Clinical Characteristics, Diagnosis, and Therapeutics of COVID-19: A Review.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that suddenly emerged at the end of December 2019 and caused coronavirus disease 2019 (COVID-19) continues to afflict humanity, not only seriously affecting healthcare systems but also leading to global social and economic imbalances. As of August 2022, there were approximately 580 million confirmed cases of COVID-19 and approximately 6.4 million confirmed deaths due to this disease. The data are sufficient to highlight the seriousness of SARS-CoV-2 infection. Although most patients with COVID-19 present primarily with respiratory symptoms, an increasing number of extrapulmonary systemic symptoms and manifestations have been associated with COVID-19. Since the outbreak of COVID-19, much has been learned about the disease and its causative agent. Therefore, great effort has been aimed at developing treatments and drug interventions to treat and reduce the incidence of COVID-19. In this narrative review, we provide a brief overview of the epidemiology, mechanisms, clinical manifestations, diagnosis, and therapeutics of COVID-19.

Differential diagnosis of lymphoma with 18F-FDG PET/CT in patients with fever of unknown origin accompanied by lymphadenopathy.

PURPOSE: To investigate the value of 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the differential diagnosis of lymphoma in patients with fever of unknown origin (FUO) accompanied by lymphadenopathy and to develop a simple scoring system to distinguish lymphoma from other etiologies. METHODS: A prospective study was conducted on patients with classic FUO accompanied by lymphadenopathy. After standard diagnostic procedures, including PET/CT scan and lymph-node biopsy, 163 patients were enrolled and divided into lymphoma and benign groups according to the etiology. The diagnostic utility of PET/CT imaging was evaluated, and beneficial parameters that could improve diagnostic effectiveness were identified. RESULTS: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PET/CT in diagnosing lymphoma in patients with FUO accompanied by lymphadenopathy were 81.0, 47.6, 59.3, and 72.7%, respectively. The lymphoma prediction model combining high SUVmax of the "hottest" lesion, high SUVmax of the retroperitoneal lymph nodes, old age, low platelet count, and low ESR had an area under the curve of 0.93 (0.89-0.97), a sensitivity of 84.8%, a specificity of 92.9%, a PPV of 91.8%, and an NPV of 86.7%. There was a lower probability of lymphoma for patients with a score < 4 points. CONCLUSIONS: PET/CT scans show moderate sensitivity and low specificity in diagnosing lymphoma in patients with FUO accompanied by lymphadenopathy. The scoring system based on PET/CT and clinical parameters performs well in differentiating lymphoma and benign causes and can be used as a reliable noninvasive tool. REGISTRATION NUMBER: This study on FUO was registered on http://www. CLINICALTRIALS: gov on January 14, 2014, with registration number NCT02035670.

Infection-associated Hemophagocytic Syndrome in Critically Ill Patients with COVID-19.

Infection-associated hemophagocytic syndrome (IAHS), a severe complication of various infections, is potentially fatal. This study aims to determine whether IAHS occurs in critically ill patients with coronavirus disease 2019 (COVID-19). We conducted a retrospective observational study on 268 critically ill patients with COVID-19 between February 1st, 2020 and February 26th, 2020. Demographics, clinical characteristics, laboratory results, information on concurrent treatments and outcomes were collected. A diagnosis of secondary hemophagocytic lymphohistiocytosis (sHLH) was made when the patients had an HScore greater than 169. Histopathological examinations were performed to confirm the presence of hemophagocytosis. Of 268 critically ill patients with confirmed SARS-CoV-2 infection, 17 (6.3%) patients had an HScore greater than 169. All the 17 patients with sHLH died. The interval from the onset of symptom of COVID-19 to the time of a diagnosis of sHLH made was 19 days and the interval from the diagnosis of sHLH to death was 4 days. Ten (59%) patients were infected with only SARS-CoV-2. Hemophagocytosis in the spleen and the liver, as well as lymphocyte infiltration in the liver on histopathological examinations, was found in 3 sHLH autopsy patients. Mortality in sHLH patients with COVID-19 is high. And SARS-CoV-2 is a potential trigger for sHLH. Prompt recognition of IAHS in critically ill patients with COVID-19 could be beneficial for improving clinical outcomes.

Synthesis, characterization and preliminary biological evaluation of chrysin amino acid derivatives that induce apoptosis and EGFR downregulation.

Chrysin amino acid derivatives were synthesized to evaluate for their antiproliferative activities. Among them, N-(7-((5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl)oxy)valeryl)-L-leucine (8c) displayed the most remarkable inhibitory activities against MCF-7 cells with IC50 values of 16.6 µM. Preliminary mechanistic studies showed that 8c could inhibit the colony formation and migration of MCF-7 cells. Flow cytometry analysis demonstrated that 8c mediated cell apoptosis and the prolongation of cell cycle progression in G1/S-phase against MCF-7 cells. Besides, 8c displayed the moderate inhibition against EGFR. Western blot assay suggested that 8c significantly inhibited EGFR phosphorylation. Molecular docking showed that 8c can bind the EGFR kinase well.

CAPRL Scoring System for Prediction of 30-day Mortality in 949 Patients with Coronavirus Disease 2019 in Wuhan, China: A Retrospective, Observational Study.

Background: Coronavirus disease 2019 (COVID-19) is a serious and even lethal respiratory illness. The mortality of critically ill patients with COVID-19, especially short term mortality, is considerable. It is crucial and urgent to develop risk models that can predict the mortality risks of patients with COVID-19 at an early stage, which is helpful to guide clinicians in making appropriate decisions and optimizing the allocation of hospital resoureces. Methods: In this retrospective observational study, we enrolled 949 adult patients with laboratory-confirmed COVID-19 admitted to Tongji Hospital in Wuhan between January 28 and February 12, 2020. Demographic, clinical and laboratory data were collected and analyzed. A multivariable Cox proportional hazard regression analysis was performed to calculate hazard ratios and 95% confidence interval for assessing the risk factors for 30-day mortality. Results: The 30-day mortality was 11.8% (112 of 949 patients). Forty-nine point nine percent (474) patients had one or more comorbidities, with hypertension being the most common (359 [37.8%] patients), followed by diabetes (169 [17.8%] patients) and coronary heart disease (89 [9.4%] patients). Age above 50 years, respiratory rate above 30 beats per minute, white blood cell count of more than10 × 109/L, neutrophil count of more than 7 × 109/L, lymphocyte count of less than 0.8 × 109/L, platelet count of less than 100 × 109/L, lactate dehydrogenase of more than 400 U/L and high-sensitivity C-reactive protein of more than 50 mg/L were independent risk factors associated with 30-day mortality in patients with COVID-19. A predictive CAPRL score was proposed integrating independent risk factors. The 30-day mortality were 0% (0 of 156), 1.8% (8 of 434), 12.9% (26 of 201), 43.0% (55 of 128), and 76.7% (23 of 30) for patients with 0, 1, 2, 3, ≥4 points, respectively. Conclusions: We designed an easy-to-use clinically predictive tool for assessing 30-day mortality risk of COVID-19. It can accurately stratify hospitalized patients with COVID-19 into relevant risk categories and could provide guidance to make further clinical decisions.

Combined clinical parameters improve the diagnostic efficacy of 18F-FDG PET/CT in patients with fever of unknown origin (FUO) and inflammation of unknown origin (IUO): A prospective study in China.

OBJECTIVES: To improve the diagnostic efficacy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for Chinese patients with fever of unknown origin (FUO) and inflammation of unknown origin (IUO), with combined clinical parameters. MATERIALS AND METHODS: FUO/IUO patients who underwent a standard diagnostic work-up and 18F-FDG PET/CT scanning were enrolled and divided into a local uptake lesion subgroup and a non-specific abnormal uptake subgroup. Beneficial clinical parameters for improving the diagnostic efficacy of PET/CT were identified. RESULTS: From January 2014 to January 2019, 253 FUO/IUO patients were studied. In total, 147 patients had local uptake lesions and 106 patients had non-specific abnormal uptake. In the local uptake lesion group, the positioning accuracy of PET/CT was 37.2% in grades 1 and 2, and 66.3% in grades 3 and 4. With the following combination of clinical parameters, the positioning accuracy increased to 75.0% and 90.0%, respectively: time from admission to performing PET/CT scanning <6.5 days and C-reactive protein level >95 mg/l. In the non-specific abnormal uptake group, the combination of sex (male), bicytopenia, and lactic dehydrogenase improved the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for diagnosing malignancy from 64.3%, 69%, 60%, and 72.7%, respectively, to 83.3%, 81%, 81.4%, and 82.9%, respectively. With the combination of sex (male), white blood count, serum ferritin level, and hepatosplenomegaly, the infection prediction model had a sensitivity, specificity, PPV, and NPV of 78%, 76.2%, 76.6%, and 77.6%, respectively. CONCLUSIONS: Combined clinical parameters improved the localization diagnostic value of 18F-FDG PET/CT in the local uptake lesion subgroup and the etiological diagnostic value in the non-specific abnormal uptake subgroup.

Phenotypic characterization of macrophages in the BMB sample of human acute leukemia.

Macrophages within tissues display a strong plastic ability in respond to environmental cues in both physiologic influences and disease. However, the macrophage phenotype and its distribution in the bone marrow biopsies (BMB) samples of human acute leukemia (AL) remain poorly understood. In this study, 97 BMB samples of patients with acute leukemia and 30 iron-deficiency anemias (IDA) as control group were evaluated with immunohistochemistry. In comparison with controls, the counts of CD68+, CD163+, and CD206+macrophages were remarkably increased in BMB samples of acute leukemia (P < 0.01), as well as their infiltration density was roaring up-regulation (P < 0.01). The expression levels of CD68+, CD163+, and CD206+macrophages were decreased in patients with complete remission, but there still existed statistically significant contrast to the control group (P < 0.01). The ratios of the CD163-positive cells or CD206-positive cells to CD68-positive cells were most prevalent in the BMB samples of human acute leukemia compared with the control group (P < 0.01), which support that macrophages were polarized to M2 macrophages.

Plasma metabolomic and lipidomic alterations associated with COVID-19.

The pandemic of the coronavirus disease 2019 (COVID-19) has become a global public health crisis. The symptoms of COVID-19 range from mild to severe, but the physiological changes associated with COVID-19 are barely understood. In this study, we performed targeted metabolomic and lipidomic analyses of plasma from a cohort of patients with COVID-19 who had experienced different symptoms. We found that metabolite and lipid alterations exhibit apparent correlation with the course of disease in these patients, indicating that the development of COVID-19 affected their whole-body metabolism. In particular, malic acid of the TCA cycle and carbamoyl phosphate of the urea cycle result in altered energy metabolism and hepatic dysfunction, respectively. It should be noted that carbamoyl phosphate is profoundly down-regulated in patients who died compared with patients with mild symptoms. And, more importantly, guanosine monophosphate (GMP), which is mediated not only by GMP synthase but also by CD39 and CD73, is significantly changed between healthy subjects and patients with COVID-19, as well as between the mild and fatal cases. In addition, dyslipidemia was observed in patients with COVID-19. Overall, the disturbed metabolic patterns have been found to align with the progress and severity of COVID-19. This work provides valuable knowledge about plasma biomarkers associated with COVID-19 and potential therapeutic targets, as well as an important resource for further studies of the pathogenesis of COVID-19.

Design, synthesis, and preliminary biological evaluation of chrysin amino acid derivatives that induce apoptosis and suppress cell migration.

Amino acid derivatives containing chrysin were synthesized for evaluating their anticancer effects. Among them, compound N-(7-((5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl)oxy)heptanoyl)-L-isoleucine (6e) displayed the most potent antiproliferative activity against MGC-803 cells with IC50 value of 20.0 µM. Preliminary mechanistic studies showed that compound 6e could inhibit the colony formation and migration of MGC-803 cells. Flow cytometry analysis demonstrated that compound 6e mediated cell apoptosis of MGC-803 cells and arrested cell cycle in G2/M-phase. Moreover, 6e treatment in MGC-803 cells downregulated anti-apoptotic protein Bcl-2 and upregulated pro-apoptotic gene Bax in a concentration-dependent manner. Our studies suggest that compound 6e may sever as an effective chemotherapeutic candidate. [Formula: see text].

A Diagnostic Tool for Identification of Etiologies of Fever of Unknown Origin in Adult Patients.

The diagnosis and treatment of fever of unknown origin (FUO) are huge challenges to clinicians. Separating the etiologies of FUO into infectious and non-infectious disease is conducive to clinical physicians not only on making decisions rapidly concerning the prescription of suitable antibiotics but also on further analysis of the final diagnosis. In order to develop and validate a diagnostic tool to efficiently distinguish the etiologies of adult FUO patients as infectious or non-infectious disease, FUO patients from the departments of infectious disease and internal medicine in three Chinese tertiary hospitals were enrolled retrospectively and prospectively. By using polynomial logistic regression analysis, the diagnostic formula and the associated scoring system were developed. The variables included in this diagnostic formula were from clinical evaluations and common laboratory examinations. The proposed tool could discriminate infectious and non-infectious causes of FUO with an area under receiver operating characteristic curve (AUC) of 0.83, sensitivity of 0.80 and specificity of 0.75. This diagnosis tool could predict the infectious and non-infectious causes of FUO in the validation cohort with an AUC of 0.79, sensitivity of 0.79 and specificity of 0.70. The results suggested that this diagnostic tool could be a reliable tool to discriminate between infectious and non-infectious causes of FUO.

Effects of storage culture media, temperature and duration on human adipose­derived stem cell viability for clinical use.

Adipose­derived stem cells (ADSCs) are mesenchymal stem cells that are often used in regenerative medicine. Maintaining ADSC viability is important, as this optimizes the curative effects of cell therapy. However, the optimal conditions for cell viability preservation remain unknown. The present study aimed to acquire a better protocol for ADSC storage by comparing the effects of various solutions and temperatures for ADSC preservation, in order to suggest the most effective methods of short­term ADSC preservation for clinical use. ADSCs from passage 2 were suspended in solutions comprising 0.9% NaCl, 10% human serum (HS) or 10% platelet­rich plasma (PRP). Suspended cells were maintained at 4˚C or room temperature (~26˚C) for 2, 4 and 6 h. The differentiation capacity, apoptosis and proliferation of ADSCs were determined by oil red O/alizarin red S staining, flow cytometry, and a cell counting kit­8 cell proliferation assay, respectively. In addition, reverse transcription­quantitative polymerase chain reaction and western blot analysis was performed. The results revealed that proliferation of ADSCs decreased with time. The optimal time for ADSC use was ~2 h, and 4 h was determined to be the latest time that ADSCs should be used. The 10% HS group had the highest survival rate, followed by the 10% PRP group; these two groups had higher survival rates than the 0.9% NaCl group (P<0.05). HS and PRP at 4˚C enhanced the ADSC proliferation rate (P<0.05), although the difference between these two groups was insignificant (P>0.05). In conclusion, the optimal time to use ADSCs was <2 h, and should not exceed 4 h. It was recommended that, for the transportation and short­term storage of ADSCs during clinical use, they should be stored with 10% HS at 4˚C to maintain ADSC viability. In addition, this was a cost­effective and safe method.

Establishment of a Predictive Model Related to Pathogen Invasion for Infectious Diseases and Its Diagnostic Value in Fever of Unknown Origin.

The present study aimed to establish a list of parameters indicative of pathogen invasion and develop a predictive model to distinguish the etiologies of fever of unknown origin (FUO) into infectious and non-infectious causes. From January 2014 to September 2017, 431 patients with FUO were prospectively enrolled in the study population. This study established a list of 26 variables from the following 4 aspects: host factors, epidemiological factors, behavioral factors, and iatrogenic factors. Predefined predicted variables were included in a multivariate logistic regression analysis to develop a predictive model. The predictive model and the corresponding scoring system were developed using data from the confirmed diagnoses and 9 variables were eventually identified. These factors were incorporated into the predictive model. This model discriminated between infectious and non-infectious causes of FUO with an AUC of 0.72, sensitivity of 0.71, and specificity of 0.63. The predictive model and corresponding scoring system based on factors concerning pathogen invasion appear to be reliable screening tools to discriminate between infectious and non-infectious causes of FUO.

Applied value of monitoring serum hepcidin in differential diagnosis of infection versus tumor fevers.

The applied value of serum hepcidin in differential diagnosis of infection fevers versus tumor fevers was explored. A total of 432 fever patients were selected according to the domestic fever of unknown origin (FUO) diagnostic criteria from our hospital between June 2010 and November 2013. Venous blood samples were taken on the day 1, 5, 10 after admission. The infection group (98 cases) and the tumor group (50 cases) were set up based on the clinical and laboratory findings. ELISA was used to determine the serum hepcidin and IL-6 levels. SPSS 13.0 was used for statistical analysis. Hepcidin showed obvious descending trend on the 10th day in both the bacterial infection group (66 cases) and the virus infection group (32 cases), and the descending trend was similar to that of inflammatory indexes such as procalcitonin (PCT), hypersensitive C-reactive protein (h-CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC), and ferritin. Serum hepcidin showed no obvious differences in the tumor group on the day 1, 5, 10 after admission. In the infection groups, serum hepcidin was positively correlated with IL-6 (r=0.687, P=0.000) and CRP (r=0.487, P=0.026), but had a poor correlation with blood sedimentation, ferritin, PCT and WBC (P>0.05). Monitoring dynamic changes of hepcidin and related inflammatory factors in patients with fever is expected to be used for clinical identification of infection fever and tumor fever.

Baseline HBV load increases the risk of anti-tuberculous drug-induced hepatitis flares in patients with tuberculosis.

Hepatitis associated anti-tuberculous treatment (HATT) has been a main obstacle in managing patients co-infected with Mycobacterium tuberculosis and hepatitis B virus (HBV). Therefore, we evaluated the factors related to the severity of adverse effects during HATT, especially those associated with liver failure. A retrospective study was carried out at Tongji Hospital from 2007 to 2012. Increases in serum transaminase levels of >3, 5, and 10 times the upper limit of normal (ULN) were used to define liver damage as mild, moderate, and severe, respectively. Patients with elevated total bilirubin (TBil) levels that were more than 10 times the ULN (>171 µmol/L) with or without decreased (<40%) prothrombin activity (PTA) were diagnosed with liver failure. A cohort of 87 patients was analyzed. The incidence of liver damage and liver failure was 59.8% (n=52) and 25.3% (n=22), respectively. The following variables were correlated with the severity of hepatotoxicity: albumin (ALB) levels, PTA, platelet counts (PLT), and the use of antiretroviral therapies (P<0.05). Hypo-proteinemia and antiretroviral therapy were significantly associated with liver failure, and high viral loads were a significant risk factor with an odds ratio (OR) of 2.066. Judicious follow-up of clinical conditions, liver function tests, and coagulation function, especially in patients with high HBV loads and hypoalbuminemia is recommended. It may be advisable to reconsider the use of antiviral drugs failure during the course of anti-tuberculous treatment of HBV infection patients to avoid the occurrence of furious liver failure.

Baseline HBV Load Increases the Risk of Anti-tuberculous Drug-induced Hepatitis Flares in Patients with Tuberculosis / 华中科技大学学报（医学）（英德文版）

Hepatitis associated anti-tuberculous treatment (HATT) has been a main obstacle in managing patients co-infected with Mycobacterium tuberculosis and hepatitis B virus (HBV).Therefore,we evaluated the factors related to the severity of adverse effects during HATT,especially those associated with liver failure.A retrospective study was carried out at Tongji Hospital from 2007 to 2012.Increases in serum transaminase levels of＞3,5,and 10 times the upper limit of normal (ULN) were used to define liver damage as mild,moderate,and severe,respectively.Patients with elevated total bilirubin (TBil) levels that were more than 10 times the ULN (＞171 μrnol/L) with or without decreased (＜40％) prothrombin activity (PTA) were diagnosed with liver failure.A cohort of 87 patients was analyzed.The incidence of liver damage and liver failure was 59.8％ (n=52) and 25.3％ (n=22),respectively.The following variables were correlated with the severity of hepatotoxicity:albumin (ALB) levels,PTA,platelet counts (PLT),and the use of antiretroviral therapies (P＜0.05).Hypo-proteinemia and antiretroviral therapy were significantly associated with liver failure,and high viral loads were a significant risk factor with an odds ratio (OR) of 2.066.Judicious follow-up of clinical conditions,liver function tests,and coagulation function,especially in patients with high HBV loads and hypoalbuminemia is recommended.It may be advisable to reconsider the use of antiviral drugs failure during the course of anti-tuberculous treatment of HBV infection patients to avoid the occurrence of furious liver failure.

Applied Value of Monitoring Serum Hepcidin in Differential Diagnosis of Infection versus Tumor Fevers / 华中科技大学学报（医学）（英德文版）

The applied value of serum hepcidin in differential diagnosis of infection fevers versus tumor fevers was explored.A total of 432 fever patients were selected according to the domestic fever of unknown origin (FUO) diagnostic criteria from our hospital between June 2010 and November 2013.Venous blood samples were taken on the day 1,5,10 after admission.The infection group (98 cases) and the tumor group (50 cases) were set up based on the clinical and laboratory findings.ELISA was used to determine the serum hepcidin and IL-6 levels.SPSS 13.0 was used for statistical analysis.Hepcidin showed obvious descending trend on the 10th day in both the bacterial infection group (66 cases) and the virus infection group (32 cases),and the descending trend was similar to that of inflammatory indexes such as procalcitonin (PCT),hypersensitive C-reactive protein (h-CRP),erythrocyte sedimentation rate (ESR),white blood cell (WBC),and ferritin.Serum hepcidin showed no obvious differences in the tumor group on the day 1,5,10 after admission.In the infection groups,serum hepcidin was positively correlated with IL-6 (r=0.687,P=0.000) and CRP (r=0.487,P=0.026),but had a poor correlation with blood sedimentation,ferritin,PCT and WBC (P＞0.05).Monitoring dynamic changes of hepcidin and related inflammatory factors in patients with fever is expected to be used for clinical identification of infection fever and tumor fever.

Assessment of the Number and Phenotype of Macrophages in the Human BMB Samples of CML.

Macrophages have emerged as a key player in tumor biology. However, their number and phenotype in human bone marrow of biopsy (BMB) samples of chronic myeloid leukemia (CML) and their association with disease progression from an initial chronic phase (CP) to accelerated phase (AP) to advanced blast phase (BP) are still unclear. BMB samples from 127 CML patients and 30 patients with iron-deficiency anemia (IDA) as control group were analyzed by immunohistochemistry. The expression levels of CD68, CD163, and CD206 in BMB samples of CML patients were significantly higher than those in the patients of control group (P < 0.01), and we observed that their positive expression was gradually elevated during the transformation of CML-CP to AP to BP (P < 0.01). However, the expressions of CD68, CD163, and CD206 in released group were downregulated and contrasted to these in control group; there exists statistical significance (P < 0.01). The percentage ratio of CD163 and CD206 to CD68 was pronounced to be increasing from CML-CP to AP to BP (P < 0.01). Hence, the higher proportion of CD68+, CD163+ and CD206+ macrophages in BMB samples can be considered a key factor for disease progression of CML patients. Targeting macrophages, especially the M2 phenotype may help in designing therapeutic strategies for CML.

Targeted exome sequencing reveals novel USH2A mutations in Chinese patients with simplex Usher syndrome.

BACKGROUND: Usher syndrome (USH) is an autosomal recessive disorder characterized by hearing impairment and vision dysfunction due to retinitis pigmentosa. Phenotypic and genetic heterogeneities of this disease make it impractical to obtain a genetic diagnosis by conventional Sanger sequencing. METHODS: In this study, we applied a next-generation sequencing approach to detect genetic abnormalities in patients with USH. Two unrelated Chinese families were recruited, consisting of two USH afflicted patients and four unaffected relatives. We selected 199 genes related to inherited retinal diseases as targets for deep exome sequencing. Through systematic data analysis using an established bioinformatics pipeline, all variants that passed filter criteria were validated by Sanger sequencing and co-segregation analysis. RESULTS: A homozygous frameshift mutation (c.4382delA, p.T1462Lfs*2) was revealed in exon20 of gene USH2A in the F1 family. Two compound heterozygous mutations, IVS47 + 1G > A and c.13156A > T (p.I4386F), located in intron 48 and exon 63 respectively, of USH2A, were identified as causative mutations for the F2 family. Of note, the missense mutation c.13156A > T has not been reported so far. CONCLUSION: In conclusion, targeted exome sequencing precisely and rapidly identified the genetic defects in two Chinese USH families and this technique can be applied as a routine examination for these disorders with significant clinical and genetic heterogeneity.

siRNA-mediated gene silencing of MexB from the MexA-MexB-OprM efflux pump in Pseudomonas aeruginosa.

To gain insights into the effect of MexB gene under the short interfering RNA (siRNA), we synthesized 21 bp siRNA duplexes against the MexB gene. RT-PCR was performed to determine whether the siRNA inhibited the expression of MexB mRNA. Changes in antibiotic susceptibility in response to siRNA were measured by the E-test method. The efficacy of siRNAs was determined in a murine model of chronic P. aeruginosa lung infection. MexB-siRNAs inhibited both mRNA expression and the activity of P. aeruginosa in vitro. In vivo, siRNA was effective in reducing the bacterial load in the model of chronic lung infection and the P. aeruginosa-induced pathological changes. MexB-siRNA treatment enhanced the production of inflammatory cytokines in the early infection stage (P＜0.05). Our results suggest that targeting of MexB with siRNA appears to be a novel strategy for treating P. aeruginosa infections.

Rotary self-locking intramedullary nail for long tubular bone fractures.

BACKGROUND: Intramedullary nails had been widely used in the treatment of long-bone fractures because of less interference of fractures and center bearing biomechanical advantage. However, it had been also found many shortcomings such as broken nails, delayed healing and was modified in order to achieve better efficacy and reduce complications. The aim of the present study is to compare the efficacy of rotary self-locking intramedullary nails (RSIN) with that of interlocking intramedullary nails (IIN) in the treatment of long-bone fractures. METHODS: A retrospective study investigated 129 cases with long-bone fractures (36 with femoral fracture, 81 with tibial fracture, and 12 with humeral fracture). The fractures were fixed using either an RSIN or IIN. All patients underwent followup for 12-30 months. RESULTS: All patients in both groups achieved a clinical fracture healing standard and the postoperative affected limb muscle strength and joint function were well restored. The RSIN group required a shorter operative time and the fracture healed faster. There was no significant difference in the hospital stay, intraoperative blood loss or postoperative complications between the two groups. CONCLUSIONS: RSIN is used to treat long-bone fractures. Its healing efficacy is equivalent to the IIN. Moreover, the RSIN method is simpler and causes less tissue damage than the IIN, therefore having the advantage of accelerated healing.