In this article, the mechanism of inheritance behind inherited hearing loss and genetic susceptibility in noise-induced hearing loss are reviewed. Conventional treatments for sensorineural hearing loss (SNHL), i.e. hearing aid and cochlear implant, are effective for some cases, but not without limitations. For example, they provide little benefit for patients of profound SNHL or neural hearing loss, especially when the hearing loss is in poor dynamic range and with low frequency resolution. We emphasize the most recent evidence-based treatment in this field, which includes gene therapy and allotransplantation of stem cells. Their promising results have shown that they might be options of treatment for profound SNHL and neural hearing loss. Although some treatments are still at the experimental stage, it is helpful to be aware of the novel therapies and endeavour to explore the feasibility of their clinical application.
Animals ; Evidence-Based Practice ; Genetic Engineering ; Genetic Therapy ; Hearing Loss, Sensorineural ; genetics ; therapy ; Humans ; Mice ; Mice, Inbred C57BL ; Stem Cell Transplantation

BACKGROUNDSeveral studies have evaluated the association between polymorphisms of thymidylate synthase (TS) and cancer risk in diverse populations but with conflicting results. By pooling the relatively small samples in each study, it is possible to evaluate the association using a meta-analysis.

METHODSA comprehensive search was conducted to identify all case-control studies on TS on a 28-bp tandem repeats in 5'untranslated region (5'UTR) and a 6-bp insertion (ins) and deletion (del) mutation in 3'UTR of the gene and cancer risk. Meta-analysis was conducted using a fixed and random effect model.

RESULTSOur meta-analysis on a total of 13 307 cancer cases and 18 226 control subjects from 37 published case-control studies showed no significant association between the risk of cancer and the 5'UTR 28-bp tandem repeats polymorphism (3R/3R vs. 2R/2R: OR = 1.06, 95%CI, 0.93 - 1.20) or the 3'UTR 6-bp ins/del polymorphism (del6/del6 vs. ins6/ins6: OR = 0.93, 95%CI, 0.81 - 1.08) with significant between-study heterogeneity. In the cancer type- and ethnic subgroup-stratification analyses, we did not find any association between TS polymorphisms and cancer risk either.

CONCLUSIONTS 5'UTR 28-bp tandem repeats and 3'UTR 6-bp ins/del polymorphisms may not be associated with cancer risk.

3' Untranslated Regions ; genetics ; 5' Untranslated Regions ; genetics ; Case-Control Studies ; Genetic Predisposition to Disease ; genetics ; Humans ; Neoplasms ; epidemiology ; genetics ; Polymorphism, Genetic ; genetics ; Tandem Repeat Sequences ; genetics ; Thymidylate Synthase ; genetics

Zuojinwan originated from Danxi′s Experiential Therapy （《丹溪心法》） in the Yuan dynasty. It is a representative prescription for the treatment of liver fire invading stomach syndrome， and is also one of the typical prescriptions of the anti-adjuvant method of traditional Chinese medicine （TCM）. In this paper， the method of bibliometrics was used to systematically sort out the ancient books of Zuojinwan， and 729 relevant literature data were obtained. After certain retrieval and screening， 57 ancient books of TCM were finally obtained. The statistics and analysis were carried out from the aspects of prescription source， historical evolution， composition， functions， evolution of prescription meaning， prescription dose， and preparation and usage of Zuojinwan. It was found that Zuojinwan was composed of Coptis chinensis rhizoma and Euodia rutaecarpa fructus in a ratio of 6∶1. It was mainly used for the treatment of liver fire invading stomach syndrome. The symptoms included pain in chest and hypochondrium， vomiting and bitter mouth， noisy acid-swallowing， red tongue coating yellow， and pulse string number. Later medical records recorded that Zuojinwan was mostly consistent with the original prescription. It mainly treated various diseases caused by liver fire， including left by liver fire， including left hypochondriac pain， swallowing acid and vomiting acid， tendon hernia and lump， epigastric pain， bitter mouth pulse string， head pain， diarrhea， gonorrhea， cold and hot， abdominal pain， alcohol wet yellowing， silence of oral dysentery and so on. There was little controversy in the analysis of relevant prescriptions. In the past dynasties， pills was mainly used， which was consistent with the original prescription. In modern times， it is mainly water flooding for pills or steamed cakes for pills， warm boiling water to serve 6 g， taking 2-3 g per time， the history is basically the same. In this paper， through the excavation， collation and systematic analysis of the ancient literature of TCM that recorded Zuojinwan， we hope to provide the literature basis for the development， inheritance and utilization of this famous classical formulas.

Objective: To observe the effect of Pinelliae Rhizoma Praeparatum Cum Alumine polysaccharides(PRPCAP)on airway mucus secretion in rats with allergic asthma, in order to study the material basis of the "macromolecule" component of the polysaccharides as the original medicinal materials. Method: The 60 SPF-grade Wistar rats were induced by intraperitoneal injection of chicken ovalbumin (OVA) and aluminum-magnesium adjuvant, except for the normal control group. The OVA solution was aerosolized to establish a rat model of allergic asthma. After successful modeling, the rats were randomly divided into 5 groups, namely allergic asthma model group, positive drug group (montalurast sodium,5 mg·kg^-1), high-dose PRPCAP group (400 mg·kg^-1), middle-dose PRPCAP group (200 mg·kg^-1) and low-dose PRPCAP group (100 mg·kg^-1). The contents of interleukin-4 (IL-4) and interferon-γ (IFN-γ) in serum and bronchoalveolar lavage fluid (BALF) supernatant were determined by enzyme-linked immunosorbent assay (ELISA), and the count of eosinophils (EOS) was detected by BALF sediment. The histopathological changes were observed by hematoxylin-eosin (HE) staining in lung tissue. The mRNA expression of mucin 5AC (MUC5AC) was detected by Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR). Result: Compared with the normal control group, serum IL-4 level in the allergic asthma model group was significantly increased (P<0.01), IFN-γ level was significantly decreased (P<0.01), and EOS counts in BALF were significantly increased (P<0.01). Compared with the allergic asthma model group, the positive drug group, and high, middle, and low-dose PRPCAP groups could significantly reduce the serum IL-4 content (P<0.01), while high and middle-dose PRPCAP groups could significantly reduce the content of IL-4 in BALF (P<0.05, P<0.01), the middle-dose PRPCAP group could significantly increase the content of IFN-γ in serum (P<0.05), EOS counts in BALF were significantly lower in the positive drug group and all of PRPCAP groups (P<0.01). HE staining showed the pathological changes in the lung tissue of the allergic asthma model group and a mitigating effect in the positive drug group and all of PRPCAP groups. Compared with the normal control group, the expression of MUC5AC mRNA in the lung tissue of rats with allergic asthma was significantly increased (P<0.01). Compared with the model group of allergic asthma rats, the positive drug group and all of PRPCAP groups showed significant decrease in MUC5AC mRNA (P<0.01). Conclusion: The "macromolecule" component of polysaccharides in the Pinelliae Rhizoma Praeparatum Cum Alumine may be the material basis for the efficacy of eliminating dampness and eliminating phlegm.

From the perspective view of Chinese medicine, the Gan (Liver) meridian of Foot-Jueyin starts from the great toe, running upward along the medial side of the thigh to the perineal area, where it curves around the external genitalia and goes up to the lower abdomen. In clinical practice, acupoints in the feet of the Gan meridian of Foot-Jueyin are used to treat the genitourinary and external genitalia diseases. Studies have shown that reproductive system diseases have specific pathological reactions in the places (radial side of tibia and foot) where Gan meridian of Foot-Jueyin passes by. Why does this happen? In this article, we begin by briefly reviewing the evidences linking foot and genitalia. We then explore the potential mechanism of the relationship between genitals and the Gan meridian of Foot-Jueyin. The brain cerebral cortex is characterized by cortical interactions. Numerous studies show that different cerebral cortex function areas (especially the adjacent areas) are overlapping and interact with each other. Finally, we presume that there is a specific connection between the feet and the genitals. Physiologically in the cortical homunculus, the genital area lies adjacent or overlapped to the foot areas, the two areas may interact with each other. The functional reorganization between different areas of the cerebral cortex under pathological conditions may be the underlying mechanism of the relationship between the feet and the genitals.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.