G group), with 40 cases in each group. SG group received ultrasound-guided bilateral SAPB with 0.375% ropivacaine 20 ml each before surgery, while G group did not receive block before operation. Both groups underwent general anesthesia. The time to the first analgesia pump use, the number of successfully delivered doses and requirement for rescue analgesia within 48 h after operation were recorded. Inspiratory spirometry was measured at preoperative day 1 (T 0), at the time of discharge from the recovery room (T 1), and at 24 and 48 h after operation (T 2, 3). The extubation time was also recorded. The usage of intraoperative remifentanil, norepinephrine and ephedrine, duration of recovery room stay, and occurrence of recurrent atrial fibrillation, delirium, respiratory depression, and nausea/vomiting within 48 h after operation, and length of postoperative hospital stay were recorded. Results:Compared to G group, the time to the first analgesia pump use was significantly prolonged, the number of successfully delivered doses was reduced within 48 h after operation, the rate of rescue analgesia was decreased, inspiratory spirometry was increased at T 1-3, the extubation time and length of postoperative hospital stay were shortened, and the recurrence rate of atrial fibrillation was decreased within 48 h after surgery in SG group ( P<0.05). No significant differences were found between the two groups regarding the intraoperative remifentanil consumption, usage rate of vasoactive drugs, and incidence of postoperative nausea/vomiting, delirium and respiratory depression ( P>0.05). Conclusions:Combination of SAPB and general anesthesia can effectively improve the postoperative analgesic effect and is helpful for the recovery in the patients undergoing TSAAF.

OBJECTIVE: To explore the clinical phenotype and genetic features of a child with dilated cardiomyopathy (DCM). METHODS: Clinical data of the child who had presented at the Zhengzhou Children's Hospital on April 28, 2020 was collected. Trio-whole exome sequencing (trio-WES) was carried out for the child and her parents, and candidate variants were validated by Sanger sequencing. "FHL2" was taken as the key word to retrieve related literature from January 1, 1997 to October 31, 2021 in the PubMed database and was also searched in the ClinVar database as a supplement to analyze the correlation between genetic variants and clinical features. RESULTS: The patient was a 5-month-old female infant presented with left ventricular enlargement and reduced systolic function. A heterozygous missense variant c.391C>T (p.Arg131Cys) in FHL2 gene was identified through trio-WES. The same variant was not detected in either of her parents. A total of 10 patients with FHL2 gene variants have been reported in the literature, 6 of them had presented with DCM, 2 with hypertrophic cardiomyopathy (HCM), and 2 with sudden unexplained death (SUD). Phenotypic analysis revealed that patients with variants in the LIM 3 domain presented hypertrophic cardiomyopathy and those with variants of the LIM 0~2 and LIM 4 domains had mainly presented DCM. The c.391C>T (p.Arg131Cys) has been identified in a child with DCM, though it has not been validated among the patient's family members. Based on the guidelines of the American College of Medical Genetics and Genomics, the c.391C>T(p.Arg131Cys) variant was re-classified as likely pathogenic (PS2+PM2_Supporting+PP3+PP5). CONCLUSION The heterozygous missense variant of c.391C>T (p.Arg131Cys) in the FHL2 gene probably predisposed to the DCM in this child, which has highlighted the importance of WES in the clinical diagnosis and genetic counseling.
Female ; Humans ; Cardiomyopathy, Dilated/genetics* ; Cardiomyopathy, Hypertrophic ; Genetic Counseling ; Genomics ; Heterozygote ; Muscle Proteins/genetics* ; Transcription Factors ; LIM-Homeodomain Proteins/genetics*

BACKGROUND: Ischemic acute kidney injury (AKI) is a common syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathogenesis of ischemic AKI remains incompletely understood, and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking. Here, this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing (scRNA-seq) analysis in kidneys. METHODS: In this study, scRNA-seq technology was applied to kidneys from two ischemic AKI patients, and three human public scRNA-seq datasets were collected as controls. Differentially expressed genes (DEGs) and cell clusters of kidneys were determined. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as the ligand-receptor interaction between cells, were performed. We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion (I/R) injury induced AKI mice through immunohistochemistry staining. RESULTS: 15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control. The injured proximal tubules (PT) displayed a proapoptotic and proinflammatory phenotype. PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47 , RASSF4 , EBAG9 , IER3 , SASH1 , SEPTIN7 , and NUB1 , which have not been reported in ischemic AKI previously. Several hub genes were validated in kidneys from human AKI and renal I/R injury mice, respectively. Furthermore, PT highly expressed DEGs enriched in endoplasmic reticulum stress, autophagy, and retinoic acid-inducible gene I (RIG-I) signaling. DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, estrogen signaling, interleukin (IL)-12 signaling, and IL-17 signaling. Overexpressed genes in kidney-resident immune cells including macrophages, natural killer T (NKT) cells, monocytes, and dendritic cells were associated with leukocyte activation, chemotaxis, cell adhesion, and complement activation. In addition, the ligand-receptor interactions analysis revealed prominent communications between macrophages and monocytes with other cells in the process of ischemic AKI. CONCLUSION Together, this study reveals distinct cell-specific transcriptomic atlas of kidney in ischemic AKI patients, altered signaling pathways, and potential cell-cell crosstalk in the development of AKI. These data reveal new insights into the pathogenesis and potential therapeutic strategies in ischemic AKI.
Humans ; Mice ; Animals ; Transcriptome/genetics* ; Ligands ; Kidney/metabolism* ; Acute Kidney Injury/metabolism* ; Ischemia/metabolism* ; Reperfusion Injury/metabolism* ; Sequence Analysis, RNA ; Adaptor Proteins, Signal Transducing/metabolism* ; Tumor Suppressor Proteins/metabolism*

Objective:To investigate the association between relative mitochondrial DNA copy number (mtDNA-CN) and coal-burning-borne endemic fluorosis (abbreviated as coal-burning-borne fluorosis).Methods:From June 2018 to March 2019, using cross-sectional study, 482 patients with coal-burning-borne fluorosis were selected as the case group in Bijie City, a typical coal-burning-borne fluorosis area of Guizhou Province; meanwhile, 212 healthy individuals from Changshun County, a non-coal-burning-borne fluorosis area in Guizhou Province, were selected as the control group. Questionnaire survey and physical examination were used to collect general condition such as basic information and living habits of the two groups, peripheral venous blood samples were collected, and real-time fluorescence quantitative PCR was used to detect the relative mtDNA-CN in peripheral blood. The correlation between relative mtDNA-CN and coal-burning-borne fluorosis was analyzed by binary and unordered multi-class logistic regression.Results:There were significant differences in the body mass index (BMI), and the distribution of gender rario, marital status and education level between the control group and the case group ( t = 7.91, χ 2 = 5.11, 13.33, 34.32, P < 0.05). The relative mtDNA-CN in the control group was higher than that in the case group [median (quartile): 202 (138, 292) vs 131 (96, 217), Z = - 7.80, P < 0.001]. The results of binary logistic regression analysis [odds ratio (95% confidence interval)] showed that educational level [primary school: 0.572 (0.377 - 0.868), junior high school and above: 0.292 (0.174 - 0.493)], relative mtDNA-CN [131 - < 217: 0.265 (0.144 - 0.488), ≥217: 0.183 (0.100 - 0.335)] and BMI [1.222 (1.142 - 1.307)] were the influencing factors for the risk of coal-burning-borne fluorosis( P < 0.05). In subgroups with different BMI and educational levels, the relative mtDNA-CN was significantly negatively correlated with the risk of coal-burning-borne fluorosis( Ptrend < 0.05), and there was no interaction between mtDNA-CN and BMI and educational levels ( Pinteraction > 0.05). The results of unordered multi-class logistic regression analysis showed that the relative mtDNA-CN were significantly negatively correlated with the risk of dental fluorosis and skeletal fluorosis ( Ptrend < 0.05). Conclusion:The higher the relative mtDNA-CN, the lower the risk of coal-burning-borne fluorosis, suggesting that mtDNA-CN may be a potential biomarker of coal-burning fluorosis.

Objective:To explore the relationship between children's intelligence and urinary fluoride in Suojia Township of Miao, Yi and Hui Nationalities (referred to as Suojia Township), a coal-burning-borne endemic fluorosis area in Guizhou Province.Methods:In April 2019, 173 children aged 10 to 13 years old were selected from three schools in Suojia Township. According to whether they had dental fluorosis, the children were divided into case group ( n = 104) and control group ( n = 69). Middle segment urine samples of the children were collected and urinary fluoride level was determined by the method of ion-selective electrode. Combined Raven's Test-the Rural in China (CRT-RC2) was used for children's intelligence quotient (IQ) test. Linear regression analysis was used to observe the association between urinary fluoride and IQ, and the results were expressed by regression coefficient ( β) and 95% confidence interval ( CI). Results:Urinary fluoride level of case group was higher than that of control group [(2.14 ± 1.78) vs (1.53 ± 0.98) mg/L], and IQ was lower than that of control group [(92.33 ± 11.68) vs (100.38 ± 11.87) points], and the differences were statistically significant ( t = 2.58, 4.41, P < 0.05). The linear regression equation of urinary fluoride ( X) and IQ ( Y) of case group was Y = 96.99 - 2.86 X. For every 1 mg/L increase in urinary fluoride level, IQ decreased by 2.86 points ( β = - 2.86, 95% CI: - 5.48 - - 0.24). Conclusion:Long-term exposure to fluoride pollution from coal burning may damage children's intelligence, and children's IQ decreases with increase of fluoride level in urine.

Objective:To observe the effects of bilateral thoracic paravertebral block (TPVB) on left ventricular myocardial work using pressure-strain loop(PSL) in patients before off-pump coronary artery bypass graft(OPCABG).Methods:A total of 24 patients with coronary heart disease undergoing selective OPCABG were recruited in the First Affiliated Hospital of Nanjing Medical University from May to August 2021. All patients underwent ultrasound-guided TPVB preoperatively. Left ventricular global work, including global longitudinal strain(GLS), global work index(GWI), global constructive work(GCW), global waste work(GWW), global work efficiency(GWE), and regional work, including myocardial work index(MWI), myocardial work efficiency(MWE) were observed before TPVB and 20 minutes after TPVB.Results:The parameters of heart rate and left ventricular outflow tract blood flow were decreased [(69.13±10.72)bpm vs (65.46±9.66)bpm, P=0.010; (13.86±2.83)ml vs (12.72±2.60)ml, P=0.017]. The MWI in regional segments of hypokinesis and akinesis were significantly improved [hypokinesis: (1 175.76±206.64)mmHg% vs (1 349.38±462.35)mmHg%, P=0.004; akinesis: (684.94±251.39)mmHg% vs (965.35±384.33)mmHg%, P=0.001] and the MWE in regional segments of hypokinesis and akinesis were improved [hypokinesis: (87.79±7.46)% vs (90.35±6.39)%, P=0.029; akinesis: (70.24±18.03)% vs (80.15±16.65)%, P=0.021]. There were no significant changes in MWI, MWE, LVEF, GLS, GWI, GCW, GWW and GWE(all P>0.05). Conclusions:Based on PSL, the changes of left ventricular work in patients with OPCABG before and after TPVB show that TPVB can improve the blood supply of the ischemic myocardium, which provides a reliable basis for optimizing the perioperative anesthesia management.

Objective:To explore the feasibility of using the sigma metrics calculated with the data of internal quality control for the comparison of the analytical performance between different biochemical analyzers.Methods:The internal quality control results of twenty-five biochemical assays in the biochemical analyzers of the department of clinical laboratory in Cancer Hospital from February 1, 2021 to July 31, 2021 were collected. The formula sigma =( TEa- Bias)/ CV was used to calculate the sigma metrics of two different levels of the biochemical assays including albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, calcium, cholesterol, creatine kinase, chlorine, creatinine, γ- glutamyltranspeptidase, blood glucose, high density lipoprotein cholesterol, immunoglobulin A, immunoglobulin G, immunoglobulin M, potassium, lactate dehydrogenase, low density lipoprotein cholesterol, sodium, inorganic phosphorus, total bilirubin, triglyceride, total protein, urea, uric acid. The imprecision was obtained by the coefficient of variation of internal quality control. The bias was calculated by the deviation between the mean of internal quality control of the comparison instrument and the target instrument. The allowable total error ( TEa) was based on People's Republic of China Health Industry Standard (WS/T403-2012) or EQA standard of National Center for Clinical Laboratories (NCCL). Compared the sigma values of the comparison instrument relative to the target instrument with the average percentage bias obtained by the traditional comparison method. Quality goal index was used to analyze the causes of poor performance and judge the results of comparison. Results:Compared with the target instrument Beckman AU5800-3, the comparison instrument Beckman AU5800-1 had 10 assays with σ>6, accounting for 40%, 23 assays with σ>3, accounting for 92%, and only albumin and blood glucose showed σ<3. Through statostical analysis, the comparisons of all assays were passed. The comparison instrument Beckman AU5800-2 had 8 assays with σ>6, accounting for 32%, 20 assays with σ>3, accounting for 80%. Only alkaline phosphatase, calcium, lactate dehydrogenase, total protein and urea showed σ<3. Through statostical analysis, the comparisons of GGT and IgM failed. For the traditional comparison method, the percentage bias between the comparison instruments and the target instrument were all within the range of the evaluation standard. But there was no significant correlation between the σ value and the average bias of the traditional comparison method, and the biases were correlated.Conclusions:Using the sigma metrics calculated with the data of internal quality control for the comparison of different detection systems is a convenient and operable method. It can monitor the comparability between different detection systems in the laboratory at any time and be the supplement of the traditional comparison method.

Langerhans cell histiocytosis(LCH)and Langerhans cell sarcoma(LCS)are characterized by clone proliferation of Langerhans-type cells, which may occur concurrently or sequentially with T-cell acute lymphoblastic leukemia (T-ALL) and other Lymphoid neoplasms. A 15-year old female patient diagnosed with T-ALL developed LCH involving multiple systems during maintenance chemotherapy of T-AL. After treated with chemotherapy with improved result, the patient showed progression of the illness and refractory to the second-line treatment. We found c.G35A (p.G12D)mutation in the KRAS gene and used the targeted drug Trametinib for treatment. The treatment proved effective, leading to partial remission within a week. Three months after Trametinib treatment, the patient developed new lymphadenopathy. Biopsy revealed the existence of LCS. The disease progressed quickly, and the patient died 7 days after diagnosis of LCS. The case of patients with T-ALL then developing LCH and LCS sequentially is extraordinarily rare. The causes of the case is unclear and may be related to cell transdifferentiation, clonal evolution, and chemotherapy. Targeted drugs can contain this disease for a short time.

Deciphering the metabolites of multiple components in herbal medicine has far-reaching significance for revealing pharmacodynamic ingredients.However,most chemical components of herbal medicine are secondary metabolites with low content whose in vivo metabolites are close to trace amounts,making it difficult to achieve comprehensive detection and identification.In this paper,an efficient strategy was proposed:herb-derived metabolites were predicted according to the structural characteristics and metabolic reactions of chemical constituents in Corydalis Rhizoma and chemical structure screening tables for metabolites were conducted.The fragmentation patterns were summarized from represen-tative standards combining with specific cleavage behaviors to deduce structures of metabolites.Ion abundance plays an important role in compound identification,and high ion abundance can improve identification accuracy.The types of metabolites in different biological samples were very similar,but their ion abundance might be different.Therefore,for trace metabolites in biological samples,we used the following two methods to process:metabolites of high dose herbal extract were analyzed to char-acterize those of clinical dose herbal extracts in the same biological samples;cross-mapping of different biological samples was applied to identify trace metabolites based on the fact that a metabolite has different ion abundance in different biological samples.Compared with not using this strategy,44 more metabolites of clinical dose herbal extract were detected.This study improved the depth,breadth,and accuracy of current methods for herb-derived metabolites characterization.

Objective:To investigate the relationship between gene polymorphism of osteoprotegerin (OPG) and coal-burning endemic fluorosis in Guizhou Province.Methods:In 2018 and 2019, a case-control study was conducted in Bijie City, a typical coal-burning endemic fluorosis area in Guizhou Province, and 260 cases of coal-burning endemic fluorosis patients were selected as case group. According to the "Diagnostic Criteria for Endemic Skeletal Fluorosis" (WS 192-2008), the case group was divided into severe group (130 cases) and mild group (130 cases). At the same time, 130 cases without dental fluorosis and skeletal fluorosis symptoms were chosen as control group in Changshun County, a non-coal-burning endemic fluorosis area in Guizhou Province. Whole blood genomic DNA was extracted, and real-time fluorescence quantitative PCR with TaqMan-MGB probe was utilized to type the OPG gene rs2460985, rs2073618, rs6469804 and rs6993813 four single nucleotide polymorphism (SNP) loci of all samples, and genetic model analysis was performed to compare the frequency distribution of its alleles, genotypes and constructed haplotypes in control, mild and severe groups. Results:By Hardy-Weinberg equilibrium test, the genotype frequencies of the four SNP loci all reached genetic balance in control, mild and severe groups ( P > 0.05). There was a statistically significant difference in the genotype frequency of OPG gene rs6469804 locus among the three groups (χ 2 = 10.615, P < 0.05), and the difference in the genotype frequency of this locus between the control group and the severe group was statistically significant (χ 2 = 6.784, P < 0.05). The results of genetic model analysis showed that in comparison between the control group and the severe group, the optimal genetic model of rs6469804 locus was the overdominant genetic model, the frequency distribution of genotypes AA + GG and AG in the control group and the severe group was statistically significant [odds ratio ( OR) = 1.94, 95% confidence interval ( CI): 1.16 - 3.23, P < 0.05], genotype AG was a risk factor for coal-burning endemic fluorosis. In comparison between the control group and the mild group, the optimal genetic model of rs2073618 locus was the recessive genetic model, the frequency distribution of genotypes GG + GC and CC in the control group and the mild group was statistically significant ( OR = 3.17, 95% CI: 1.08 - 9.30, P < 0.05), genotype CC was a risk factor for coal-burning endemic fluorosis. In comparison between the control group and the mild group, haplotypes C-C-G-T and T-G-A-C were risk factors for coal-burning endemic fluorosis (adjusted OR = 2.41, 1.98, 95% CI: 1.29 - 4.50, 1.22 - 3.23, P < 0.05); in comparison between the control group and the severe group, haplotype T-G-A-C was a risk factor for coal-burning endemic fluorosis (adjusted OR = 1.87, 95% CI: 1.14 - 3.07, P < 0.05). Conclusion:OPG gene rs6469804 locus genotype AG and rs2073618 locus genotype CC may be risk factors for coal-burning endemic fluorosis.