Efficacy of rituximab-containing regimens used as first-line and rescue therapy for giant cell hepatitis with autoimmune hemolytic anemia a retrospective study.

OBJECTIVE: To evaluate the efficacy of rituximab (RTX)-containing therapy as first-line as well as rescue treatment for giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA). METHODS: This retrospective study recruited patients diagnosed with GCH-AHA and treated with conventional immunosuppressor regimens consisting of prednisone or RTX-containing regimes consisting of RTX and prednisone, with or without another immunosuppressor. The primary outcomes were the complete remission (CR) rate and time-period required for CR. The secondary outcomes included relapses and adverse events. RESULTS: Twenty patients (8 females and 12 males; age range 1-26 months), 15 receiving conventional regimens and 5 receiving RTX-containing regimens, were included. The CR rates were 73.3 % (11/15) and 100 % (5/5) in the conventional and RTX-containing groups, respectively. The time-period required for CR was significantly shorter in the RTX-containing group than in the conventional group (6 (3-8) versus 14 (5-25) months, P = 0.015). Relapses occurred in 30.8 % (4/13) of patients in the conventional group; all achieved CR after adding RTX. Relapses occurred in 40.0 % (2/5) of patients in the RTX-containing group; both achieved CR after adding intravenous immune globulins or tacrolimus. Transient low immunoglobulin and infections were recorded in both groups. Treatment withdrawal was achieved in 73.3 % (11/15) and 60.0 % (3/5) of patients receiving conventional and RTX-containing regimens after 36 (2-101) and 22 (4-41) months, respectively. Two patients in conventional group died of disease progression and infection. CONCLUSIONS: RTX-containing first-line therapy achieves CR of GCH-AHA more quickly than the conventional therapy. RTX is efficacious when added to rescue therapy.

Ability of lactulose breath test results to accurately identify colorectal polyps through the measurement of small intestine bacterial overgrowth.

BACKGROUND: While colorectal polyps are not cancerous, some types of polyps, known as adenomas, can develop into colorectal cancer over time. Polyps can often be found and removed by colonoscopy; however, this is an invasive and expensive test. Thus, there is a need for new methods of screening patients at high risk of developing polyps. AIM: To identify a potential association between colorectal polyps and small intestine bacteria overgrowth (SIBO) or other relevant factors in a patient cohort with lactulose breath test (LBT) results. METHODS: A total of 382 patients who had received an LBT were classified into polyp and non-polyp groups that were confirmed by colonoscopy and pathology. SIBO was diagnosed by measuring LBT-derived hydrogen (H) and methane (M) levels according to 2017 North American Consensus recommendations. Logistic regression was used to assess the ability of LBT to predict colorectal polyps. Intestinal barrier function damage (IBFD) was determined by blood assays. RESULTS: H and M levels revealed that the prevalence of SIBO was significantly higher in the polyp group than in the non-polyp group (41% vs 23%, P < 0.01; 71% vs 59%, P < 0.05, respectively). Within 90 min of lactulose ingestion, the peak H values in the adenomatous and inflammatory/hyperplastic polyp patients were significantly higher than those in the non-polyp group (P < 0.01, and P = 0.03, respectively). In 227 patients with SIBO defined by combining H and M values, the rate of IBFD determined by blood lipopolysaccharide levels was significantly higher among patients with polyps than those without (15% vs 5%, P < 0.05). In regression analysis with age and gender adjustment, colorectal polyps were most accurately predicted with models using M peak values or combined H and M values limited by North American Consensus recommendations for SIBO. These models had a sensitivity of ≥ 0.67, a specificity of ≥ 0.64, and an accuracy of ≥ 0.66. CONCLUSION: The current study made key associations among colorectal polyps, SIBO, and IBFD and demonstrated that LBT has moderate potential as an alternative noninvasive screening tool for colorectal polyps.

YTHDF3 mediates HNF1α regulation of cervical cancer radio-resistance by promoting RAD51D translation in an m6A-dependent manner.

Radiotherapy, as an important primary treatment, has effectively improved the survival of patients with cervical cancer (CC). Some patients, however, do not benefit optimally from radiotherapy because of radio-resistance. Therefore, identifying radio-resistance biomarkers and unravelling the underlying mechanisms is of critical importance for these patients. In the present study, we found significant upregulation of hepatocyte nuclear factor 1-alpha (HNF1α) expression in radio-resistant cervical cancer tissues and cell lines. Depletion of HNF1α reduced and overexpression of HNF1α promoted the resistance of CC cells to irradiation in vitro and in vivo. HNF1α positively regulated DNA repair protein RAD51 homologue 4 (RAD51D) at the protein level but not at the mRNA level. Mechanistically, upregulation of HNF1α enhanced YTH domain-containing family protein 3 (YTHDF3) transcription, which in turn promoted RAD51D mRNA N6 -methyladenosine (m6A) modification. YTHDF3 mediates HNF1α regulation of cervical cancer radio-resistance by promoting RAD51D translation in an m6A-dependent manner. The HFN1α/YTHDF3/RAD51D regulatory axis was found to play a critical role in conferring radio-resistance of CC cells. In conclusion, dysregulation of the HFN1α/YTHDF3/RAD51D axis may promote the radio-resistance of CC cells. Blocking this pathway may provide therapeutic benefits against CC radio-resistance.

Construction of a predictive model of abdominal lymph node metastasis in thoracic esophageal squamous cell carcinoma and preliminary analysis of its effect on target for postoperative radiotherapy.

Purpose: To investigate the influencing factors of abdominal lymph node metastasis in thoracic esophageal squamous cell carcinoma (TESCC), and to construct its predictive model, in order to analyze the targets for postoperative radiotherapy. Methods and materials: From January 2008 to December 2014, the clinicopathological data of 479 patients who underwent radical resection for esophageal cancer in the Fourth Hospital of Hebei Medical University were collected and retrospectively analyzed. The influencing factors of postoperative abdominal lymph node metastasis were analyzed, and a predictive model was constructed based on their independent influencing factors. Receiver operating characteristic (ROC) curve was utilized to analyze the predictive value of this model; in the meantime, the postoperative locoregional recurrence (LRR) of this group was analyzed. Results: The postoperative pathology of all patients showed that the lymph node metastasis rate (LNR) was 39.7%, of which the abdominal lymph node metastasis rate was 22.0%. Logistic regression analysis revealed that the patient's lesion location, pN stage, vascular invasion, LND and mediastinal lymph node metastasis were independent risk factors for the positive rate of abdominal lymph nodes after surgery (P = 0.000, 0.000, 0.033, 0.000, 0.000). The probability of abdominal lymph node metastasis was Y = ex/(1 + ex), and X = -5.502 + 1.569 × lesion location + 4.269 × pN stage + 1.890 × vascular invasion + 1.950 × LND-4.248 × mediastinal lymph node metastasis. The area under the ROC curve (AUC) of this model in predicting abdominal lymph node metastasis was 0.962 (95% CI, 0.946-0.977). This mathematical model had a high predictive value for the occurrence of abdominal lymph node metastasis (P = 0.000), and the sensitivity and specificity of prediction were 94.6% and 88.3% respectively. The overall survival rate was significantly higher (X2 = 29.178, P = 0.000), while abdominal lymph node recurrence rate was lower in patients with negative abdominal lymph nodes than in those with negative lymph nodes (1.4%&7.7%, X2 = 12.254, P = 0.000). Conclusion: The lesion location, pN stage, vascular invasion, LND and mediastinal lymph node metastasis are independent influencing factors of abdominal lymph node metastasis in patients with TESCC. The mathematical model constructed by these indicators can accurately predict abdominal lymph node metastasis, which can help clinicians to choose the targets for postoperative radiotherapy.

Identifying patients with EVEN-plus syndrome using exome sequencing and clinical feature analysis: A case report.

BACKGROUND: The EVEN-plus syndrome (epiphyseal-vertebral-ear-nose dysplasia plus associated findings) is an extremely rare autosomal recessive inherited disease characterised by specific facial features and skeletal dysplasia. It has a prenatal onset due to defects in the HSPA9 gene. The syndrome has not been reported previously in China. METHODS: This study reported the characteristics, examination results, diagnosis and treatment of a female case aged 3 years and 3 months. RESULTS: The patient had global developmental delay and specific facial features, including a prominent forehead, a bilateral auricle deformity, a collapsed nose, a high palatine arch, a short neck and other appearance abnormalities. Her hip joint magnetic resonance imaging (MRI) results showed bilateral femoral head epiphyseal dysplasia with a fork-shaped malformation at the distal end, and her brain MRI showed white matter myelin dysplasia. HSPA9 compound heterozygous variants c.882_c.883delAG and c.613A>G were identified by exome sequencing. CONCLUSIONS: This finding expands the spectra of EVEN-plus syndrome phenotype and pathogenic variants and suggests that c.882_c.883delAG may have a higher distribution frequency in East Asian populations.

Efficacy and Safety of Washed Microbiota Transplantation to Treat Patients with Mild-to-Severe COVID-19 and Suspected of Having Gut Microbiota Dysbiosis: Study Protocol for a Randomized Controlled Trial.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is often accompanied by gastrointestinal symptoms, which are related to gut microbiota dysbiosis (GMD). Whether washed microbiota transplantation (WMT) is an effective treatment for COVID-19 patients suspected of having GMD by restoring the gut microbiota is unknown. This study is designed to explore the efficacy and safety of WMT in COVID-19 patients suspected of having GMD. METHODS: This is a randomized, multicenter, single-blind prospective study. COVID-19 patients suspected of having GMD will be randomly divided to receive routine treatment only or to receive routine treatment and WMT. The frequency of WMT will be once a day for three consecutive days. Laboratory and imaging examinations will be performed at admission, 1 and 2 weeks after treatment, and on the day of discharge. Then a telephone follow-up will be conducted at 1st week, 2nd week, and 6th month after discharge. The clinical efficacy and safety of WMT in COVD-19 patients suspected of having GMD and the effects of WMT on the organ function, homeostasis, inflammatory response, intestinal mucosal barrier function, and immunity of the patients will be evaluated. RESULTS: By following the proposed protocol, WMT is expected to be efficacious and safe for the treatment of COVID-19 patients suspected of having GMD, and the therapeutic effect is expected to be associated with improvement of the intestinal mucosal barrier function, inflammatory response, and immunity. CONCLUSION: The findings from this study may offer a new approach for the prevention and treatment of COVID-19 patients suspected of having GMD.

Preliminary analysis of the benefits of different irradiation types on patients with postoperative locoregional recurrence of esophageal cell squamous carcinoma.

BACKGROUND: To explore the benefits of different types of irradiation on patients with postoperative locoregional recurrence (LRR) of thoracic esophageal squamous cell carcinoma (ESCC). METHODS: We analyzed the medical records of 344 patients with recurrent esophageal cancer (EC) at the Fourth Hospital of Hebei Medical University. All patients met an inclusion criteria that included having postoperative LRR (without distant metastasis), and having received either chemotherapy, radiotherapy, or chemoradiotherapy after LRR. Patients either received elective nodal irradiation (ENI) or involved field irradiation (IFI), with a stratified analysis performed on both groups. SPSS 19.0 software (IBM Corporation, Armonk, NY USA) was then used for statistical analysis. RESULTS: The median overall survival time of all patients after surgery was 33 months [95% confidence interval (CI): 28.3-37.7 months]; the median overall survival time of patients after recurrence after radiotherapy was 12.8 months (95% CI: 11.3-14.3 months). There were 276 cases (80.2%) of single local recurrence after surgery, and 68 cases (19.8%) of multiple local recurrence (≥2). The results of our multivariate analysis showed that the patient's gender, log odds of positive lymph nodes (LODDS), and the number of courses of chemotherapy were all independent factors affecting the patient's prognosis (P=0.003, P<0.001, and P<0.001). The results of stratified analysis showed that patients with esophageal lesion length <5.0 cm, stage N0, ≤9 surgically dissected lymph nodes, no positive regional lymph node metastasis (LNM), and LODDS ≤0.030 could benefit from ENI treatment (X2=4.208, P=0.032; X2=6.262, P=0.012; X2=10.359, P=0.001; X2=6.327, P=0.012; X2=6.026, P=0.014); and patients with ≥16 surgically dissected lymph nodes could benefit from IFI treatment (X2=4.429, P=0.035). CONCLUSIONS: Chemotherapy, radiotherapy, and chemoradiotherapy are all effective modes of treatment for patients with postoperative LRR of EC. Patients with shorter esophageal lesions determined by preoperative esophagography, earlier postoperative pathological N staging, lower LODDS scores, and fewer surgically dissected lymph nodes might benefit more from ENI treatment than from IFI. However, patients with a larger number of lymph nodes dissected during surgery might benefit more from IFI treatment. To further confirm this study's conclusions, multiple prospective studies should be undertaken in the future.

Pediatric Wilson disease presenting as acute liver failure: Prognostic indices.

BACKGROUND: Acute liver failure (ALF) can be a primary presentation of Wilson disease (WD). Mortality rates are high in WD with ALF (WDALF). Predictions of mortality in WDALF vary by model and are sometimes contradictory, perhaps because few patients are studied or WD diagnoses are questionable. AIM: To determine the outcomes among well-documented WDALF patients and assess mortality model performance in this cohort. METHODS: We reviewed the medical records of our pediatric WDALF patients (n = 41 over 6-years-old, single-center retrospective study) and compared seven prognostic models (King's College Hospital Criteria, model for end-stage liver disease/pediatric end-stage liver disease scoring systems, Liver Injury Unit [LIU] using prothrombin time [PT] or international normalized ratio [INR], admission LIU using PT or INR, and Devarbhavi model) with one another. RESULTS: Among the 41 Han Chinese patients with ALF, WD was established by demonstrating ATP7B variants in 36. In 5 others, Kayser-Fleischer rings and Coombs-negative hemolytic anemia permitted diagnosis. Three died during hospitalization and three underwent liver transplantation (LT) within 1 mo of presentation and survived (7.3% each); 35 (85.4%) survived without LT when given enteral D-penicillamine and zinc-salt therapy with or without urgent plasmapheresis. Parameters significantly correlated with mortality included encephalopathy, coagulopathy, and gamma-glutamyl transpeptidase activity, bilirubin, ammonia, and serum sodium levels. Area under the receiver operating curves varied among seven prognostic models from 0.981 to 0.748 with positive predictive values from 0.214 to 0.429. CONCLUSION: WDALF children can survive and recover without LT when given D-penicillamine and Zn with or without plasmapheresis, even after enlisting for LT.

Mitochondrial dysfunction resulting from the down-regulation of bone morphogenetic protein 5 may cause microtia.

BACKGROUND: Bone morphogenetic protein 5 (BMP5) has been identified as one of the important risk factors for microtia; however, the link between them has yet to be clarified. In this study, we aimed to demonstrate the relationship of BMP5 with mitochondrial function and investigate the specific role of mitochondria in regulating microtia development. METHODS: BMP5 expression was measured in auricular cartilage tissues from patients with and without microtia. The effects of BMP5 knockdown on cellular function and mitochondrial function were also analyzed in vitro. Changes in genome-wide expression profiles were measured in BMP5-knockdown cells. Finally, the specific impact of BMP5 down-regulation on mitochondrial fat oxidation was analyzed in vitro. RESULTS: BMP5 expression was down-regulated in the auricular cartilage tissues of microtia patients. BMP5 down-regulation inhibited various cellular functions in vitro, including cell proliferation, mobility, and cytoactivity. The functional integrity of mitochondria was also damaged, accompanied by a decrease in mitochondrial membrane potential, reactive oxygen species (ROS) neutralization, and reduced adenosine triphosphate (ATP) production. Carnitine O-palmitoyltransferase 2 and diacylglycerol acyltransferase 2, two of the key regulators of mitochondrial lipid oxidation, were also found to be decreased by BMP5 down-regulation. CONCLUSIONS: Down-regulation of BMP5 affects glycerolipid metabolism and fatty acid degradation, leading to mitochondrial dysfunction, reduced ATP production, and changes in cell function, and ultimately resulting in microtia. This research provides supporting evidence for an important role of BMP5 down-regulation in affecting mitochondrial metabolism in cells, and sheds new light on the mechanisms underlying the pathogenesis of microtia.

Changes in oral flora of patients with functional dyspepsia.

To explore the changes in oral flora in people with functional dyspepsia (FD). Unstimulated saliva was collected from 21 FD patients diagnosed according to the Rome IV criteria and from 12 healthy controls (HCs) for 16SrRNA sequencing. The pH of saliva samples and community periodontal index (CPI) were tested. The prevalence of small intestinal bacterial overgrowth (SIBO) was obtained by the methane-and hydrogen-based breath test. At the phylum level, FD patients had a higher relative abundance of Spirochaetes and a lower relative abundance of Fusobacteria, TM7 and Proteobacteria than HCs (p < 0.01). In the saliva, Kingella and Abiotrophia genus levels showed significant changes between the FD and HC groups (p < 0.01). Salivary species level marker Intermedia was significantly different between FD and HC groups (p < 0.01). The oral pH of FD patients was higher than that of HCs (p < 0.01). The mean CPI of the FD group was 1.52 and that of the HC group was 0.17 (p < 0.01). Moreover, 71.4% of the FD group was positive for SIBO. The oral flora of FD patients was different from that of HCs. Spirochaetes, Kingella, Abiotrophia, and Intermedia may be diagnostic indicators of FD.

Knockdown of FAM83D Enhances Radiosensitivity in Coordination with Irradiation by Inhibiting EMT via the Akt/GSK-3ß/Snail Signaling Pathway in Human Esophageal Cancer Cells.

PURPOSE: To explore the effects of FAM83D on the proliferation, invasion and radiosensitivity of human esophageal cancer cells and to elucidate the mechanism involved in the regulation of the growth and metastasis of esophageal cancer cells. METHODS AND MATERIALS: This study included sixty-nine patients with esophageal cancer. The expression levels of FAM83D in the esophageal cancer tissues and paracarcinoma tissues of the sixty-nine patients were measured. We also examined FAM83D expression in five cell lines. We analyzed the effects of FAM83D on the proliferation, invasion and radiosensitivity of human esophageal cancer cells via MTS, Transwell, and colony formation assays. The effect of FAM83D knockdown on cell apoptosis was assayed by flow cytometry. In addition, we also examined changes in the expression of metastasis-related molecules at the protein and mRNA levels by qRT-PCR and Western blotting after silencing FAM83D expression, and we detected the expression of PI3K/Akt signaling-related proteins by Western blotting. RESULTS: The results demonstrated that the expression of FAM83D was obviously higher in esophageal cancer tissues and cell lines than that in human adjacent normal tissues and normal esophageal epithelial cell lines. FAM83D overexpression was positively associated with tumor size, tumor-node-metastasis (TNM) stage, T classification, N classification, distant metastasis and relapse and was negatively associated with patient survival rates. FAM83D shRNA transfection suppressed its expression. Compared to that in the control group, the proliferation of tumor cells in the FAM83D shRNA group was hindered after exposure to radiation in vitro and in vivo; in addition, FAM83D knockdown inhibited cell invasion, induced apoptosis and regulated apoptosis-related protein expression. Moreover, the radiosensitivity of esophageal cancer cells was increased after depletion of FAM83D. In addition, FAM83D silencing was associated with the reversion of EMT, as reflected by an increase in the epithelial marker E-cadherin and a decrease in the mesenchymal markers N-cadherin and vimentin. Further study showed that FAM83D depletion suppressed the signaling pathway involving p-Akt, p-GSK-3ß and Snail. CONCLUSION: The results reveal that FAM83D may be a potential therapeutic target for esophageal squamous cell carcinoma (ESCC) and that lower expression of FAM83D in coordination with irradiation promotes the radiosensitization of ESCC by inducing EMT through the Akt/GSK-3ß/Snail signaling pathway.

[Spatial distribution characteristics and influencing factors of eco-environmental quality based on RS and GIS in Shiyang River Basin, China.] / 基于RS和GISçš„çŸ³ç¾Šæ²³æµåŸŸç”Ÿæ€çŽ¯å¢ƒè´¨é‡ç©ºé—´åˆ†å¸ƒç‰¹å¾åŠå ¶å½±å“å› ç´ .

Based on RS and GIS, 11 indexes from three aspects including natural capital, social pressure and economic supports were selected. The natural capital index (NCI), social pressure index (SPI), economic support index (ESI), and environment quality evaluation index (EQEI) were constructed by using spatial principal component analysis, variation coefficient method, and analytic hierarchy process. The spatial distribution characteristics and influencing factor of the environmental quality in Shiyang River Basin were analyzed. The results showed that the overall environmental quality was at poor level in Shiyang River Basin. The regions with better classes of environmental quality were mainly concentrated in the upper reaches of Qilian Mountains, and those with poorer classes were mainly concentrated in the middle-lower reaches of low hills land and desert. The EQEI value in Shiyang River Basin had polarization phenomenon from southwest to northeast. With the variation of distance, the value had large variation range, with obvious spatial heterogeneity. The environmental quality showed both high and low aggregation patterns, with "fault" distribution. There were highly clustered hot spots and highly clustered cold spots in the basin. Among the influen-cing factors of environmental quality, natural capital was the dominant one, social pressure was the second, and economic support was the least contributor.

BMI-1 suppression increases the radiosensitivity of oesophageal carcinoma via the PI3K/Akt signaling pathway.

B-cell­specific Moloney murine leukaemia virus integration site-1 (BMI-1) contributes to the growth of tumour cells post-irradiation (IR). The aim of the present study was to characterize the effects of BMI-1 on cell viability, radiosensitivity and its mechanisms of action in oesophageal squamous cell cancer (ESCC). Western blotting and immunohistochemistry were employed to evaluate the protein expression of BMI-1 in ESCC cells and specimens, respectively. Additionally, the protein expression levels of BMI-1, H2AK119ub and γH2AX in ESCC cells were detected following different doses of IR and at different times after IR. The protein expression levels of MDC1 and 53BP1 were also measured. Flow cytometry and MTT assays were used to determine cell cycle progression, apoptosis and cell viability. The phosphatidylinositol 3-kinase inhibitor LY294002 and the agonist IGF-1 were employed to suppress or induce the phosphorylation of Akt to determine whether BMI-1 induces radioresistance in ESCC cells via activation of the PI3K/Akt pathway. The expression of BMI-1 was higher in ESCC tissues and cells compared with that in normal oesophageal tissues and cells. In addition, BMI-1 was positively related to tumour size and lymph node metastases and negatively to the overall survival of ESCC patients. IR induced the expression of BMI-1, H2AK119ub and γH2AX in a dose- and time-dependent manner. BMI-1 knockdown lowered the expression of γH2AX, MDC1 and 53BP1, suppressed cell viability and increased radiosensitivity. G2/M phase arrest was eliminated; this was followed by an increased proportion of cells entering the G0/G1 phase after IR and BMI-1 knockdown via the upregulation of P16 and downregulation of cyclin D2 and cyclin-dependent kinase-4. Moreover, BMI-1 knockdown increased cell apoptosis, downregulated MCL-1 and p-Akt and upregulated Bax. Additionally, the inhibitory effect of the downregulation of p-Akt by LY294002 on tumour cell viability was identical to that of BMI-1 knockdown, while the kinase agonist IGF-1 reversed the effects of BMI-1 knockdown on cell viability and radiosensitivity. Taken together, BMI-1 knockdown induces radiosensitivity in ESCC and significantly inhibits cell viability, which may contribute to an increased proportion of cells in the G0/G1 phase and cell apoptosis via suppression of the PI3K/Akt signalling pathway.

Voice Therapy Effect on Mutational Falsetto Patients: A Vocal Aerodynamic Study.

OBJECTIVE: The study aims to evaluate the effectiveness of voice therapy (VT) and analyze the vocal aerodynamic characteristics in mutational falsetto (MF) patients. METHODS: From October 2010 through May 2014, 26 patients with MF at Sun Yat-sen Memorial Hospital were studied retrospectively. Vocal assessment, including the 10-item Voice Handicap Index (VHI-10), fundamental frequency (F0), and vocal aerodynamic parameters (subglottic pressure [SGP]), aerodynamic power [AP], mean expiratory airflow, and maximum phonation time [MPT]), was proceeded before and after VT. RESULTS: Before VT, the mean F0, AP, and SGP of MF patients were significantly higher than Control Group, whereas mean MPT was significantly shorter. After a 4-week VT, the mean F0, AP, and SGP were decreased, and the mean MPT was significantly increased compared with the measurements obtained before VT. After the 4-week VT, the VHI-10 scores in 21 patients reverted to normal Control Group's level (Effective Subgroup), whereas the VHI-10 scores in the other 5 patients remained higher than the normal Control Group (Ineffective Subgroup). Subgroup analysis showed the mean AP and SGP of the Ineffective Subgroup were similar to the Control Group, whereas the Effective Subgroup showed higher AP and SGP. After the 4-week VT, MPT in both the Effective Subgroup and Ineffective Subgroup increased significantly, but AP and SGP in the Ineffective Subgroup did not change significantly. CONCLUSION: VT is an effective treatment for MF patients with laryngeal hyperfunction. Most MF patients can return to normal voice in 4 weeks. Vocal aerodynamic examination can help in predicting the VT effect and deciding the treatment plan. MF patients without laryngeal hyperfunction may need longer VT period or other adjuvant treatment.

[Application and development of in vitro metabolism study at early drug discovery stage].

Drug metabolism studies, including in vivo and in vitro metabolism studies, are significant in the design of candidate compounds and screening of lead compounds at drug discovery/development stages. Compared with in vivo metabolism studies, in vitro metabolism studies have the advantages of rapidity, simplicity, without consumption of large amounts of samples and animals. Moreover, it is convenient for researchers to observe the selective interaction between compound and target. Therefore, in vitro metabolism studies are appropriate for high throughput screening of compounds which are lack of metabolism information and have been widely used during drug discovery stages. This article briefly introduced the application of in vitro drug metabolism studies based on the metabolic stability, reaction phenotyping and metabolic drug-drug interactions, aiming to raise valuable evaluation strategies for innovative drug discovery in China.

[Multi-center clinical study on the treatment of the low-middle frequency sudden hearing loss].

OBJECTIVE: To investigate and compare the short-term outcome of patients with low-middle frequency sudden deafness treated with alone or combination treatment. METHODS: From August 2007 to October 2011, 205 patients with the diagnosis of low-middle frequency sudden deafness who were from 33 different clinical centers were recruited. All patients were followed up for four weeks from the initial examination. Patients were treated with steroid , Ginaton, batroxobin respectively, or Ginaton and steroid combination treatment. RESULTS: The total effective rate was 90.73%. In Ginaton group, the total effective rate was 87.27%, 89.19% in steroid group, 87.80% in batroxobin group, and 95.83% in Ginaton and steroid group. Considering the total effective rate, there was no statistical difference between four groups (χ(2) = 7.98, P = 0.54). The clinical cure rate for steroid alone was 81.01%, Ginaton alone 76.36%, batroxobin alone 68.29%, and Ginaton and steroid combination treatment 80.56%. There were no clinically significant differences between the different treatments (P > 0.05). CONCLUSIONS: The low-middle frequency sudden deafness tends to have a relatively favorable prognosis. The steroid played a good effect in the treatment. But different treatments either improving the microcirculation of inner ear or alleviating edema blood has undifferentiated results. Therefore the combination therapy may be more effective.

[Survival analysis for laryngeal carcinoma patients with no surgery, radiotherapy or chemotherapy].

OBJECTIVE: To investigate the survival rate and prognostic factors of laryngeal carcinoma patients with no surgery, radiotherapy or chemotherapy. METHODS: One hundred and sixty-seven laryngeal carcinoma cases with no surgery, radiotherapy or chemotherapy were analyzed retrospectively. Survival rates were calculated by Kaplan-Meier product-limit method. With univariate analysis, comparisons among/between groups were performed using Log-rank test. Multivariate analysis was carried out using Cox proportional hazard model. RESULTS: Overall survival time was (16.0 ± 1.4) months (x(-) ± s), overall 1- and 2-year survival rates were 56.4% and 26.5%, respectively. No patient survived over 5 years in these cases who had been diagnosed more than 5 years (except for those who lost). Univariate analysis showed that primary site, pathological grade, T-stage, N-stage and clinical stage were significant prognostic factors for the survival of the patients (P < 0.05). The survival rates of laryngeal carcinoma whether with tracheotomy were no statistically significant (P > 0.05). Multivariate analysis showed survival rates statistically correlated with T stage and N stage (hazard ratio were 1.812 and 1.557, P < 0.05). CONCLUSIONS: The development of laryngeal carcinoma course was faster, without treatment to the tumor itself, even if palliative surgical such as tracheostomy would not improve the survival rate. In laryngeal carcinoma patients with no surgery, radiotherapy or chemotherapy, the factors affecting the survival rates include primary site, pathological grade, T-stage, N-stage and clinical stage, and of them, T-stage and N-stage are the independent prognostic factors.