Sensorineural hearing loss is one of the most common sensory disorders. In recent years, auditory neuropathy spectrum disorders caused by mutations in the OTOF gene have garnered significant attention worldwide, marking it as the first deafness gene with breakthroughs in gene therapy. Most patients with OTOF gene mutations present with stable, congenital, or prelingual onset of hearing loss, which can range from severe to profound and even complete hearing loss. However, a minority of patients may exhibit mild to moderate progressive hearing loss or temperature-sensitive hearing loss. This review further explores the genotype-phenotype relationship of the OTOF gene based on reported cases in China and abroad. Additionally, we analyze the characteristics of the natural history of OTOF gene mutations within the Chinese population. This study aims to provide a reference for the clinical diagnosis, evaluation, and treatment of hearing loss associated with OTOF gene mutations.
Humans ; Mutation ; Phenotype ; Genotype ; Hearing Loss, Sensorineural/genetics* ; Membrane Proteins/genetics*

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal disease, and has become a major global health issue. Individuals with IBD face an elevated risk of developing colorectal cancer (CRC), and recent studies have indicated that mitochondrial dysfunction plays a pivotal role in the pathogenesis of both IBD and CRC. This review covers the pathogenesis of IBD and CRC, focusing on mitochondrial dysfunction, and explores pharmacological targets and strategies for addressing both conditions by modulating mitochondrial function. Additionally, recent advancements in the pharmacological modulation of mitochondrial dysfunction for treating IBD and CRC, encompassing mitochondrial damage, release of mitochondrial DNA (mtDNA), and impairment of mitophagy, are thoroughly summarized. The review also provides a systematic overview of natural compounds (such as flavonoids, alkaloids, and diterpenoids), Chinese medicines, and intestinal microbiota, which can alleviate IBD and attenuate the progression of CRC by modulating mitochondrial function. In the future, it will be imperative to develop more practical methodologies for real-time monitoring and accurate detection of mitochondrial function, which will greatly aid scientists in identifying more effective agents for treating IBD and CRC through modulation of mitochondrial function.

Objective To observe the effect of Xinmailong injection on microcirculation in patients with septic shock,so as to understand the application effect and value of Xinmailong injection in patients with septic shock.Methods A total of 82 patients with septic shock treated in the intensive care unit of our hospital were selected as the research objects and randomly divided into two groups.41 patients in the control group were treated with conventional septic shock cluster therapy,and 41 patients in the treatment group were treated with Xinmailong injection on the basis of cluster therapy in the control group.Then hemodynamic parameters(HR,CVP,CO,MAP,SVR),hemorheology(whole blood reducing viscosity,hematocrit,fibrinogen,platelet aggregation rate),microcirculation perfusion indexes(oxygenation index,blood lactate level,SCVO2,Pcv-aCO2)and 28-day survival rate were detected and compared between the two groups before and after treatment.Results Before treatment,there were no significant differences in hemodynamic parameters,blood rheology and microcirculation perfusion indexes between the two groups(P>0.05).After treatment,the above test results of the two groups were signifi-cantly improved,and the test results of the treatment group were significantly better than those of the control group,and the 28-day survival rate was also better than that of the control group.The differences were statistically significant(P<0.05).Conclusion Xinmailong injection can significantly improve the hemodynamic parameters,blood rheology and microcirculation perfusion indexes,and improve the 28-day survival rate of patients with sepsis.It has a positive clinical effect in the treatment of septic shock patients.

ObjectiveTo observe the efficacy and safety of Tongguan Capsule（通冠胶囊）on ventricular remodeling in patients after acute myocardial infarction （AMI）， and to explore the possible mechanism. MethodsA total of 53 ST-segment elevation myocardial infarction （STEMI） patients were collected and randomly divided into 26 cases in the treatment group and 27 cases in the control group. The control group was given conventional therapy after percutaneous coronary intervention （PCI） for AMI， and the treatment group was given Tongguan Capsules （4.5 g each time， 3 times a day） on the basis of the control group. The course of treatment was 12 weeks. Echocardiographic data and stool samples were collected from subjects before and after the intervention， and left ventricular ejection fraction （LVEF）， left ventricular end-diastolic volume index （LVEDVi）， left ventricular end-systolic volume index （LVESVi）， left ventricular mass index （LVMi） were measured and calculated， so as to compare the number of cases of left ventricular remodeling in the two groups. At the same time， 16S rDNA sequencing was performed on the stool samples to analyze the diversity of gut microbiota （GM）， the composition of the GM， the GM difference between the groups； recording the incidence of major adverse cardiovascular events （MACEs） and adverse reactions of patients in the two groups during the study period； and performing Spearman's correlation analyses of the post-treatment flora data with LVEF， LVEDVi， LVESVi， LVM， and LVMi in the two groups. ResultsOne case fail to follow up in the treatment group and 2 cases fail to follow up in the control group， and 25 cases in each of the two groups were finally included in the analysis. LVEDVi， LVESVi， and LVMi of the control group after treatment were higher than those before treatment （P＜0.05）； after treatment， LVEDVi， LVESVi and LVMi in the treatment group were lower than those in the control group （P＜0.05）. Left ventricular remodeling occurred in 5 cases （20.00%） in the treatment group and 13 cases （52.00%） in the control group， and the incidence of left ventricular remodeling in the treatment group was lower than that in the control group （P=0.03）. After treatment， the ACE estimation and Chao estimation of bacterial abundance in the treatment group were higher than that before treatment and that in the control group （P＜0.05）. The treatment group showed an increase in Mycobacterium anisopliae phylum and a decrease in Mycobacterium thickum， Mycobacterium anisopliae phylum， and Mycobacterium patella phylum after treatment （P＜0.05）. When comparing between groups after treatment， the relative abundance of Prevotella， Agathobacter， Dialister， Eubacterium coprostanoligenes group was up-reuglated and the relative abundance of Enterococcus was down-regulated in the treatment group（P＜0.05 or P＜0.01）. There was no statistically significant difference in the incidence of MACEs and the occurrence of adverse reactions between groups during treatment （P＞0.05）. The results of correlation analysis showed that Prevotella were positively correlated with LVEF and negatively correlated with LVEDVi， LVESVi， LVM， and LVMi （P＜0.01）. Agathobacter group were negatively correlated with LVEDVi， LVESVi （P＜0.01）； Enterococcus group were positively correlated with LVESVi （P＜0.05）. ConclusionTongguan Capsules can improve ventricular remodeling in patients with acute ST-segment elevation myocardial infarction with better safety； its mechanism may be related to adjusting the enrichment of related bacteria such as Prevotella， Dialister and Enterococcus and other related bacterial genera， increasing the colonization and diversity of beneficial bacteria， and adjusting the structure of GM.

Objective To observe hemodynamic characteristics and the correlation with syndrome types of traditional Chinese medicine (TCM) in patients with septic shock, so as to direct the treatment based on syndrome differentiation. Methods A prospective observation was conducted. Sixty-eight patients with septic shock admitted to the Department of Critical Care Medicine of Dade Road General Hospital of Guangdong Hospital of TCM from January 2013 to July 2015 were enrolled. Pulse indicating continuous cardiac output (PiCCO) was used to monitor the hemodynamic changes, including heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), cardiac index (CI), global end diastolic volume index (GEDVI), extravascular lung water index (EVLWI), maximum rate of the increase in pressure (dPmax) and systemic vascular resistance index (SVRI), for assessment of hemodynamics. According to the CI, the patients were divided into two groups , i.e. high CI group (CI ≥ 50.0 mL·s-1·m-2, n = 34) and low CI group (CI < 50.0 mL·s-1·m-2, n = 34), and the clinical and hemodynamic characteristics of two groups were investigated. The TCM differentiation was conducted with four syndromes and four methods, and the hemodynamic characteristics of different syndrome types were investigated, the correlation between the TCM syndrome factors and hemodynamic parameters was analyzed. The patients were divided into survival group and death group, and clinical parameters and hemodynamic characteristics were compared between two groups. Results The acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score and blood glucose of low CI group were higher than those of high CI group [APACHEⅡ score: 24.4±7.2 vs. 19.8±7.4, t = -2.279, P = 0.023; blood glucose (mmol/L): 9.7 (7.7, 14.6) vs. 6.7 (5.6, 10.0), Z = -2.257, P = 0.024], CI and GEDVI were lowered [CI (mL·s-1·m-2): 36.7±8.3 vs. 68.4±16.7, t = 10.285, P = 0.000; GEDVI (mL/m2): 689.0 (566.0, 883.8) vs. 838.5 (692.8, 1 247.3), Z = -2.711, P = 0.007], while SVRI was increased [kPa·s·L-1·m-2: 248.7 (202.1, 324.5) vs. 143.4 (102.7, 171.4), Z = -5.336, P = 0.000]. Accompanied symptoms were found to occur more commonly in septic shock patients, and the most common syndrome elements were Qi deficiency syndrome (n = 45), blood stasis syndrome (n = 40), heat-toxin syndrome (n = 37), Fushi syndrome (n = 24) and Yin deficiency syndrome (n = 10), respectively. There was no significant difference in hemodynamic parameters among patients with five types of syndrome (all P > 0.05). However, only the CI of those with Qi deficiency syndrome was significantly lower than that of heat-toxin syndrome (mL·s-1·m-2: 48.3±18.3 vs. 53.3±21.7, P < 0.05). While the results after removing the effect of accompanied symptoms showed that CI of Qi deficiency syndrome was significantly lower than that of non-Qi deficiency syndrome (mL·s-1·m-2: 48.3±18.3 vs. 61.7±21.7, t = -2.783, P = 0.007), CI of heat-toxin syndrome was significantly higher than that of non-heat-toxin syndrome (mL·s-1·m-2: 58.3±21.7 vs. 48.3±16.7, t = 2.133, P = 0.037), EVLWI of blood stasis syndrome was significantly lower than that of non-blood stasis syndrome [mL/kg: 10.0 (7.0, 15.1) vs. 14.9 (8.5, 26.8), Z = -2.075, P = 0.038]. Compared with survival group (n = 38), APACHEⅡ score in death group (n = 30) was increased (25.8±8.4 vs. 19.1±5.4, t = -3.940, P = 0.000), the proportion of continuous renal replacement therapy (CRRT) was increased [60.0% (18/30) vs. 31.6% (12/38), χ2 = 5.493, P = 0.019], HR was increased (bpm: 118.5±20.5 vs. 98.1±19.9, t = -4.157, P = 0.000), and the proportion of Qi deficiency syndrome was increased [86.7% (26/30) vs. 50.0% (19/38), χ2 = 10.070, P = 0.002]. Conclusions Patients with sepsis shock may be divided into high-output and low-resistance & low-output and high-resistance groups according to hemodynamics, with respective hemodynamic characteristics. Hemodynamic performance differed among different syndrome types, and there was a certain relationship. Hemodynamic monitoring with PiCCO was a useful supplement of TCM, which was good for the evidence-based medicine.

ObjectiveTo investigate the effects of Xuebijing injection on hemodynamics, cardiac function, and endothelial function in patients with severe sepsis in order to study the therapeutic effect of Xuebijing in the treatment of severe sepsis.Methods A prospective randomized controlled trial was conducted. Sixty-six severe sepsis patients admitted to the Department of Critical Care Medicine of Guangdong Hospital of Traditional Chinese Medicine from March 2013 to February 2014 were enrolled. The patients were divided into control group (n = 31) and Xuebijing group (n= 35). The patients in both groups were treated according to 2012 international guidelines for management of severe sepsis and septic shock, and the patients in Xuebijing group received Xuebijing injection of 50 mL (added with 100 mL of 0.9% sodium chloride injection) twice a day for 5 days, and those in control group received instead 150 mL of 0.9% sodium chloride injection for 5 days. The heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), and dosage of vasoactive drugs before and 1 day and 5 days after treatment were determined for hemodynamics assessment. Blood lactic acid (Lac), central venous oxygen saturation (ScvO2), and difference in arterial-venous blood carbon dioxide pressure (Pv-aCO2) were determined for microcirculation assessment. The left ventricular ejection fraction (LVEF), cardiac output (CO), left ventricular end diastolic diameter (LVEDD), the ratio of blood flow of mitral orifice between rapid filling period and atrial systole period (E/A), and B-type natriuretic peptide (BNP) were determined for cardiac function assessment. Vascular endothelial growth factor (VEGF) and soluble receptor (sFLT-1) were assessed for endothelial function assessment. The relationship among the indexes of the hemodynamics, microcirculation, cardiac function, and endothelial function was analyzed with Pearson related-analysis.Results After treatment, HR, MAP, CVP, Lac, ScvO2, and Pv-aCO2 were improved in both groups compared with those before treatment, and the dosage of norepinephrine (NE) was decreased in Xuebijing group. Compared with control group, MAP at 5 days after treatment in Xuebijing group was significantly increased [mmHg (1 mmHg =0.133 kPa): 74.9±10.7 vs. 70.2±6.6,P< 0.05], the dosage of NE was decreased [μg·kg-1·min-1: 0.01 (0.00, 0.22) vs. 0.10 (0.05, 0.80),P< 0.05], LVEF was significantly increased (0.617±0.125 vs. 0.533±0.129,P< 0.05), BNP was significantly decreased [ng/L: 117.3 (52.0, 443.0) vs. 277.2 (67.9, 2 370.2),P< 0.05], while VEGF showed no significant change (ng/L: 101.1±23.2 vs. 89.6±20.5,P> 0.05), and sFLT-1 was significantly decreased (ng/L:245.7±86.2 vs. 295.1±95.1,P< 0.05). It was shown by Pearson coefficient bivariate correlation analysis that sFLT-1 was negatively correlated with MAP and ScvO2 (r= -0.569,P= 0.000;r= -0.341,P= 0.008) 5 days after treatment, while it was positively associated with Lac and acute physiology and chronic health evaluationⅡ (APACHEⅡ) score (r= 0.749,P= 0.000;r= 0.645,P= 0.000).Conclusions In patients with severe sepsis, there are hemodynamics disorders and effect in microcirculation perfusion. Xuebijing injection can improve hemodynamics and cardiac function in the patients with severe sepsis, and the mechanism may be related to the improvement of endothelial function.

[ ABSTRACT] AIM:To develop the cell model of polymer/liquid crystal and to study the effect of their elasticity on the adhesion of rat bone marrow mesenchymal stem cells (rBM-MSCs).METHODS: Using the method of solvent e-vaporation induced phase separation, the cell model of polymer/liquid crystal was constructed.The surface morphology and phase separation structure were determined by polarized optical microscopy ( POM) , scanning electron microscopy ( SEM) and small angle X-ray scattering ( SAXS ) .rBM-MSCs were separated and expanded by adherent culture.The surface markers of rBM-MSCs were detected by flow cytometry.The cells were induced to osteogenic differentiation and adipogenic differentiation for 2 weeks.After 3 passages, the cells were divided into 4 groups, including total PU control group, 10%membrane group, 30%membrane group and 50%membrane group.The cells were then incubated with rhodamine phalloi-din for cytoskeleton staining and were observed under the confocal laser scanning microscope after cultured for 24 h.RE-SULTS:The cell model of polymer/liquid crystal was constructed successfully using the method of solvent evaporation in-duced phase separation.Flow cytometry results showed that the rBM-MSCs positively expressed CD29, CD44 and CD90, and negatively expressed CD34 and CD45.After stained with alizarin red S and oil red O, the calcium nodule and lipid droplets in rBM-MSCs were observed obviously.The cytoskeleton staining result indicated that the area in total PU control group, 10%membrane group and 30%membrane group were greater, and the actin microfilaments were also clearer than
that in 50%membrane group.CONCLUSION:The cell model with suitable content of liquid crystal made a contribution to the rBM-MSCs’ adhesion, but too much liquid crystal inhibits cell adhesion.

Objective To investigate the serum level of carboxy-terminal telopeptide of type I collagen (ICTP) and explore its correlation with MMP-2 and MMP-9 in patients with coronary artery disease (CHD). Methods A total of 103 CHD patients treated in our hospital between October, 2013 and May, 2014 were enrolled, including 39 with stable angina pectoris (SAP), 39 with unstable angina (UA), and 25 with acute myocardial infarction (AMI), with 38 non-CHD volunteers as the control group. The serum levels of ICTP, MMP-2, and MMP-9 were detected in all the subjects using enzyme-linked immunosorbent assay (ELISA). Results No significant difference in serum levels of MMP-2, MMP-9, or ICTP was found between the control and SAP groups or between UA and AMI groups (P>0.05), but the latter two groups had significantly higher serum levels of MMP-2, MMP-9, and ICTP than the former two groups (P<0.05). Serum ICTP level was found to negatively correlated with the fibrotic area and positively with the lipid component in the plaques (P<0.05). Regression analysis revealed significant positive correlations of serum ICTP with MMP-2 and MMP-9 (P<0.05). Conclusions An elevated serum ICTP level is indicative of the presence of unstable plaques in CHD patients. Serum ICTP is more strongly correlated with MMP-2 than with MMP-9, and can be used as a non-invasive marker for assessing vulnerable plaques in patients with acute coronary syndrome.

Objective To investigate the serum level of carboxy-terminal telopeptide of type I collagen (ICTP) and explore its correlation with MMP-2 and MMP-9 in patients with coronary artery disease (CHD). Methods A total of 103 CHD patients treated in our hospital between October, 2013 and May, 2014 were enrolled, including 39 with stable angina pectoris (SAP), 39 with unstable angina (UA), and 25 with acute myocardial infarction (AMI), with 38 non-CHD volunteers as the control group. The serum levels of ICTP, MMP-2, and MMP-9 were detected in all the subjects using enzyme-linked immunosorbent assay (ELISA). Results No significant difference in serum levels of MMP-2, MMP-9, or ICTP was found between the control and SAP groups or between UA and AMI groups (P>0.05), but the latter two groups had significantly higher serum levels of MMP-2, MMP-9, and ICTP than the former two groups (P<0.05). Serum ICTP level was found to negatively correlated with the fibrotic area and positively with the lipid component in the plaques (P<0.05). Regression analysis revealed significant positive correlations of serum ICTP with MMP-2 and MMP-9 (P<0.05). Conclusions An elevated serum ICTP level is indicative of the presence of unstable plaques in CHD patients. Serum ICTP is more strongly correlated with MMP-2 than with MMP-9, and can be used as a non-invasive marker for assessing vulnerable plaques in patients with acute coronary syndrome.

ObjectiveTo evaluate the clinical efficacy and safety of astragalus injection on the immune function in patients with senile sepsis.Methods Sixty patients with old age sepsis in Critical Care Medicine Department of Guangdong Provincial Traditional Chinese Medicine Hospital were enrolled and randomly assigned into control and treatment groups according to the table of random numbers, 30 cases in each group. According to 2012 sepsis guidelines for treatment, including antibacterial drug, mechanical ventilation, visceral function support, etc., the therapy was given to the control group; besides the treatment in the control group, intravenous drip of 60 mL astragalus injection(10 mL per ampoule) in 250 mL 0.9% normal saline was additionally given in the treatment group, once a day for 7 days. Before and after treatment, the immunological indexes, acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, sequential organ failure assessment(SOFA) score, duration of mechanical ventilation and time of stay in intensive care unit(ICU), 28-day mortality and adverse drug reactions were compared between the two groups.Results Before treatment, there were no statistically significant differences in CD3+, CD3+CD4+, CD3+CD8+ and T helper cells /T suppressor cells(Th/Ts)levels between the two groups(allP>0.05), while CD3-NK+ of the control group was significantly higher than that in the treatment group〔(10.47±6.22)% vs. (6.26±4.13)%,P<0.05〕. After treatment in treatment group, CD3+, CD3+CD4+ and CD3-NK+ were increased, CD3+CD8+,Th/Ts were decreased compared with those before treatment; in the control group after treatment, CD3+,CD3+CD8+ and CD3-NK+ were decreased and CD3+CD4+ and Th/Ts increased compared with those before treatment. In the comparisons between the treatment group and control group after treatment, the differences in CD3+, CD3+CD4+ and CD3+CD8+ had statistical significance〔CD3+:(30.30±17.17)% vs.(41.91±22.29)%, CD3+CD4+:(31.54±13.24)% vs.(40.08±15.28)%, CD3+CD8+:(14.25±8.10)% vs.(9.52±9.33)%,allP<0.05〕; while the differences in Th/Ts and CD3-NK+ had no statistical significance(bothP>0.05). After treatment in the treatment group, IgG was increased compared with that in the control group〔IgG(g/L): 13.07±5.43 vs. 10.10±3.96,P<
0.05〕. The differences in IgA, IgM, complement(C3,C4) and total serum complement activity(CH50) in the comparisons between the two groups had no statistical significance after treatment(allP>0.05). The differences in APACHEⅡ score(13.83±6.18 vs. 15.90±7.48), SOFA score(7.38±4.66 vs. 6.89±4.19), time of stay in ICU(day: 11.63±5.13 vs. 13.62±8.08), invasive ventilation time(hour: 155.44±119.68 vs. 224.08±174.15) and noninvasive ventilation time(hour: 55.55±42.24 vs. 98.57±43.17) had no statistical significance in comparisons between the treatment group and control group after treatment(allP>0.05). The difference in 28-day mortality had no statistical significance in comparison between the treatment group and control group〔16.7%(5/30) vs. 20.0%(6/30),P>0.05〕. In 60 cases, there were 2 patients with adverse drug reaction, one diarrhea and another little rashes, the rest of the patients did not appear any drug side effect.ConclusionAstragalus injection combined with conventional western medicine therapy possibly has certain effect on adjustment of disturbance of immunologic functions in old patients with sepsis, and its therapeutic safety is well.