The optimal intravesical maintenance chemotherapy scheme for the intermediate-risk group non-muscle-invasive bladder cancer.

OBJECTIVE: Although the current European Association of Urology(EAU) guideline recommends that patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) should accept intravesical chemotherapy or Calmette-Guerin (BCG) for no more than one year after transurethral resection of bladder tumor(TURBT), there is no consensus on the optimal duration of chemotherapy. Hence, we explored the optimal duration of maintenance intravesical chemotherapy in patients with intermediate-risk NMIBC. SUBJECTS AND METHODS: This was a real-world single-center retrospective cohort study. In total 158 patients with pathologically confirmed intermediate-risk NMIBC were included, who were divided into 4 subgroups based on the number of instillations given. We used Cox regression analysis and survival analysis chart to explore the 3-yr recurrence outcomes of tumor.The optimal duration was determined by receive operating characteristic curve (ROC). RESULTS: The median follow-up was 5.2 years. Compared with instillation for 1-2 months, the Hazard Ratios(HR) values of instillation for less than 1 month, maintenance instillation for 3-6 months and > 6 months were 3.57、1.57 and 0.22(95% CI 1.27-12.41;0.26-9.28;0.07-0.80, P = 0.03;0.62;0.02, respectively). We found a significant improvement in 3-yr relapse-free survival in intermediate-risk NMIBC patients who maintained intravesical instillation chemotherapy for longer than 6 months, and the best benefit was achieved with 10.5 months of maintenance chemotherapy by ROC. CONCLUSIONS: In our scheme, the optimal duration of intravesical instillation with pirrubicin is 10.5 months. This new understanding provides valuable experience for the precise medical treatment model of intermediate-risk NMIBC.

Dexmedetomidine Inhibits Inflammation to Alleviate Early Neuronal Injury via TLR4/NF-κB Pathway in Rats with Traumatic Brain Injury.

Purpose - This study aims to explore the potential mechanism of dexmedetomidine in terms of inhibiting inflammation to alleviate early neuronal injury via TLR4/NF-κB pathway in rats with traumatic brain injury. Methods - The model of brain injury was established in rats. After the model was established, the rats were randomly divided into five groups: Sham, Sham + DEX, TBI, TBI + vehicle, and TBI + DEX. Each group included 10 rats. The water content in the brain tissue was measured. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays were performed on histopathological tissue sections to evaluate neuronal apoptosis. Enzyme-linked immunosorbent assay and PCR were applied to detect the levels of the inflammatory factors, TNF-α, IL-1ß, IL-6, and NF-κB. Results - TBI-challenged rats exhibited significant neuronal apoptosis, which was characterized via the wet-to-dry weight ratio, neurobehavioral functions, TUNEL assay results, and the levels of cleaved caspase-3, Bax upregulation, and Bcl-2, which were attenuated by DEX. Western blot, immunohistochemistry, and PCR results revealed that DEX promoted TLR4 expression and upregulated expression of the TLR4 downstream factors, HO-1 and NQO-1. Furthermore, DEX treatment markedly prevented the downregulation of inflammatory response factors, TNF-α, IL-1ß and NF-κB, and IL-6. Conclusion - Dexmedetomidine is able to inhibit inflammation and attenuate early neuronal injury in rats with acute brain injury, which may act on TLR4/NF-κB pathway.

Prolonged preoperative fasting induces postoperative insulin resistance by ER-stress mediated Glut4 down-regulation in skeletal muscles.

Preoperative fasting aims to prevent pulmonary aspiration and improve bowel preparation, but it may induce profound systemic catabolic responses that lead to protein breakdown and insulin-resistant hyperglycemia after operation. However, the molecular mechanisms of catabolic reaction induced by prolonged preoperative fasting and surgical stress are undetermined. In this study, anesthetized rats were randomly assigned to receive a sham operation or laparotomy cecectomy. Fasting groups were restricted from food and water for 12 h before operation, while the feeding group had free access to food throughout the study period. Twenty-four hours after operation, the animals were sacrificed to collect blood samples and soleus muscles for analysis. Postoperative blood glucose level was significantly increased in the fasting group with elevated serum insulin and C-peptide. Continuous feeding reduced serum myoglobin and lactate dehydrogenase concentrations. Preoperative fasting activated inositol-requiring transmembrane kinase/endoribonuclease (IRE)-1α and c-Jun N-terminal kinase (JNK) mediated endoplasmic reticulum (ER)-stress, and reduced glucose transporter type 4 (Glut4) expression in the soleus muscle. Phospholamban phosphorylation was reduced and intracellular calcium levels were increased in the isolated skeletal muscle cells. Similar results were found in ER stress-induced C1C12 myoblasts. The expression of Glut4 was suppressed in the stressed C1C12, but was potentiated following inhibition of ER stress and chelation of intracellular free calcium. This study provides evidence demonstrating that prolonged preoperative fasting induces ER stress and generates insulin resistance in the skeletal muscle through suppression of Glut4 and inactivation of Ca2+-ATPase, leading to intracellular calcium homeostasis disruption and peripheral insulin resistance.

Involvement of Aquaporins in the Intense Pulsed Light-Enhanced Wound Healing in Diabetic Rats.

BACKGROUND AND OBJECTIVES: We previously demonstrated that intense pulsed light (IPL) irradiation prior to wounding improved the wound healing in rats with diabetes mellitus (DM). Also, we found that IPL upregulated the expression of aquaporin 3 (AQP3), a protein that is crucial for wound healing, in normal rats. This present study aimed to examine the involvement of AQPs in the IPL-enhanced wound healing in diabetic rats. STUDY DESIGN/MATERIALS AND METHODS: Streptozotocin was used to induce diabetes in Sprague-Dawley rats. Animals were divided into four groups: normal group, DM only group, DM rats with IPL treatment 2 weeks before wounding (DM + IPL-Pre group), and DM rats with concurrent IPL irradiation and wounding (DM + IPL-Con group). Wounds were created on the dorsal skin of rats. The expressions of AQP1, 3, 4, 7, and 9 in the pre-injured skin, periwound, and wound were determined. RESULTS: Among all the AQPs analyzed, only the expressions of AQP3 and AQP7 were significantly altered. Unirradiated diabetic rats showed much higher expression level of AQP3 in the regenerating skin compared with normal rats. IPL pretreatment, but not concurrent treatment, attenuated the expression toward the level detected in the normal wounds. In contrast, a lower expression level of AQP7 was noted in the regenerating skin of DM only rats and IPL pretreatment upregulated the expression to a level similar to that in the normal rats. CONCLUSION: The beneficial effect of IPL pretreatment on the wound healing in diabetic rats might involve a mechanism by which the expression of AQPs is regulated. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Beneficial Effect of Intense Pulsed Light on the Wound Healing in Diabetic Rats.

BACKGROUND AND OBJECTIVE: Wound healing in diabetes mellitus (DM) patients is one of the major health concerns globally. Intense pulsed light (IPL) has been widely used in cosmetic dermatology via mechanisms involving fibroblast stimulation, collagen synthesis, and dermal remodeling, which are events that also occur during the process of wound healing. This present study was aimed to evaluate the possible beneficial effect of IPL on the wound healing in diabetic rats. MATERIALS AND METHODS: Diabetes was induced in Sprague-Dawley rats using streptozotocin. The rats were randomly divided into four groups: normal group, DM only group, DM rats with IPL treatment 2 weeks before wounding (DM + IPL-Pre group), and DM rats with concurrent IPL exposure and wounding (DM + IPL-Con group). The wounds were created on the dorsal skin of rats. Wound closure rate, collagen deposition, and angiogenesis were assessed. RESULTS: There were no significant differences in the wound closure rate and mean time to wound closure between IPL-treated diabetic rats and normal rats. By contrast, delayed wound closure and prolonged mean time to wound closure were both noticed in DM only group. Enhanced collagen deposition and angiogenesis were observed in IPL-Pre, but not IPL-Con diabetic rats, as compared with untreated DM rats. CONCLUSION: Results of this study may provide novel insight into future preventive strategies using IPL for the management of wounds in diabetic patients. Lasers Surg Med. © 2019 Wiley Periodicals, Inc.

Value of tumor size as a prognostic factor in metastatic colorectal cancer patients after chemotherapy: a population-based study.

Aim: To evaluate the relationship between tumor size and survival in metastatic colorectal cancer (mCRC) patients who received chemotherapy. Materials & methods: SEER database was accessed for eligible patients. Multivariate Cox regression analysis was performed to compare the effect of tumor size on overall survival (OS) and CRC-specific survival (CCSS). Results: Tumor size ≥5 cm was an independent risk factor for OS and CCSS in mCRC patients treated with chemotherapy. Tumor size <5 cm did not show a survival advantage in patients whose primary tumor site was rectosigmoid junction, while tumor size ≥5 cm was associated with poor OS and CCSS in left-and right-sided colorectal cancer. Conclusion: Tumor size ≥5 cm was associated with poor prognosis after receiving chemotherapy treatment and a risk factor for survival of mCRC.

Expression of Protein 4.1 Family in Breast Cancer: Database Mining for 4.1 Family Members in Malignancies.

BACKGROUND The protein 4.1 family is a family of cytoskeletal proteins that play an important role in maintaining normal cell morphology and cell adhesion, migration, division, and intercellular signaling. The main aim of this study was to explore the prognostic significance of the protein 4.1 family in breast cancer (BC) patients and to provide new biomarkers and therapeutic targets for the diagnosis and treatment of BC. MATERIAL AND METHODS The expression of 4.1 family members in various tumor types was compared to normal controls using the ONCOMINE and GOBO databases. The prognostic significance of the 4.1 family in BC patients was determined by Kaplan-Meier Plotter. RESULTS EPB41L2 (4.1G) was expressed at higher levels in normal tissues compared with BC patients for all 4.1 family members. In survival analysis, 4.1G and EPB41 (4.1R) mRNA high expressions were associated with better survival in BC patients. Moreover, 4.1G high expression was significantly associated with longer overall survival (OS) in luminal A and protracted relapse-free survival (RFS) in luminal B subtype BC patients who received Tamoxifen treatment. In addition, high expression of each 4.1 family member also showed better prognostic value in different molecular subtypes of BC. CONCLUSIONS These results indicate that the protein 4.1 family can be regarded as novel biomarkers and potential therapeutic targets for BC. Further research is needed to explore the detailed biological functions.

Multi-Dimensional Spectrum-Effect Relationship of the Impact of Chinese Herbal Formula Lichong Shengsui Yin on Ovarian Cancer.

Lichong Shengsui Yin (LCSSY) is an effective and classic compound prescription of Traditional Chinese Medicines (TCMs) used for the treatment of ovarian cancer. To investigate its pharmacodynamic basis for treating ovarian cancer, the multi-dimensional spectrum-effect relationship was determined. Four compositions (I to IV) were obtained by extracting LCSSY successively with supercritical CO2 fluid extraction, 75% ethanol reflux extraction, and the water extraction-ethanol precipitation method. Nine samples for pharmacological evaluation and fingerprint analysis were prepared by changing the content of the four compositions. The specific proportions of the four compositions were designed according to a four-factor, three-level L9(34) orthogonal test. The pharmacological evaluation included in vitro tumor inhibition experiments and the survival extension rate in tumor-bearing nude mice. The fingerprint analyzed by chromatographic condition I (high-performance liquid chromatography-photodiode array detec tor，HPLC-PDA) identified 19 common peaks. High-performance liquid chromatography-photodiode array detector-Evaporative Light-scattering Detector (HPLC-PDA-ELSD )hyphenated techniques were used to compensate for the use of a single detector, and the fingerprint analyzed by chromatographic condition II identified 28 common peaks in PDA and 23 common peaks in ELSD. Furthermore, multiple statistical analyses were utilized to calculate the relationships between the peaks and the pharmacological results. The union of the regression and the correlation analysis results were the peaks of X5, X9, X11, X12, X16, X18, Y5, Y8, Y12, Y14, Y20, Z4, Z5, Z6, and Z8. The intersection of the regression and the correlation analysis results were the peaks of X11, X12, X16, X18, Y5, Y12, and Z5. The correlated peaks were assigned by comparing the fingerprints with the negative control samples and reference standard samples, and identifying the structure using high-performance liquid chromatography-mass spectrometry detector(HPLC-MS). The results suggested that the pharmacodynamic basis of LCSSY on anti-ovarian cancer activities were germacrone, furandiene, ß-elemene, calycosin-7-glucoside, ononin, epimedin B, icariin, ginsenoside Rc, astragaloside, ginsenoside Rd, astragaloside II, and some unknown components.

Effect of intense pulsed light on the expression of aquaporin 3 in rat skin.

Intense pulsed light (IPL) technology has been popularly employed in clinical treatments for dermatological and cosmetic purposes in recent years; yet, the underlying mechanisms of its functions are not fully elucidated. On the other hand, aquaporin (AQP) 3, a member of a subgroup of the aquaporin family that transports both water and small solutes, such as glycerol, has been documented to play an important role in the skin homeostasis. We thus examined the possible involvement of AQP3 in the functional mechanisms of IPL irradiation. Rat dorsal skin areas were irradiated one to three times with IPL at doses of 15, 25, and 35 J/cm2. Skin specimens were collected 7 days after the final irradiation and analyzed for changes in histology, skin hydration, mRNA, and protein expressions of AQP3. IPL induced no significant variations in the mRNA expression levels. Twice or thrice irradiation at the dose of 25 or 35 J/cm2 significantly enhanced AQP3 protein expression. Immunofluorescence study revealed that AQP3 was mainly localized to keratinocyte membranes in the basal layer of epidermis, and the localization was unaltered by IPL. In addition, the pattern of IPL-induced changes in skin hydration was generally coincided with the expression profile of AQP3. These results suggest the possibility that one of the functional mechanisms of IPL might be related to the regulation of AQP3 protein expression.

Emulsifiable oil-formulated Beauveria bassiana competes with imidacloprid for seasonal control of cereal aphids in Zhejiang, China.

BACKGROUND: Alternatives to neonicotinoids against cereal aphids are needed to mitigate aphid resistance and non-target effects. The emulsifiable oil formulations of two Beauveria bassiana strains, namely Bb registered as a mycoinsecticide and TBb overexpressing an endogenous virulence factor, were tested for seasonal control of cereal aphids at the elongating (April 7) to milk ripening (May 12) stages of winter wheat crop in Yuhang, Zhejiang. Each of three field trials consisted of blank control and the treatments (three randomized 100-m2 plots per capita) of each fungal strain sprayed biweekly at rates of 1.0 × 1013 and 1.5 × 1013 conidia ha-1 and 10% imidacloprid WP sprayed biweekly at a label rate. RESULTS: Tiller infestation percentage and aphid density in the 5-week field trials after the first spray were reduced to 18.7-22.4% and 9.1-12.4 aphids per tiller in the fungal treatments, and 12.8-25.3% and 2.8-20.9 aphids per tiller in the chemical treatment, contrasting with 49.2-60.3% and 37.1-108.5 aphids per tiller in the control. Percent control efficacies (±SD) computed with weekly aphid densities over the period averaged 84.0 ± 1.6 and 85.3 ± 1.8 versus 78.0 ± 4.0 and 79.9 ± 3.2 in the high-rate versus low-rate treatments of Bb and TBb, respectively, and 84.5 ± 7.8 in the chemical treatment. Imidacloprid showed faster kill action but more variable efficacy than the fungal treatments throughout the trials. CONCLUSION: Either Bb or TBb formulation competes with imidacloprid in reducing percent infestation and aphid density. The overall efficacy was significantly higher in the treatments of TBb than of Bb. © 2024 Society of Chemical Industry.

A landscape of methodology and implementation of adaptive designs in cancer clinical trials.

BACKGROUND: The use of adaptive designs in cancer trials has considerably increased worldwide in recent years, along with the release of various guidelines for their application. This systematic review aims to comprehensively summarize the key methodological and executive features of adaptive designs in cancer clinical trials. METHODS: A comprehensive search from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials was conducted to screen eligible clinical trials that employed adaptive designs and were conducted in cancer patients. The methodological and executive characteristics of adaptive designs were the main measurements extracted. Descriptive analyses, primarily consisting of frequency and percentage, were employed to analyzed and reported the data. RESULTS: A total of 180 cancer clinical trials with adaptive designs were identified. The first three most common type of adaptive design was the group sequential design (n=114, 63.3 %), adaptive dose-finding design (n=22, 12.2 %), and adaptive platform design (n=16, 8.9 %). The results showed that 4.4 % (n=8) of trials conducted post hoc modifications, and around 29.4 % (n=53) did not provide the methods for controlling type I errors. Among phase II or above trials, 79.9 % (112/140) applied the surrogate endpoint as the primary outcome in these trials. Importantly, 27.2 % (49/180) of trials did not report clear information on the independent data monitoring committee (iDMC), and 13.3 % (n=24) without clear information on interim analyses. Interim analyses suggested 34.4 % (62/180) of trials being stopped for futility, 10.6 % (n=19) for efficacy, and 2.2 % (n=4) for safety concerns in the early stage. CONCLUSIONS: This study emphasizes adaptive designs in cancer trials face significant challenges in their design or strict implementation according to protocol, which might significantly compromise the validity and integrity of trials. It is thus important for researchers, sponsors, and policymakers to actively oversee and guide their application.

Development of a tetra-primer ARMS-PCR for identification of sika and red deer and their hybrids.

Accurate identification of deer-derived components is significant in food and drug authenticity. Over the years, several methods have been developed to authenticate these products; however, identifying whether female deer products are hybrids is challenging. In this study, the zinc finger protein X-linked (ZFX) gene sequences of sika deer (Cervus nippon), red deer (Cervus elaphus) and their hybrid offspring were amplified and sequenced, the X221 and X428 species-specific single nucleotide polymorphisms (SNP) loci were verified, and a tetra-primer amplification refractory mutation system (T-ARMS-PCR) assay was developed to identify the parent-of-origin of female sika deer, red deer, and their hybrid deer. The T-ARMS-PCR developed based on the X221 locus could identify sika deer, red deer, and their hybrid offspring according to the presence or absence of PCR product sizes of 486 bp, 352 bp, and 179 bp, respectively, just as X428 locus could identify sika deer, red deer, and their hybrid offspring according to the presence or absence of PCR product sizes of 549 bp, 213 bp, and 383 bp, respectively. Forty products labeled deer-derived ingredients randomly purchased were tested using this assay, and the results showed that the identification results based on the two SNP loci were utterly consistent with the actual sources. In addition, this method was found to be accurate, simple, convenient, and with high specificity, thus providing an essential technical reference for deer product species identification. It is also an important supplement to the identification methods of the original ingredients of existing deer products.

Expression of aquaporins in rat liver regeneration.

OBJECTIVE: The remarkable ability of liver to regenerate after insults has been harnessed by surgeons when designing techniques for liver resection or transplantation. However, the underlying mechanisms of liver regeneration are not fully clarified. On the other hand, aquaporins (AQPs) are small transmembrane proteins with unexpected physiological roles in addition to water transport. For example, they play pivotal roles in cell migration, angiogenesis, and cell proliferation, events that are also occurred during liver regeneration. We thus examined the possible involvement of AQPs in this regenerative process. MATERIAL AND METHODS: A two-thirds partial hepatectomy (PH) rat model was employed. The temporal expression of various AQPs in the liver following PH was determined by semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. The localization of AQPs was evaluated by immunohistochemistry. RESULTS: As anticipated, AQP0, 8, 9, and 11 were detected mainly in hepatocytes; unexpectedly, Kupffer cells were observed to express AQP8 during a specific period of time in the regenerative process. AQP9 protein was shown to be expressed in a progressively enhanced pattern at early time points after PH. A transient expression of AQP11 in the nucleus of hepatocytes was observed. CONCLUSION: These findings suggest the possibility that AQP might be involved in the PH-induced liver regeneration.

Effect of docosahexaenoic acid on hypoxia/reoxygenation injury in human coronary arterial smooth muscle cells.

PURPOSE: Hypoxia and reoxygenation (H/R) occur in a wide variety of important clinical conditions such as myocardial infarction. H/R injury is a complex phenomenon involving not only intracellular damage processes but also an injurious inflammatory response. Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, has long been proved to be protective against several types of cardiovascular disease. However, its beneficial effect during H/R is inconclusive. In this study, we employed an in vitro model to examine whether DHA is protective against H/R-induced cell damage in human coronary artery smooth muscle cells (HCASMCs). METHODS: HCASMCs in the absence or presence of DHA (1, 3, 10, and 30 µM) were subjected to control or H/R treatment using a modular incubator chamber to create hypoxic condition. Cell viability was evaluated by MTT assay. Spectrophotometric and spectrofluorometric assays were used to measure the generation of nitric oxide (NO) and reactive oxygen species (ROS), respectively. Inflammatory cytokines were determined by enzyme-linked immunosorbent assay. Intracellular calcium mobilization was estimated microfluorimetrically using calcium indicator dye, fura 2-acetomethyl ester. RESULTS: Hypoxia/reoxygenation caused significant injury in cultured HCASMCs. DHA at low concentrations (1, 3, and 10 µM) did not afford protection, whereas at 30 µM, it caused deleterious effects, presumably by enhancing the production of NO, ROS, IL-1ß, and IL-6 and altering the intracellular calcium dynamics. CONCLUSIONS: Our results do not support the protective function of DHA in H/R-injured coronary arterial smooth muscle cells.

Modulating and driving system for the application of microelectromechanical system infrared source array.

A problem demanding to be solved in the development of microelectromechanical system (MEMS) IR source array has been the driving circuit and system. A method that can achieve the requirements of high driving power, high output efficiency, high voltage precision, voltage compensation, and deep frequency modulation for driving and modulating a MEMS IR source array was proposed. A liner DC steady voltage integrated circuit ADP3336 is used to drive the source array directly with a programmable compensation module ensuring the precision of radiation peak wavelength. And a FPGA as the control core of the system modulates the frequency and width of the driving pulse to control the array coding pattern. The engineering value of the system would be increased with the application of the MEMS IR source.

Which Is Safer, Chinese Medicine or Western Medicine? Comparative Analysis Based on Chinese Spontaneous Reporting Database.

OBJECTIVE: To compare the safety differences between Chinese medicine (CM) and Western medicine (WM) based on Chinese Spontaneous Reporting Database (CSRD). METHODS: Reports of adverse events (AEs) caused by CM and WM in the CSRD between 2010 and 2011 were selected. The following assessment indicators were constructed: the proportion of serious AEs (PSE), the average number of AEs (ANA), and the coverage rate of AEs (CRA). Further comparisons were also conducted, including the drugs with the most reported serious AEs, the AEs with the biggest report number, and the 5 serious AEs of interest (including death, anaphylactic shock, coma, dyspnea and abnormal liver function). RESULTS: The PSE, ANA and CRA of WM were 1.09, 8.23 and 2.35 times higher than those of CM, respectively. The top 10 drugs with the most serious AEs were mainly injections for CM and antibiotics for WM. The AEs with the most reports were rash, pruritus, nausea, dizziness and vomiting for both CM and WM. The proportions of CM and WM in anaphylactic shock and coma were similar. For abnormal liver function and death, the proportions of WM were 5.47 and 3.00 times higher than those of CM, respectively. CONCLUSION: Based on CSRD, CM was safer than WM at the average level from the perspective of adverse drug reactions.

Erratum: Jiedu Sangen Decoction Reverses Epithelial-to-mesenchymal Transition and Inhibits Invasion and Metastasis of Colon Cancer via AKT/GSK-3ß Signaling Pathway: Erratum.

[This corrects the article DOI: 10.7150/jca.32873.].

Self-Organization Formation of Multicellular Spheroids Mediated by Mechanically Tunable Hydrogel Platform: Toward Revealing the Synergy of Chemo- and Noninvasive Photothermal Therapy against Colon Microtumor.

Three-dimensional (3D) tumor cell culture offers a more tissue-recapitulating model in cancer treatment evaluation. However, conventional models based on cell-substrate adhesion deprivation are still of insufficient real tumor mimic. In this work, a novel method is proposed for inducing multicellular spheroids (MCSs) formation based on hydrogel with tunable microenvironmental properties. Colon tumor cells DLD1 cultured on hydrogel substrate with proper physical stimulation form MCSs via self-organization. Chemotherapy based on clinical drug and far-infrared photothermal therapy is evaluated with DLD1 MCSs obtained by this method. The synergism of chemotherapy and noninvasive photothermal therapy based on graphene device is further verified in MCSs model and it is believed this method holds potential in in vitro anti-tumor strategies evaluation for precision medicine.

Mutation Analysis of the RPGR Gene in a Chinese Cohort.

Purpose: The purpose of this study was to investigate the clinical and genetic characteristics of the retinitis pigmentosa GTPase regulatory factor gene (RPGR) in a Chinese cohort. Methods: A retrospective analysis was performed on 80 subjects with RPGR-retinal dystrophy (RPGR-RD) for detailed genetic and clinical characterization. The panel-based next-generation sequencing of 792 causative genes involved in common genetic eye diseases was conducted in all individuals, followed by clinical variant interpretation. Information, including age, sex, geographic distribution, family history, consanguineous marriage, age at symptom onset, disease duration, best corrected visual acuity (BCVA), and complete ophthalmologic examination results, was collected. Results: This cohort (41 men and 39 women) included 26 families (26 probands and their available family members) and 13 sporadic cases. The average age of these participants was 36.35 ± 17.68 years, and the majority of the families were from eastern China (28 families, 71.79%). The average duration of disease in the probands was 22.68 ± 15.80 years. In addition, the average BCVA values of the right and left eyes in the probands were 0.96 ± 0.77 and 1.00 ± 0.77, respectively. A total of 34 RPGR variants were identified, including 6 reported variants and 28 novel variants. Among these variants, NM_001034853.1: c.2899_2902delGAAG and c.2744_2745ins24 were considered de novo variants. The majority of the RPGR variants were classified as likely pathogenic, accounting for 70.59% of the variants (24 variants). The most common nucleotide and amino acid changes identified in this study were deletions (16 variants, 45.06%) and frameshifts (17 variants, 50.00%), respectively. Genetic analysis revealed that these RPGR variants were distributed in 10 different subregions of RPGR, and 70.59% of the RPGR variants (24 variants) were located in exon 15. Four RPGR variants, NM_001034853.1: c.2405_2406delAG, c.1345C > T, c.2218G > T and c.2236_2237delGA, occurred at a very high frequency of 28.21% (11 families) among 39 unrelated families. Conclusion: This study expands the known mutational spectrum of RPGR, and we provide a new reference for the genetic diagnosis of RPGR variants.

The prognostic value of 4.1 mRNA expression in non-small cell lung cancer.

BACKGROUND: The mechanism of 4.1 family in human cancer has not been elucidated. In this study we investigate the value as a prognostic factor of mRNA expression of 4.1 family in non-small cell lung cancer (NSCLC). METHODS: A survival analysis was carried out through the Kaplan-Meier plotter (KM plotter) database. KM's method was used to estimate the prognostic value of 4.1 mRNA expression in NSCLC. RESULTS: Expression of four members are linked to overall survival (OS) in NSCLC patients, among which 4.1G, 4.1B, 4.1R are concerned with first progression (FP), and 4.1G, 4.1R are correlated with post progression survival (PPS) besides. Only 4.1B expression is associated with OS in squamous cell carcinoma, as four members with OS in adenocarcinoma. What's more, 4.1G, 4.1N high mRNA are linked to better FP in adenocarcinoma, and 4.1R overexpression is linked to better PPS. The expression of 4.1G is associated with the prognosis in female, whereas 4.1R in male. Furthermore, 4.1G and 4.1B play as protective roles in non-smoking populations, while 4.1N overexpression is related to poorer PPS. All the four family members are associated with early stage in NSCLC 4.1G, 4.1B and 4.1R are closely related to surgical resection, yet 4.1N has no prognostic significance in patients receiving treatments. However, the results need to be verified in clinical trials further. CONCLUSIONS: Our results offer new opinion about the prognostic value of 4.1 protein family in NSCLC, which may contribute to the development of new therapy for NSCLC.