Objective:To investigate the effect of tumor necrosis factor α (TNF-α) on the permeability of blood labyrinth barrier in C57BL/6J male mice and its possible mechanism.Methods:As for the design of animal experiment, twenty male C57BL/6J mice aged 6-8 weeks were randomly divided into control group and cisplatin group with 10 mice in each group by software method. The control group was intraperitoneally injected with normal saline every day, and the cisplatin group was intraperitoneally injected with 4 mg/kg cisplatin for 4 consecutive days. After administration, auditory brainstem response (ABR) was used to detect hearing changes in mice. HE staining was used to observe the morphological changes of mouse cochlea vasculature. The expression of TNF-α was detected by immunohistochemistry and ELISA. The permeability of the blood labyrinth barrier was observed by Evans blue staining. With respect to the design of cell experiment, primarily cultured cochlea pericytes (PC) and endothelial cells (EC) were divided into EC group, EC+TNF-α group, EC+PC group, EC+PC+TNF-α group, EC+PC+TNF-α+SB-3CT (MMP-9/MMP-2 secretion inhibitor) group, PC group, PC+TNF-α group, PC+TNF-α+LY294002 (PI3K/AKT pathway inhibitor) group, PC+LY294002 group. The protein expressions of ZO-1, VE-cadherin, MMP-9, MMP-2, PI3K, p-PI3K, AKT, and p-AKT were detected by Western blot. TEER and FITC-dextran penetration experiment were used to detect EC resistance and monolayer EC permeability, respectively. The data were statistically analyzed using GraphPad Prism 8 software.Results:In animal experiment, compared with control group, the ABR response threshold of mice in cisplatin group was increased ( P<0.01). The vaccine ular structure of the cochlea was disordered red, wrinkled and vacuole increased. The extravasation of vascular red fluorescent dye increased ( P<0.05), and also, levels of serum TNF-α and cochlear veins increased ( P<0.01). In cell experiment, by treatment of EC with different concentrations of cisplatin, 20 μmol cisplatin led to the highest expression of TNF-α ( P<0.01). The expression of TNF-α was the highest after 3 h intervention in EC ( P<0.05). Compared with those in EC+PC group, the resistance value of EC was decreased, the permeability of monolayers EC was increased, the expression of ZO 1 and VE cadherin proteins was decreased, and however, the resistance value was increased and the permeability of EC was decreased after the intervention of SB-3CT in EC+PC+TNF-α group. The expressions of ZO-1 and VE-cadherin proteins were increased ( P<0.05). The expression of MMP-9 increased after TNF-α intervention ( P<0.05), the expression of MMP-2 had no significant change, and the expression of p-PI3K/PI3K and p-AKT/AKT were increased ( P<0.05). The expression of MMP-9 decreased in PC+TNF-α+LY294002 group ( P<0.05). Conclusion:The hearing loss of C57BL/6J male mice induced by cisplatin may be related to the increased release of TNF-α from the blood labyrinth barrier EC in the cochlear stria vascularis, and the activation of PI3K/AKT signaling pathway by TNF-α in PC, which increases the secretion of MMP-9 from PC, ultimately leads to the increased permeability of the blood labyrinth barrier.

Objective:To investigate the effect of tumor necrosis factor α (TNF-α) on the permeability of blood labyrinth barrier in C57BL/6J male mice and its possible mechanism.Methods:As for the design of animal experiment, twenty male C57BL/6J mice aged 6-8 weeks were randomly divided into control group and cisplatin group with 10 mice in each group by software method. The control group was intraperitoneally injected with normal saline every day, and the cisplatin group was intraperitoneally injected with 4 mg/kg cisplatin for 4 consecutive days. After administration, auditory brainstem response (ABR) was used to detect hearing changes in mice. HE staining was used to observe the morphological changes of mouse cochlea vasculature. The expression of TNF-α was detected by immunohistochemistry and ELISA. The permeability of the blood labyrinth barrier was observed by Evans blue staining. With respect to the design of cell experiment, primarily cultured cochlea pericytes (PC) and endothelial cells (EC) were divided into EC group, EC+TNF-α group, EC+PC group, EC+PC+TNF-α group, EC+PC+TNF-α+SB-3CT (MMP-9/MMP-2 secretion inhibitor) group, PC group, PC+TNF-α group, PC+TNF-α+LY294002 (PI3K/AKT pathway inhibitor) group, PC+LY294002 group. The protein expressions of ZO-1, VE-cadherin, MMP-9, MMP-2, PI3K, p-PI3K, AKT, and p-AKT were detected by Western blot. TEER and FITC-dextran penetration experiment were used to detect EC resistance and monolayer EC permeability, respectively. The data were statistically analyzed using GraphPad Prism 8 software.Results:In animal experiment, compared with control group, the ABR response threshold of mice in cisplatin group was increased ( P<0.01). The vaccine ular structure of the cochlea was disordered red, wrinkled and vacuole increased. The extravasation of vascular red fluorescent dye increased ( P<0.05), and also, levels of serum TNF-α and cochlear veins increased ( P<0.01). In cell experiment, by treatment of EC with different concentrations of cisplatin, 20 μmol cisplatin led to the highest expression of TNF-α ( P<0.01). The expression of TNF-α was the highest after 3 h intervention in EC ( P<0.05). Compared with those in EC+PC group, the resistance value of EC was decreased, the permeability of monolayers EC was increased, the expression of ZO 1 and VE cadherin proteins was decreased, and however, the resistance value was increased and the permeability of EC was decreased after the intervention of SB-3CT in EC+PC+TNF-α group. The expressions of ZO-1 and VE-cadherin proteins were increased ( P<0.05). The expression of MMP-9 increased after TNF-α intervention ( P<0.05), the expression of MMP-2 had no significant change, and the expression of p-PI3K/PI3K and p-AKT/AKT were increased ( P<0.05). The expression of MMP-9 decreased in PC+TNF-α+LY294002 group ( P<0.05). Conclusion:The hearing loss of C57BL/6J male mice induced by cisplatin may be related to the increased release of TNF-α from the blood labyrinth barrier EC in the cochlear stria vascularis, and the activation of PI3K/AKT signaling pathway by TNF-α in PC, which increases the secretion of MMP-9 from PC, ultimately leads to the increased permeability of the blood labyrinth barrier.

OBJECTIVE: To explore the genetic basis for a rare case with Disorder of sex development. METHODS: Clinical data of the patient was collected. Chromosomal karyotyping, SRY gene testing, whole exome sequencing (WES), low-coverage massively parallel copy number variation sequencing (CNV-seq), fluorescence in situ hybridization (FISH), and whole genome sequencing (WGS) were carried out. RESULTS: The patient, a 14-year-old female, had manifested short stature and dysplasia of second sex characteristics. She was found to have a 46,XY karyotype and positive for the SRY gene. No pathogenic variant was found by WES, except a duplication at Yp11.32q12. The result of CNV-seq was 47,XYY. FISH has confirmed mosaicism for a dicentric Y chromosome. A 23.66 Mb duplication on Yp11.32q11.223 and a 5.16 Mb deletion on Yq11.223q11.23 were found by WGS. The breakpoint was mapped at chrY: 23656267. The patient's karyotype was ultimately determined as 46,X,psu idic(Y)(q11.223)/46,X,del(Y)(q11.223). CONCLUSION The combination of multiple methods has facilitated clarification of the genetic etiology in this patient, which has provided a reference for the clinical diagnosis and treatment.
Female ; Humans ; Adolescent ; DNA Copy Number Variations ; In Situ Hybridization, Fluorescence ; Y Chromosome ; Sexual Development ; Mosaicism

Objective:The purpose of this study was to investigate the characteristics of viral pathogen spectrum and the epidemiological characteristics of each viral pathogen in hospitalized cases associated with severe acute respiratory infection (SARI) in Luohe City, Henan Province from 2017 to 2019.Methods:Based the SARI Case Surveillance Platform, SARI cases were collected in Central Hospital of Luohe City, Henan Province from November 2017 to February 2019. In the end, 783 SARI cases were included, whose throat swabs were taken within 24 h of admission, as well as their demographic characteristics, onset time, clinical characteristics and other information recorded. At the same time, viral identification was performed, and the age and time distribution of each virus were analyzed.Results:The age of 783 SARI cases shown as M ( P 25, P 75) was 3 (1, 5) years old, ranging from 1 month to 95 years old. Children under 5 years old were the majority (71.01%). The males (61.81%) were more than females (38.18%). Among the 783 SARI cases, a total of 9 kind of viruses were identified with 64.88% (508/783) of the throat swabs tested positive for at least one virus. The positive rate of influenza virus and human respiratory syncytial virus were both 20.18% (158 cases), which was the highest among all the detected respiratory virus. The co-infection rate was 15.84% (124/783), among which double infection was the most common, accounting for 85.48% (106/124) of the co-infected cases. And human respiratory syncytial virus, human rhinovirus and influenza virus were the most common pathogen in co-infection cases. Moreover, the viral positive rate was 68.71% in children aged 5 years and 63.27% in people aged 60-95 years. Influenza and human respiratory syncytial virus dominated in winter and spring, while human parainfluenza virus was the main infection in summer. Conclusion:Influenza virus and human respiratory syncytial virus were the main viruses in throat swabs of SARI cases from 2017 to 2019 in Luohe City, Henan Province. There were differences in the age and seasonal epidemiological characteristics of each virus.

Objective:The purpose of this study was to investigate the characteristics of viral pathogen spectrum and the epidemiological characteristics of each viral pathogen in hospitalized cases associated with severe acute respiratory infection (SARI) in Luohe City, Henan Province from 2017 to 2019.Methods:Based the SARI Case Surveillance Platform, SARI cases were collected in Central Hospital of Luohe City, Henan Province from November 2017 to February 2019. In the end, 783 SARI cases were included, whose throat swabs were taken within 24 h of admission, as well as their demographic characteristics, onset time, clinical characteristics and other information recorded. At the same time, viral identification was performed, and the age and time distribution of each virus were analyzed.Results:The age of 783 SARI cases shown as M ( P 25, P 75) was 3 (1, 5) years old, ranging from 1 month to 95 years old. Children under 5 years old were the majority (71.01%). The males (61.81%) were more than females (38.18%). Among the 783 SARI cases, a total of 9 kind of viruses were identified with 64.88% (508/783) of the throat swabs tested positive for at least one virus. The positive rate of influenza virus and human respiratory syncytial virus were both 20.18% (158 cases), which was the highest among all the detected respiratory virus. The co-infection rate was 15.84% (124/783), among which double infection was the most common, accounting for 85.48% (106/124) of the co-infected cases. And human respiratory syncytial virus, human rhinovirus and influenza virus were the most common pathogen in co-infection cases. Moreover, the viral positive rate was 68.71% in children aged 5 years and 63.27% in people aged 60-95 years. Influenza and human respiratory syncytial virus dominated in winter and spring, while human parainfluenza virus was the main infection in summer. Conclusion:Influenza virus and human respiratory syncytial virus were the main viruses in throat swabs of SARI cases from 2017 to 2019 in Luohe City, Henan Province. There were differences in the age and seasonal epidemiological characteristics of each virus.

OBJECTIVE:To study the new formula of effective components in TCM for anti-allergic rhinitis (AR),and pro-vide reference for developing TCM preparations for anti-AR. METHODS:Using pseudoephedrine hydrochloride (0-13.5 mg/kg), total alkaloid extracts of Aconitum carmichaelii (0-21.18 mg/kg),volatile oil of asari radix (0-0.0092 mL/kg) in Mahuang Fuzi Xixin decoction as formula objects,uniform design method was used for drug grouping,and multiple regression analysis was con-ducted for the behavioral scores before and after administration,contents of histamine and immunoglobulin E (IgE) in serum of AR guinea pigs to obtain the best formula. Using Xinqin granule,Loratadine tablet,Mahuang Fuzi Xixin decoction respectively as positive control,efficacy of the best formula was verified from aspects of behavioral scores before and after administration,con-tents of histamine and IgE of AR guinea pigs. And the safety of the best formula was preliminarily observed through acute toxicity test in mice. RESULTS:The best formula was as follow as pseudoephedrine hydrochloride 11.25 mg/kg,total alkaloid extracts of A. carmichaelii 21.18 mg/kg,volatile oil of asari radix 0.0045 mL/kg. Compared with each positive drug group,there were no sig-nificant differences in behavioral scores before and after administration in the best formula group(P>0.05). While compared with Xinqin granule group and Mahuang Fuzi Xixin decoction group,histamine content in serum in the best formula group was signifi-cantly reduced (P<0.05);compared with Xinqin granule and Loratadine tablet group,IgE content in serum in the best formula group was significant decreased (P<0.05). Median lethal dose of the best formula was 1822.04 mg/kg. CONCLUSIONS:The screened best formula shows better effect than Xinqin granule and Mahuang Fuzi Xixin decoction in terms of reducing histamine content in serum,better than Loratadine tablet and Xinqin granule in terms of reducing IgE content in serum,with good safety, which indicates the feasibility of TCM effective component formula to a certain degree.

Objective To explore the changes of deceleration capacity of rate (DC) and analyze its correlation with heart rate variability (HRV) and other factors in patients with coronary heart disease. Methods One hundred and twenty-nine patients with coronary heart disease (coronary heart disease group) and 109 healthy people (control group) were enrolled in this study. DC and HRV parameters were measured by using digitized 24 h Holter. The correlation between DC and HRV parameters, other factors were analyzed. Results The levels of DC, SDNN, SDANN, SDNNi, PNN50, TP, LF, HF, AC in coronary heart disease group were significantly lower than those in control group:(5.64±1.67) ms vs. (6.71±1.47) ms, (106.60±20.53) ms vs. (138.82±31.22) ms, (96.94±20.06) ms vs. (127.47±31.87) ms,(28.53±14.75) ms vs. (52.24±14.65) ms, 87.72%vs. 103.86%,(1 967.10±966.16) ms2/Hz vs. (2 846.70±1 443.41) ms2/Hz,(326.43±195.35) ms2/Hz vs.(457.64±254.30) ms2/Hz, 85.88 vs. 106.39, (-6.18±2.15) ms vs. (-7.00±2.51) ms, P<0.05 or<0.01. DC was correlated with SDNNi, PNN50,TP,LF, HF, AC both in total population or in coronary heart disease group and control group by using multiple linear correlation analysis ( r=0.586, 0.356, 0.531, 0.563, 0.435,-0.433, P<0.01). After removing confounders, DC was correlated with age, SDNNi, rMSSD, PNN50 and AC (P<0.01). Conclusions DC decreases in patients with coronary heart disease and is strong correlativity with HRV parameters. DC could be used for quantitative detection of autonomic nervous function.

Objective To compare the clinical effect of arthroscopic single-row and suture-bridge double-row fixation of full-thickness rotator cuff tear.Methods A retrospective study was conducted on 40 patients with full-thickness rotator cuff tear treated by single-row and suture-bridge double-row fixation between May 2010 and May 2012.Single-row rotator cuff repair was performed in 18 patients and doublerow repair in 22 patients.The two techniques were compared in aspects of complications,recovery time to daily life,time to achieve satisfaction score,re-tear rate,pre-and post-operative VAS,University of California at Los Angeles Shoulder Scores (UCLA),and American Shoulder and Elbow Surgeons (ASES).Results Mean period of follow-up was 15.6 months (range,13-24 months).Both treatment were effective in improving VAS,UCLA,and ASES,but the differences were insignificant (P ＞ 0.05).Recovery time to daily life,time to achieve satisfaction score,and large rotator cuff re-tear rate were 69.2 ± 16.6)d,(196.4 ±24.6)d,and 4/5 respectively in single-row fixation,with significant differences from (54.1 ± 13.3)d,(165.0 ±20.6)d,and 1/8 in suture-bridge double-row fixation (P ＜0.05).Conclusion Both treatments are effective for rotator cuff reconstruction,but suture-bridge double-row fixation provides earlier recovery to daily life,shorter time to achieve satisfaction score,and lower incidence of large rotator cuff retear.

Objective To explore the correlation between cystatin C (Cys C) and intima-media thickness of carotid artery (CIMT) in patients with hypertension.Methods One hundred and one patients with hypertension (hypertension group) and 54 healthy people (control group) were enrolled in this study.The level of serum Cys C was measured and CIMT was detected by B ultrasound.The correlation between Cys C and CIMT was analyzed.Results The level of Cys C and CIMT in hypertension group were significantly higher than those in control group [(0.92 ±0.21) mg/L vs.(0.85 ±0.20) mg/L,(0.91 ±0.16) mm vs.(0.65 ± 0.15) mm] (P ＜ 0.05 or ＜ 0.01).Multiple linear correlation analysis showed that Cys C and CIMT was positively correlated in total population or hypertension group or control group (r =0.412,0.443,0.315,P ＜0.01).Conclusion Serum Cys C is associated with the degree of hypertension arteriosclerosis,and Cys C may be involved in atherosclerosis.

OBJECTIVETo investigate the protective effect of dexmedetomidine (Dex) preconditioning against ischemia/reperfusion (I/R) injuries in isolated rat hearts and its relation to mitochondrial permeability transition pore (mPTP) and mitochondrial ATP-sensitive K(+) channel (mitoKATP).

METHODSThe hearts of male SD rats were isolated to mount on the Langendorff apparatus and subjected to 30 min global ischemia followed by 120 min reperfusion. The isolated hearts were treated with Dex (10 nmol/L) before ischemia for 15 min. The left ventricular hemodynamic parameters,coronary flow (CF) and the lactate dehydrogenase (LDH) release in the coronary effluent at 5 min reperfusion were measured. The formazan content was assayed to determine the myocardial viability at the end of reperfusion.

RESULTSCompared with normal controls, I/R markedly decreased the left ventricular developed pressure and CF during the whole reperfusion period and the formazan content; while the left ventricular end diastolic pressure and LDH release were significantly increased. Dex preconditioning markedly improved the myocardial viability and cardiac function (P<0.01), which were reversed by the treatment with both atractyloside (20 μmol/L before ischemia), an opener of mPTP, and 5-hydroxydecanoate (100 μmol/L at the beginning of reperfusion), an inhibitor of mitoKATP, for 20 min.

CONCLUSIONDex has protective effect against I/R injuries in isolated rat hearts, which may be related to inhibiting the opening of mPTP at the beginning of reperfusion and activating mitoKATP before ischemia.

Animals ; Dexmedetomidine ; pharmacology ; In Vitro Techniques ; Ischemic Preconditioning, Myocardial ; Male ; Mitochondrial Membrane Transport Proteins ; drug effects ; Myocardial Reperfusion Injury ; physiopathology ; prevention & control ; Potassium Channels ; drug effects ; Rats ; Rats, Sprague-Dawley