Association of serum 25-hydroxyvitamin D with cardiovascular mortality and kidney outcome in patients with early stages of CKD.

PURPOSE: While serum 25-hydroxyvitamin D (25[OH]D) deficiency is prevalent in chronic kidney disease (CKD), the effects of 25(OH)D deficiency on cardiovascular mortality and kidney outcomes in patients with early-stage CKD remain incompletely understood. METHODS: This multicenter retrospective cohort study included adult patients with stages 1-3 CKD from 19 medical centers across China between January 2000 and May 2021. The primary outcome was cardiovascular mortality. The secondary study outcome included CKD progression (defined as a sustained > 40% eGFR decrease from baseline or progress to end-stage kidney disease), and annual percentage change of eGFR. RESULTS: Of 9229 adults with stages 1-3 CKD, 27.0% and 38.9% had severe (< 10 ng/mL) and moderate (10 to < 20 ng/mL) serum 25(OH)D deficiency, respectively. Compared with patients having 25(OH)D ≥ 20 ng/mL, a significantly higher risk of cardiovascular mortality (hazard ratio [HR] 1.90, 95% CI 1.37-2.63), CKD progression (HR 2.20, 95% CI 1.68-2.88), and a steeper annual decline in eGFR (estimate - 7.87%; 95% CI - 10.24% to - 5.51% per year) was found in those with serum 25(OH)D < 10 ng/mL. Similar results were obtained in subgroups and by sensitivity analyses. CONCLUSIONS: 25(OH)D deficiency is associated with increased risks of cardiovascular mortality and CKD progression in patients with early-stage CKD. Studies are needed to determine whether early intervention for 25(OH)D deficiency could improve the prognosis of patients with early-stage CKD.

[EQ-5D-3L based quality of life for patients of pneumoconiosis combined with tuberculosis and its influencing factors].

Objective: To understand the health-related quality of life for patients of pneumoconiosis combined with tuberculosis and its main influencing factors. Methods: This was a cross-sectional study, and 951 patients of pneumoconiosis combined with tuberculosis from the pneumoconiosis survey in 27 provinces and autonomous regions in China from December 2017 to December 2021 were selected for the study. The nonparametric Mann-Whitney test and the Kruskal-Wallis H test were used to compare the health utility values, and multiple linear regression was used for multifactor analysis. AMOS 24.0 was used to establish a structural equation modeling. Results: The mean age of 951 patients of pneumoconiosis combined with tuberculosis was (59.3±12.4) years. The main types were silicosis combined with tuberculosis (62.2%, 591/951) and coal-worker's pneumoconiosis combined with tuberculosis (34.9%, 332/951), and other type pneumoconiosis-combined tuberculosis was 2.9% (28/951). The proportion of patients with stage Ⅰ, Ⅱ, Ⅲ, and unstaged clinical diagnosis was 27.4% (261/951), 26.6% (253/951), 32.5% (309/951) and 13.5% (128/951), respectively. 63.3% (602/951) of study participants suffered from other chronic diseases, and the percentage of patients combined the number of chronic diseases with 1, 2, and more than 3 respectively were 24.1% (229/951), 16.3% (155/951) and 22.9% (218/951). The median and quartiles of health utility values and the mean±standard deviation of self-rating scores of patients of pneumoconiosis combined with tuberculosis were 0.562 (0.482, 0.766) and (53.7±18.4), respectively, which were lower than patients of pneumoconiosis without tuberculosis (Z=-11.29, P<0.001; t=8.97, P<0.01). The health utility values and self-rating scores for patients of pneumoconiosis combined with tuberculosis were significantly different between urban and rural areas (Z= -2.22, P=0.027; t=4.85, P<0.01). Pain/discomfort was the most frequently reported problem in the five-dimensional distribution of problems, followed by daily activities and anxiety/depression, and the difference in the percentage reported by anxiety/depression between urban and rural areas was significant (χ(2)=30.28, P<0.01). The results of multiple linear regression showed that the survey area, body mass index, education level, age, employment status, annual personal income, stage of pneumoconiosis, number of multi-morbidities, hemoptysis, acute exacerbation of symptoms in two-week, social support and minimum living standard were the main influences on the health utility values of the patients of pneumoconiosis combined with tuberculosis (P<0.05). The results of structural equation model showed that economic security and health status directly affected the health-related quality of life among patients of pneumoconiosis combined with tuberculosis and played a chain-mediating effect in the influence of socioeconomic status on the health-related quality of life among patients of pneumoconiosis combined with tuberculosis. Conclusion: Health-related quality of life was poorer in patients of pneumoconiosis with tuberculosis, with pain and discomfort and anxiety/depression problems being more pronounced, and economic status and health status played multiple mediating roles in the influence of general socio-demographic characteristics on quality of life in pneumoconiosis.

[Clinical characteristics and therapeutic effectiveness of post craniotomy cervicogenic headache].

From January 2019 to December 2021, the clinical data of 151 patients with post craniotomy cervicogenic headache from Beijing Tiantan Hospital affiliated to Capital Medical University were retrospectively collected. The characteristics of cervicogenic headache were summarized, the numerical rating score (NRS) of patients before and after treatment of compound opioids and/or cervical nerve block was compared, and the occurrence of related adverse reactions and complications was counted. The onset of cervicogenic headache in 151 patients was on the (5.5±2.0) d after craniotomy, of which 131 (86.8%) had unilateral pain, pain in 127 (84.1%) could be induced by cervical activity, and 118 (78.1%) had limited neck movement. Of the 124 patients treated with compound capsule of oxycodone and acetaminophen, 85 (68.5%) patients had an NRS of (8.01±0.82) before treatment and 2.0 (1.0, 3.0) after treatment (P<0.001). Thirty-nine patients who did not respond to medical therapy received cervical nerve block, and the NRS scores before and after receiving the nerve block were (7.49±1.12) and 2.0 (1.0, 2.5), respectively, with a statistically significant difference (P<0.001). Twenty-seven patients who received cervical nerve block without medical treatment, and the NRS before and after treatment was (9.0±0.9) and 1.0 (1.0, 3.0), respectively, with a statistically significant difference (P<0.001). Among the 124 patients receiving medication, 14 (11.3%) developed mild dizziness and nausea, which were resolved after stopping the drug, and no other drug-related adverse reactions were found. None of the patients who received nerve blocks saw complications associated with nerve block procedures. Compound capsule of oxycodone and acetaminophen are effective for most of patients with post craniotomy cervicogenic headache. Cervical nerve block is effective and safe for patients with or without drug resistance.

[Correlation between fluid parameter and cardiovascular events in hemodialysis patients based on repeated body composition analyses].

Objective: To explore the correlation between fluid load index and cardiovascular events in hemodialysis patients based on repeated body composition analyses. Methods: A prospective cohort study was conducted to collect the clinical data of patients undergoing maintenance hemodialysis (MHD) in the Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine from July to September 2020. The pre-dialysis fluid overload (FO) index-overhydration (OH) was measured by bioelectrical impedance method, and the follow-up monitoring was conducted every 6 months. According to the baseline OH value, patients were divided into non-FO group (OH≤2.5 L) and FO group (OH>2.5 L). Moreover, according to the repeated measurements, the patients were divided into continuous non-FO group, continuous FO group and intermittent FO group. All patients were followed up until October 1, 2022, and the outcomes were recorded. The end point of follow-up was cardiovascular events. The cumulative incidence of cardiovascular events was calculated by the Kaplan-Meier method, and the risk factors of cardiovascular events were analyzed by Cox proportional hazards regression model. Results: A total of 289 patients were included, including 88 patients (30.4%) with FO and 201 patients (69.6%) with non-FO. There were 168 males (58.1%) and 121 (41.9%) females, with an average age of (58±13) years and an average follow-up time of (22.0±6.5) months. Kaplan-Meier analysis showed that the incidence of cardiovascular events in the baseline FO group was higher than that in the non-FO group (log-rank χ2=14.44, P<0.001). The incidence of cardiovascular events in both the continuous FO group and the intermittent FO group was higher than that in the continuous non-FO group (log-rank χ2=41.47, P<0.001; log-rank χ2=18.36, P<0.001). After adjustment for gender, age, comorbidities, and biochemical indicators, the incidence of cardiovascular events in the baseline FO group was 1.850 times of the non-FO group (95%CI: 1.046-3.271, P=0.034). The incidence of cardiovascular events in the continuous FO group was 4.679 times of the continuous non-FO group (95%CI: 2.189-10.002, P<0.001). The incidence of cardiovascular events in the intermittent FO group was 3.410 times of the continuous non-FO group (95%CI: 1.696-6.857, P=0.001). Conclusions: OH value measured by bioelectrical impedance can be used as an important reference index for clinical monitoring of cardiovascular events in MHD patients. Continuous chronic and intermittent exposures to FO are risk factors for cardiovascular events in hemodialysis patients.

Biopsy-tract haemocoagulase injection reduces major complications after CT-guided percutaneous transthoracic lung biopsy.

AIM: To determine whether the injection of haemocoagulase into the biopsy tract can reduce pneumothorax and pulmonary haemorrhage after computed tomography (CT)-guided percutaneous transthoracic lung biopsy (PTLB). MATERIALS AND METHODS: A retrospective study was performed involving patients with undiagnosed pulmonary lesions scheduled for PTLB between January 2020 and March 2021. Patients were assigned to the haemocoagulase group or the non-haemocoagulase group. After CT-guided biopsies were performed with a 17 G coaxial system, patients in the haemocoagulase group received a haemocoagulase injection (0.2-0.5 units) in the biopsy tract as the sheath was withdrawn. Postoperative image studies were performed to evaluate complications, including pneumothorax and pulmonary haemorrhage. Factors, including the patient's position, lesion location, and pathological results, were evaluated to determine their associations with the complications. RESULTS: A total of 100 patients were included, with 44 men and a mean age of 53 years old. The overall incidences of pneumothorax and pulmonary haemorrhage were 15% and 13%, respectively. The incidences of pneumothorax and pulmonary haemorrhage were statistically significantly lower in the haemocoagulase group (8% and 6%, respectively) than in the non-haemocoagulase group (22% and 20%, respectively; p=0.04 and 0.03, respectively). There was no statistically significant difference in haemoptysis between the haemocoagulase (6%) and non-haemocoagulase (2%) groups (p=0.23). There were also no statistically significant associations of pneumothorax or pulmonary haemorrhage with the patients' positions, lesion location, or pathological results. CONCLUSION: Biopsy tract haemocoagulase injection reduced the incidences of postoperative pneumothorax and pulmonary haemorrhage after PTLB.

Combined and interactive effects of alcohol drinking and cigarette smoking on the risk of severe illness and poor clinical outcomes in patients with COVID-19: a multicentre retrospective cohort study.

OBJECTIVES: Cigarette smoking is an established risk factor for illness severity and adverse outcomes in patients with COVID-19. Alcohol drinking may also be a potential risk factor for disease severity. However, the combined and interactive effects of drinking and smoking on COVID-19 have not yet been reported. This study aimed to examine the combined and interactive effects of alcohol drinking and cigarette smoking on the risk of severe illness and poor outcomes in patients with COVID-19. STUDY DESIGN: This was a multicentre retrospective cohort study. METHODS: This study retrospectively reviewed the data of 1399 consecutive hospitalised COVID-19 patients from 43 designated hospitals. Patients were grouped according to different combinations of drinking and smoking status. Multivariate mixed-effects logistic regression models were used to estimate the combined and interactive effects of drinking and smoking on the risk of severe COVID-19 and poor clinical outcomes. RESULTS: In the study population, 7.3% were drinkers/smokers, 4.3% were drinkers/non-smokers and 4.9% were non-drinkers/smokers. After controlling for potential confounders, smokers or drinkers alone did not show a significant increase in the risk of severe COVID-19 or poor clinical outcomes compared with non-drinkers/non-smokers. Moreover, this study did not observe any interactive effects of drinking and smoking on COVID-19. Drinkers/smokers had a 62% increased risk (odds ratio = 1.62, 95% confidence interval: 1.01-2.60) of severe COVID-19 but did not have a significant increase in the risk for poor clinical outcomes compared with non-drinkers/non-smokers. CONCLUSIONS: Combined exposure to drinking and smoking increases the risk of severe COVID-19, but no direct effects of drinking or smoking, or interaction effects of drinking and smoking, were detected.

[The effect of visualized saphenous nerve block through minimally invasive far medial-subvastus approach on the analgesia after total knee arthroplasty].

Objective: To report a method of visualized saphenous nerve block (VSNB) through minimally invasive far medial-subvastus approach distal to the adductor canal in total knee arthroplasty (TKA), and investigate the effect of VSNB in this way on postoperative pain relief. Methods: A total of 100 patients with knee osteoarthritis were prospectively included from June 2018 to October 2019, 29 males and 71 females, aged 50-87(70±8) years. All patients undergoing TKA through minimally invasive far medial-subvastus approach were randomized to visualized saphenous nerve block combined with periarticular infiltration analgesia group (Group VSNB+PIA) or only periarticular infiltration analgesia group (Group PIA),50 cases in each group. The visual analogue scale (VAS) was used to evaluate the pain degree of patients. Furthermore, the scores of VAS in resting and active state at 4, 8, 12, 24, 48, 72 hours after operation and the proportion of patients receiving parecoxib within 72 hours after operation were compared between the two groups. Results: There was statistically significant difference between the two groups in terms of VAS scores in resting state after surgery(F=15.295,P<0.05).The postoperative VAS scores of Group VSNB+PIA at 4, 8, 12, 24 hours at resting state were 1.3±0.8, 1.4±0.7, 1.7±0.8, 3.1±0.8 respectively, which were all significantly lower than those of Group PIA (1.6±0.9, 1.8±0.8, 2.3±0.9, 3.6±0.8) (P<0.05). The overall difference in terms of VAS scores at active state after surgery was statistically significant between the two groups(F=18.532, P<0.05). The postoperative VAS scores of Group VSNB+PIA at 4, 8, 12, 24 hours at active state were 2.0±0.8, 2.2±0.7, 2.7±0.6, 3.7±0.7 respectively, which were all significantly lower than those of Group PIA (2.3±0.8, 2.7±0.7, 3.3±0.8, 4.4±0.7)(P<0.05). Fourteen percent of patients (7/50) in VSNB+PIA group accepted parecoxib within 72 hours after surgery, which was significantly lower than that in PIA group (34%, 17/50) (P<0.05). Conclusions: It is easy to expose the saphenous nerve beyond the adductor canal through minimally invasive far medial-subvastus approach. The Combination therapy of VSNB+PIA is more effective than the simple per-articular infiltration analgesia in providing pain relief after total knee arthroplasty.

[Short-term efficacy of endoscope assisted arthroplasty for total hip replacement via a minimum invasive direct anterior approach].

Objective: To present the surgical technique of endoscope assisted arthroplasty for total hip replacement via minimum invasive direct anterior approach and analyze its early clinical outcome. Methods: From November 2019 to May 2020, endoscopic total hip arthroplasty via direct anterior approach was performed on 30 patients (32 hips), including 12 males (13 hips) and 18 females (19hips), in the Department of Orthopedics of Fujian Provincial Hospital. The average age of patients was (63±14) years (ranged 32-87 years). The average body mass index (BMI) of the patients was (26.9±4.5) kg/m2. There were 12 cases whose BMI was higher than 28.0 kg/m2 and the maximum BMI was 35.2 kg/m2. The surgery was performed on supine position using a 5-6 cm proximal transverse incision and a distal selective percutaneous puncture incision to perform the acetabulum preparation and the prosthesis implantation with the novel designed split tool under the monitoring of endoscope; the lift-top tractor system was used to raise the femur in the transverse incision for femoral side preparation and prosthesis implantation. Relevant data such as the perioperative status, operation time, postoperative pain score assessed with visual analogue score (VAS), prosthesis position, joint function, lateral femoral cutaneous nerve function and patient satisfaction were recorded to analyze the short-term efficacy. Results: The average length of incision of the 30 cases(32 hips)was (5.9±0.4) cm. All patients in this study had I/A wound healing with no perioperative complications such as infection, poor wound healing and fractures of the proximal femur. The average operation time was (65±14) min, and the average amount of blood loss was (136±56) ml. The average acetabular abduction angle and acetabular antegrade inclinations was 41.4°±3.6° and 16.0°±5.3°, respectively. The resting-state VAS of pain at 6 h and 24 h after operation were all ≤2, and there was no significant difference between the VAS scores after exercise and the VAS scores at the resting state (both P>0.05). There was no statistically significant difference between the VAS scores at the same state at different times (both>0.05). The weight-bearing exercise was applied in all patients within 12 h after surgery. The length of postoperative hospital stays varied from 1 to 3 days((2.0±0.9) days). At the 6th-month follow-up, the Harris score of the hip was 94.7±3.0, which significantly improved when compared with that before the operation (35.5±8.1)(P<0.01). No sensory abnormalities were observed. The satisfaction score of the patients was 9.3±0.5 (full score set to 10). Conclusions: The efficacy and safety of the endoscope assisted total hip arthroplasty for total hip replacement is acceptable. This procedure can help to reduce the compression of the muscles by the retractor in the conventional operation. It can be applied to obese and muscular patients.

[Correlational verification of drug-induced liver injury with HLA-B*35:01 allele due to Polygonum multiflorum].

In order to verify the correlation between Polygonum multiflorum-induced liver injury and HLA-B*35 : 01 alleles, six hospitalized patients diagnosed with Polygonum multiflorum-induced liver injury (PM-DILI) were selected, and their clinicopathological data were collected. Simultaneously, blood HLA-B* 35 : 01 allele detection was performed. Among the six PM-DILI cases, 4 were male, aged 38.83 ± 10.13 years old. The types of liver injury were hepatocellular injury types in all, and the severity of liver injury in five cases was grade 3. The histological presentations were acute hepatitis and acute cholestatic hepatitis. PM-DILI cases were all HLA-B*35:01 carriers, with a carrier rate of 100%. This finding indicates that PM-DILI is significantly correlated with HLA-B*35:01 alleles. Therefore, HLA-B*35 : 01 alleles can be used as an important predictive indicator for PM-DILI.

Safety and Efficacy of Aspirin Desensitization Combined With Long-Term Aspirin Therapy in Aspirin-Exacerbated Respiratory Disease.

OBJECTIVES: To assess the safety and efficacy of Aspirin desensitization combined with long-term Aspirin therapy in patients with Aspirinexacerbated respiratory disease (AERD). METHODS: We searched the PubMed, Ovid, Cochrane Library, and Google Scholar databases from inception to October 2018 for articles in English. We only included randomized controlled trials and parallel or cross-over studies in which adults with AERD were randomly assigned to undergo Aspirin desensitization and receive long-term Aspirin therapy or placebo. RESULTS: A total of 869 citations were retrieved, and 6 studies met the criteria for analysis. All studies indicated that nasal symptoms, asthma symptoms, or both improved significantly after Aspirin desensitization. In addition, most studies reported a decline in corticosteroid dosage (oral and inhaled). The 4 studies that reported nasal polyps did not demonstrate a change in nasal polyps with Aspirin therapy compared with placebo. The dropout rates in all studies reviewed ranged from 5.8% to 55.7%, and the most common adverse events were gastrointestinal symptoms. CONCLUSIONS: Clearly, Aspirin desensitization and treatment are beneficial for AERD patients, with relief of nasal symptoms, improvement in asthma control, decrease in daily corticosteroid use, and no fatal adverse events. However, the long-term adverse effects of Aspirin desensitization and optimal dosage of Aspirin merit further investigation.

MicroRNA-370-3p inhibits cell proliferation and induces chronic myelogenous leukaemia cell apoptosis by suppressing PDLIM1/Wnt/ß-catenin signaling.

Growing evidence has suggested that microRNA-370-3p (miR-370-3p) is downregulated and acts as a suppressor in several cancers. However, the role of miR-370-3p in chronic myeloid leukemia (CML) remains unknown. Here, the expression level and molecular mechanism of miR-370-3p in CML were investigated. Firstly, the expression of miR-370-3p has markedly decreased in the peripheral blood mononuclear cells (PBMCs) of patients with CML and in cell lines. Moreover, miR-370-3p in CML cells upregulated and downregulated proliferation and apoptosis, respectively. Notably, miR-370-3p directly targeted the 3'-untranslated region of PDZ and LIM domain protein 1 (PDLIM1). A negative correlation was observed between the levels of miR-370-3p and PDLIM1 in the PBMCs of patients with CML and healthy volunteers. PDLIM1 was shown to have an oncogenic role in CML cells by promoting proliferation and suppressing apoptosis. Finally, the miR-370-3p-PDLIM1-Wnt/ß-catenin signaling axis was indicated to play an important role in CML progression.

Study Frequency Shift Evaluation of Ultrasound in Fresh and Frozen-thawed Tissues of Cryosurgery by AR Model.

BACKGROUND: Noninvasive monitoring of cryosurgery is important for performing precise monitoring of the freezing process in situ and evaluating postoperative effects after therapy. One potential approach is to monitor the normal and freeze-thawed tissues through ultrasonic backscattered signal processing. OBJECTIVE: A noninvasive method for cryosurgery monitoring based on the analysis of microstructural characteristics of in vitro porcine liver tissues at different state including normal and freeze-thawed tissues by estimating the center frequency of scatterers (CFS) using the autoregressive (AR) cepstrum of ultrasonic backscattered signals. MATERIALS AND METHODS: The method is based on the discrete scattering model described in the tissue characterization literature and the observation that most biological tissues are semi-regular scattering lattices. A total of ten in vitro porcine liver samples were used and freeze by water bath in the experiments. RESULTS: Experimental results show that the CFS in porcine liver tissues decreases after pre-frozen and then thawed. CONCLUSION: The CFS obtained using this method may be used as a characteristic parameter for tissue characterization in noninvasive monitoring the transition zone between frozen and unfrozen tissues during the surgical therapy, and evaluating postoperative effects.

[Preliminary clinical analysis of direct renin inhibitor aliskiren in the treatment of severe coronavirus disease 2019 patients with hypertension].

Objective: To explore the feasibility of direct renin inhibitor aliskiren for the treatment of severe or critical coronavirus disease 2019 (COVID-19) patients with hypertension. Methods: The antihypertensive effects and safety of aliskiren was retrospectively analyzed in three severe and one critical COVID-19 patients with hypertension. Results: Four patients, two males and two females, with an average age of 78 years (66-87 years), were referred to hospital mainly because of respiratory symptoms. Three were diagnosed by positive novel coronavirus 2019 (2019-nCoV) nucleic acid or antibody, and the critical patient with cardiac insufficiency was clinically determined. Two patients were treated with calcium channel antagonist (CCB), one with angiotensin converting enzyme inhibitor (ACEI), and one with angiotensin Ⅱ receptor antagonist (ARB). After admission, ACEI and ARB were discontinued, one patient with heart failure was treated by aliskiren combined with diuretic.Three patients were treated with aliskiren combined with CCB among whom two withdrew CCB due to low blood pressure after 1 to 2 weeks. Based on comprehensive treatment including antiviral and oxygenation treatment, blood pressure was satisfactorily controlled by aliskiren after three to four weeks without serious adverse events. All patients were finally discharged. Conclusion: Our preliminary clinical data shows that antihypertensive effect of aliskiren is satisfactory and safe for severe COVID-19 patients complicated with hypertension.

[Common peroneal nerve "pre-release" to avoid nerve palsy in total knee arthroplasty for severe valgus deformities].

Objective: To investigate the clinical efficacy of common peroneal nerve "pre-release" to avoid nerve palsy in total knee arthroplasty for severe valgus deformities. Methods: Twenty patients (22 knees) with severe valgus deformities were prospectively and continuously included in Fujian Province Hospital from January 2010 to January 2016. Medial parapatellar arthrotomy, femoral distal resection using the intramedullary cutting guide with 3° to 5° of valgus and the common peroneal nerve "pre-release" was performed, the patella was routinely resurfaced. A common peroneal nerve checking was performed (LSUHSC system), then, these outcomes were collected independently using visual analogue scale (VAS) of pain, Knee Society Score (KSS), Hospital for Special Surgery Knee Score (HSS), range of motion of knees (ROM), femorotibial angle (FTA), hip-knee-ankle angle (HKA), condylar-hip angle (CHA), plateau- ankle angle (PAA). The paired t test was used to compare the data before and after the operation. Results: Patients were followed up for 18 to 55 (mean, (38±8) months). According to Krackow's classification, all cases were typed Ⅱ. All the patients had a completely normal motor (grade 5) and sensory (LSUHSC score was 5) nerve function of common peroneal nerve postoperatively. No decrease or loss in muscle strength and cutaneous sensation associated with common peroneal nerve was found. The VAS of pain, KSS, HSS, ROM, HKA, CHA, and PAA were all improved after the operation when compared with those before the operation (t=21.602, -70.238, -82.455, -20.560, 16.058, 9.682, 3.439, all P<0.05). The alignment of lower limbs was corrected basically, and the FTA decreased from 31.7°±8.0° before operation to 5.0°±2.0° at the last follow-up, the differences was statistically significant (t=16.725, P<0.05). No common peroneal nerve palsy and transient or late-onset palsy occurred, and no revision was needed for instability during the follow-up in all the patients. Conclusion: Common peroneal nerve "pre-release" for severe valgus knees may be an effective method in protecting the nerve.

Frequency Characteristics of AEPs in Normal Young Adults and Comparison of Their Response Threshold and Pure Tone Audiometry Threshold.

ABSTRACT: Objective The tests of three types of auditory evoked potentials （AEPs） were performed on normal young adults, to understand the frequency characteristics of different testing methods and the relationship between response threshold and pure tone audiometry threshold of different methods, and to discuss the forensic value of 3 types of AEPs to evaluate hearing function. Methods Twenty normal young adults were selected, their standard pure tone audiometry threshold, short-term pure tone audiometry threshold and the response threshold of 3 types of AEPs （tone burst-auditory brainstem response, 40 Hz auditory event-related potential and slow vertex response） at 0.5 kHz, 1.0 kHz, 2.0 kHz and 4.0 kHz were recorded. The relationship between the response threshold and standard pure tone audiometry threshold, short-term pure tone audiometry threshold of 3 types of AEPs at different frequencies as well as the differences between different types of AEPs were analyzed. Results The short-term pure tone audiometry threshold was higher than the standard pure tone audiometry threshold at each frequency. The response threshold and standard pure tone audiometry threshold of the 3 types of AEPs all had a certain correlation, and the response threshold of the 3 types of AEPs was higher than short-term pure tone audiometry threshold and standard pure tone audiometry threshold at each frequency. The differences in the differences between the response threshold and standard pure tone audiometry threshold of the 3 types of AEPs at different frequencies had statistical significance. Linear regression mathematical models were established to infer the standard pure tone audiometry threshold （hearing level） from response threshold （sound pressure level） of 3 types of AEPs of normal young adults. Conclusion When using response threshold of different types of AEPs to estimate pure tone audiometry threshold, conversion and correction are needed. Combined use of different types of AEPs could improve the accuracy of hearing function evaluation.

Clenbuterol reduces GABAergic transmission in prefrontal cortex layer 5/6 pyramidal neurons of juvenile rat via reducing action potentials firing frequency of GABAergic interneurons.

Beta-adrenoceptors (ß2 -ARs) have beneficial effects on prefrontal cortex (PFC) working memory, however, the cellular and molecular mechanisms are unclear yet. In this study, we probed the effect of ß2 -AR-selective agonist clenbuterol (Clen) on synaptic transmission in layer 5/6 pyramidal neurons of PFC. Bath application of Clen reduced spontaneous IPSC (sIPSC) frequency without effects on sEPSCs. Clen did not alter the frequency and amplitude of miniature IPSCs (mIPSCs), but exerted heterogeneous effects on evoked IPSCs (eIPSCs) recorded from PFC layer 5/6 pyramidal neurons. Clen decreased the firing rate of action potentials of fast-spiking GABAergic interneurons. Clen-induced hyperpolarization of fast-spiking GABAergic interneurons required potentiation of an inward rectifier K+ channels. Clen-induced hyperpolarization of fast-spiking interneurons was dependent on Gs protein rather than cAMP and protein kinase A. Our findings demonstrate that Clen (10 µM) enhances inward rectifier K+ channels via Gs protein to cause membrane hyperpolarization of fast-spiking GABAergic interneurons resulting in reduction of action potentials firing rate to reduce GABAergic transmission.

A novel FGFR1-binding peptide attenuates the degeneration of articular cartilage in adult mice.

OBJECTIVE: We previously reported that genetic ablation of (Fibroblast Growth Factors Receptors) FGFR1 in knee cartilage attenuates the degeneration of articular cartilage in adult mice, which suggests that FGFR1 is a potential targeting molecule for osteoarthritis (OA). Here, we identified R1-P1, an inhibitory peptide for FGFR1 and investigated its effect on the pathogenesis of OA in mice induced by destabilization of medial meniscus (DMM). DESIGN: Binding ability between R1-P1 and FGFR1 protein was evaluated by enzyme-linked immuno sorbent assay (ELISA) and molecular docking. Alterations in cartilage were evaluated histologically. The expression levels of molecules associated with articular cartilage homeostasis and FGFR1 signaling were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC). The chondrocyte apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay. RESULTS: R1-P1 had highly binding affinities to human FGFR1 protein, and efficiently inhibited extracellular signal-regulated kinase (ERK)1/2 pathway in mouse primary chondrocytes. In addition, R1-P1 attenuated the IL-1ß induced significant loss of proteoglycan in full-thickness cartilage tissue from human femur head. Moreover, this peptide can significantly restore the IL-1ß mediated loss of proteoglycan and type II collagen (Col II) and attenuate the expression of matrix metalloproteinase-13 (MMP13) in mouse primary chondrocytes. Finally, intra-articular injection of R1-P1 remarkably attenuated the loss of proteoglycan and the destruction of articular cartilage and decreased the expressions of extracellular matrix (ECM) degrading enzymes and apoptosis in articular chondrocytes of mice underwent DMM surgery. CONCLUSIONS: R1-P1, a novel inhibitory peptide for FGFR1, attenuates the degeneration of articular cartilage in adult mice, which is a potential leading molecule for the treatment of OA.

TMEM45B is a novel predictive biomarker for prostate cancer progression and metastasis.

It is urgently needed to explore the clinical relevance of TMEM45B expression and Prostate cancer(PCa), and determine the predictive significance of TMEM45B as a biomarker for PCa patients.Patient-derived xenograft (PDX) model of PCa with different metastatic potential (LTL-418, LTL-313B, LTL-313H and LTL-331) were developed. The gene expression microarray of LTL-313H and LTL-313B, which derived from a single PCa patient, was performed to identify the candidate biomarker gene, TMRM45B. MSKCC and TCGA PCa patient cohorts were introduced to analyzed the clinical significance of TMEM45B expression. Quantitative Real-Time PCR (qRT-PCR) revealed that there was a significant increase of TMEM45B expression in high metastatic potential tumor lines LTL-313H and LTL-331 compared with the other two low metastatic potential tumor lines(LTL-418, LTL-313B). In MSKCC PCa cohort, the mRNA level of TMEM45B in patients with metastasis was significantly higher than that in primary PCa (P=0.001) and begin prostate hyperplasia (BPH) patients (P<0.001). In addition, the increased TMEM45B expression was positively related with a higher possibility of biochemical recurrence (P=0.016), distant metastasis occurrence(P<0.001) and overall patient survival (P=0.07). Moreover, TMEM45B expression was considered as an independent risk factor for metastasis of PCa based on multivariate logistic regression. Kaplan-Meier analysis showed that patients with elevated TMEM45B had a shorter biochemical recurrence free survival (RFS). For primary PCa patients, subgroup analysis showed that there was a significant association between TMEM45B expression and clinical features in primary PCa cohort. Meanwhile, cases with elevated TMEM45B were more likely to develop metastasis compared to the normal group among N0 primary PCa patients (P=0.010). Primary PCa patient cohort TCGA was used to validate the results, and an obvious relationship was found between TMEM45B and clinical characteristic of PCa (T/N stage, Gleason score, Recurrence / Progress). Furthermore, a significant poor disease free survival (DFS) was investigated in high-level of TMEM45B patients compared with the other remaining cases (P=0.007). Taken together, the increased expression of TMEM45B appears to be significantly associated with prostate carcinoma progression and metastasis which provide a new prognostic biomarker for predicting metastatic potential of PCa patients, especially for primary PCa.

Construction, identification, and immunogenic assessments of an HSV-1 mutant vaccine with a UL18 deletion.

HSV-1 is a mucosal and nerve pathogen, whose morbidity shows an increasing tendency. Although several antiviral drugs exist, there is no cure for viral latency for virtually all carriers. There is an urgent need for an HSV-1 vaccine to control infection and limit its spread and recurrence. The UL18 gene, encoding a vital component of capsids, is one of the essential genes of HSV-1. Deletion of UL18 from HSV-1 may be exploited as a new approach to develop an attenuated vaccine. The purpose of this study was to construct a DNA vaccine with a full-length UL18 gene deletion of the HSV-1 genome that can induce an effective immune response. A UL18-knockdown plasmid (BAC-HSV-1ΔUL18) was constructed using the bacterial markerless gene knockout system, consisting of the functional pREDI plasmid and BAC-HSV-1 plasmid. Mice were immunized weekly for 3 weeks, and at 1 week post immunization, blood and splenocyte samples of vaccinated and control groups of mice were prepared for immunogenicity assessment. The level of immune response was evaluated using a DTH assay, cytokine determination, and splenocyte proliferation assay. Combination of the pREDI plasmid and BAC-HSV-1 plasmid provides an effective bacterial markerless gene knockout system. Using two-step homologous recombination with the UL18 homologous recombination fragment constructed by multistep PCR amplification, BAC-HSV-1ΔUL18 plasmid vaccine was successfully constructed and was found to significantly enhance cellular immune responses.

[Effect of aspirin on breast cancer stem cells and stemness of breast cancer].

Objective: To explore the effect of aspirin on the stemness of breast cancer cells and apoptosis induction of breast cancer stem cells. Methods: The 4T1 cells cultured with stem cell culture medium were screened, and immunofluorescence technique, flow cytometry and tumor-forming experiment in vivo were applied to test stem cell characteristics of the tumor spheres. After dealt with aspirin, the apoptosis rate of 4T1 stem cells was analyzed by flow cytometry. The 4T1 cells were cultured in vitro and treated with aspirin, then flow cytometry analysis was used to detect the expression of aldehydedehy drogenase1 (ALDH1), and the expression of stemness genes was tested by Western blot . Then, after culturing the cells with medium containing basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), B27 and N2, the ability of sphere-forming was observed and recorded by microscopy. In vivo BALB/c mice inoculated with 4T1 stem cells were randomly divided into the control group, 10 mg/kg, 30 mg/kg and 100 mg/kg aspirin groups. After 10 days, the mice were dealt with aspirin or NS for 15 days, then the tumor growth was observed and recorded. Results: The ratio of ALDH1 positive cells was up to 78.55%, and 4T1 tumor sphere had a postive expression of ALDH1 and sex determining region Y-box 2 (SOX2). In vivo tumorigenesis abilities of tumor sphere with 1×10(2) 4T1 stem cells could be 75%, while the ratio of normal cells was zero. The ratio of Aspirin-induced apoptosis of 4T1 stem cells at early stage and and late stage increased from 0.36% to 21.61%, and from 4.21% to 21.38%, respectively. Flow cytometry and Western blot assay results indicated that aspirin could reduce the expression of ALDH1, SOX2, octamer-binding transcription factor 4 (OCT4) and NANOG in 4T1 cells. Sphere-forming experiments results showed that aspirin could inhibit sphere forming ability of breast cancer cells. In vivo, aspirin inhibited the growth of tumors with a dose-dependent manner. Conclusion: Aspirin could induce apoptosis of cancer stem cells and reduce stemness of breast cancer, and thus play a growth-inhibiting action on breast cancer.