[Short-term efficacy and safety of cardiac contractility modulation in patients with heart failure].

Objective: To investigate the short-term efficacy and safety of cardiac contractility modulation (CCM) in patients with heart failure. Methods: This was a cross-sectional study of patients with heart failure who underwent CCM placement at the First Affiliated Hospital of Xinjiang Medical University from February to June 2022. With a follow-up of 3 months, CCM sensation, impedance, percent output, and work time were monitored, and patients were compared with pre-and 3-month postoperative left ventricular ejection fraction (LVEF) values, and 6-minute walk test distance and New York Heart Association (NYHA) cardiac function classification, and the occurrence of complications was recorded. Results: CCM was successfully implanted in all 9 patients. Seven(7/9) of them were male, aged (56±14) years, 3 patients had ischaemic cardiomyopathy and 6 patients had dilated cardiomyopathy. At 3-month postoperative follow-up, threshold was stable, sense was significantly lower at follow-up than before (right ventricle: (16.3±7.0) mV vs. (8.2±1.1) mV, P<0.05; local sense: (15.7±4.9) mV vs. (6.7±2.5) mV, P<0.05), and impedance was significantly lower at follow-up than before (right ventricle (846±179) Ω vs. (470±65) Ω, P<0.05, local sense: (832±246) Ω vs. (464±63) Ω, P<0.05). The CCM output percentage was (86.9±10.7) %, the output amplitude was (6.7±0.4) V, and the daily operating time was (8.6±1.0) h. LVEF was elevated compared to preoperative ((29.4±5.2) % vs. (38.3±4.3) %, P<0.05), the 6-minute walk test was significantly longer than before ((96.8±66.7)m vs. (289.3±121.7)m, P<0.05). No significant increase in the number of NYHA Class Ⅲ-Ⅳ patients was seen (7/9 vs. 2/9, P>0.05). The patient was not re-hospitalised for worsening heart failure symptoms, had no malignant arrhythmic events and experienced significant relief of symptoms such as chest tightness and shortness of breath. No postoperative complications related to pocket hematoma, pocket infection and rupture, electrode detachment, valve function impairment, pericardial effusion, or cardiac perforation were found. Conclusions: CCM has better short-term safety and efficacy in patients with heart failure.

[The efficacy and safety of laparoscopic radical gastrectomy after neoadjuvant chemotherapy combined with immunotherapy and targeted therapy].

Objectives: To explore the efficacy and safety of laparoscopic radical gastrectomy after neoadjuvant chemotherapy combined with immunotherapy and targeted therapy in patients with gastric cancer. Methods: A retrospective analysis of clinical and pathological data of 20 patients with locally advanced gastric cancer (clinical TNM stage T3-4aN+M0) admitted to the Cancer Hospital, Chinese Academy of Medical Sciences from July 2021 to July 2023. All patients received 3 cycles of SOX (Oxaliplatin+S-1) regimen combined with immunotherapy (Trastuzumab) and targeted therapy (Apatinib) as neoadjuvant treatment followed by laparoscopic radical gastrectomy for gastric cancer. Surgical outcomes, postoperative pathological response, and postoperative recovery were observed. Quantitative data, except for age and operation time, were expressed using Median (range). Results: Among the 20 patients, there were 18 males and 2 females, aged 41 to 73 years [(60.6±9.7) years]. All 20 patients underwent laparoscopic surgical treatment after neoadjuvant therapy, with one patient undergoing laparoscopic conversion to open total gastrectomy with partial transverse colon resection due to tumor invasion into the transverse mesocolon. Eight patients underwent totally laparoscopic radical gastrectomy, all with Billroth Ⅱ+Braun anastomosis at the distal stomach. Eleven patients underwent laparoscopic-assisted radical gastrectomy, among which total gastrectomy with Roux-en-Y anastomosis was performed in ten cases, and proximal gastrectomy with esophagogastrostomy overlap anastomosis was performed in one case. The mean operation time for the 20 patients was (165.0±34.1) minutes; intraoperative blood loss was 80 (20-100) ml; and the number of lymph nodes retrieved was 68 (21-89). Postoperative pathological TNM staging revealed stage T0N0M0 in six cases, stage Ⅰ in two cases, stage Ⅱ in three cases, and stage Ⅲ in nine cases. Six patients (30.0%) achieved pathological complete response, and nine patients (45.0%) achieved significant pathological response. The median postoperative time to flatus was 4 (1-5) days; oral intake resumed after 3 (2-5) days; and the median length of hospital stay was 13 (6-19) days. One patient developed colonic anastomotic leakage with intra-abdominal infection, and one patient developed duodenal stump leakage with intra-abdominal infection, both classified as Clavien-Dindo grade 3A complications, and improved after treatment and discharged. One patient developed gastric paresis, and two patients developed pleural effusion, classified as Clavien-Dindo grade 2 complications, and improved after treatment and discharged. There were no deaths within 30 days after discharge. Conclusions: Laparoscopic radical gastrectomy for gastric cancer after neoadjuvant treatment with the SOX regimen combined with immunotherapy and targeted therapy is safe and feasible, with satisfactory short-term efficacy. However, there is an increase in overall surgical risk and difficulty, and it is recommended to be performed in experienced gastric cancer centers.

Clinical outcomes of SMILE and WFG-LASIK used to treat myopia and astigmatism: A systematic review and meta-analysis.

PURPOSE: To evaluate the safety, efficacy and postoperative visual quality of small incision lenticule extraction (SMILE) and Wavefront-Guided Laser in situ keratomileusis (WFG-LASIK) and to analyze their efficacy in correcting astigmatism. METHODS: A systematic literature search was performed using Cochrane Collaboration methodology. Databases searched included PubMed, Embase, the Cochrane Library and Web of Science. RevMan software version 5.3.0 was used for meta-analysis. RESULTS: A total of 976 eyes were included in 8 studies, of which 539 eyes underwent SMILE and 437 eyes underwent WFG-LASIK. There were no statistically significant differences in the proportion of eyes achieving uncorrected distance visual acuity of 20/20 or better (P=0.18), the proportion of eyes within±0.50 diopter of target refraction postoperatively (P=0.10), or the postoperative magnitude of cylinder (P=0.10). Regarding the Alpins vector analysis of astigmatism, there was no statistically significant difference in the surgical magnitude of error (P=0.09) between the two groups. WFG-LASIK has a lower surgical angle of error (P= 0.002) and higher surgical correction index of cylinder (P=0.03) than SMILE. In terms of aberrations, higher order aberrations (P=0.46), spherical aberrations (P=0.22) and trefoil (P=0.56) were not statistically different, while WFG-LASIK induced less coma than SMILE surgery (P=0.02). CONCLUSION: Both SMILE and WFG-LASIK are safe and effective ways to correct myopia and astigmatism. Compared with SMILE, WFG-LASIK has a lower surgical angle of error, higher surgical correction index of cylinder and induces less coma.

[Analysis of factors related to systemic embolism in patients≥75 years old with non-valvular atrial fibrillation].

Objective: To explore the related risk factors for systemic embolism (SE) in patients aged≥75 years with non-valvular atrial fibrillation (NVAF). Methods: A case-control study. NVAF patients aged≥75 years who were hospitalized at the First Affiliated Hospital of Xinjiang Medical University from October 2018 to October 2020 were divided into no SE (n=1 127) and SE (n=433) groups according to the occurrence of SE after NVAF. Multivariate logistic regression was used to analyze SE-related factors in patients with NVAF without anticoagulation treatment. Results: In the multivariate model, the following factors were associated with an increased risk of SE in patients with NVAF: history of AF≥5 years [odds ratio (OR)=2.75, 95% confidence interval (CI) 1.98-3.82, P<0.01], lipoprotein(a)>300 g/L (OR=2.07, 95%CI 1.50-2.84, P<0.01), apolipoprotein (Apo)B>1.2 g/L (OR=1.91, 95%CI 1.25-2.93, P=0.003), left ventricular ejection fraction (LVEF) of 30%-49% (OR=2.45, 95%CI 1.63-3.69, P<0.01), left atrial diameter>40 mm (OR=1.54, 95%CI 1.16-2.07, P=0.003), and CHA2DS2-VASc score≥3 (OR=15.14, 95%CI 2.05-112.13, P=0.01). ApoAI>1.6 g/L was negatively correlated with the occurrence of SE (OR=0.28, 95%CI 0.15-0.51, P<0.01). Conclusions: History of AF≥5 years, lipoprotein(a)>300 g/L, elevated ApoB, left atrial diameter>40 mm, LVEF of 30%-49%, and CHA2DS2-VASC score≥3 are independent risk factors for SE whereas ApoAI>1.6 g/L is a protective factor against SE in patients with NVAF.

[Effects of vaccines on the viral negative conversion of children with COVID-19].

Objective: To explore the effect of vaccination on viral negative conversion of children with COVID-19. Methods: A retrospective cohort study was conducted. A cohort of 189 children aged 3-14 years with COVID-19 admitted to Renji Hospital (South branch) of Shanghai Jiao Tong University School of Medicine from April 7th to May 19th 2022 was enrolled in the study. According to the vaccination status, the infected children were divided into an unvaccinated group and a vaccinated group. Age, gender, severity, clinical manifestations, and laboratory tests, etc. were compared between groups, by rank sum test or chi-square test. The effects of vaccination on viral negative conversion were analyzed by a Cox mixed-effects regression model. Additionally, a questionnaire survey was conducted among the parents of unvaccinated children to analyze the reasons for not being vaccinated. Results: A total of 189 children aged 3-14 years were enrolled, including 95 males (50.3%) and 94 females (49.7%), aged 5.7 (4.1,8.6) years. There were 117 cases (61.9%) in the unvaccinated group and 72 cases (38.1%) in the vaccinated group. The age of the vaccinated group was higher than that of the unvaccinated group (8.8 (6.8, 10.6) vs. 4.5 (3.6, 5.9) years, Z=9.45, P<0.001). No significant differences were found in clinical manifestations, disease severity, and laboratory results between groups (all P>0.05), except for the occurrence rate of cough symptoms, which was significantly higher in the vaccinated group than in the non-vaccinated group (68.1% (49/72) vs. 50.4% (59/117),χ2=5.67, P=0.017). The Kaplan-Meier survival curve and Cox mixed-effects regression model showed that the time to the viral negative conversion was significantly shorter in the vaccinated group compared with the unvaccinated group (8 (7, 10) vs. 11 (9, 12) d, Z=5.20, P<0.001; adjusted HR=2.19 (95%CI 1.62-2.97)). For questionnaire survey on the reasons for not receiving a vaccination, 115 questionnaires were distributed and 112 valid questionnaires (97.4%) were collected. The main reasons for not being vaccinated were that parents thought that their children were not in the range of appropriate age for vaccination (51 cases, 45.5%) and children were in special physical conditions (47 cases, 42.0%). Conclusion: Vaccination can effectively shorten the negative conversion time of children with COVID-19 and targeted programs should be developed to increase eligible children's vaccination rate for SARS-CoV-2 vaccination.

Application of XOLAIR® (Omalizumab) in adolescent refractory chest tightness variant asthma.

BACKGROUND: Asthma can manifest in a variety of clinical phenotypes like cough variant asthma, chest tightness variant asthma (CTVA), and masked asthma. Patients with CTVA usually have a singular or primary complaint of chest tightness, which is often overlooked or misdiagnosed due to the lack of characteristic asthma symptoms. We hereby report a case of CTVA managed by omalizumab. CASE REPORT: A 15-year-old female patient reported to us with repeated coughing persisting for 3 weeks. Initial treatment with standard asthma drugs had minimal effect. Later during the disease, chest tightness became the primary symptom, and she was managed with steroids, ß2 receptor agonists, and leukotriene receptor agonists but without complete relief. Based on clinical signs and symptoms, the response to baseline drugs, and results of bronchial provocation test, the diagnosis was revised to CTVA, and the patient was started on Omalizumab in addition to baseline drugs, which significantly improved her condition. CONCLUSIONS: CTVA is difficult to diagnose due to its insidious symptoms and poor characteristics. Improper treatment can lead to uncontrolled disease, negative psychological issues, and reduced quality of life. Comprehensive assessment of children's airway inflammation level, lung function, bronchial provocation test, and responsiveness to drug therapy should be performed for accurate diagnosis. Omalizumab in combination with standard drugs can significantly improve the outcomes of CTVA.

[Correlation between abnormal left atrial appendage function and thrombotic events in patients with non-valvular atrial fibrillation].

Objective: To investigate the association between abnormal left atrial appendage function and thrombotic events in patients with non-valvular atrial fibrillation, and the independent risk factors affecting left atrial appendage function. Methods: Patients with non-valvular atrial fibrillation, who visited the Atrial Fibrillation Center of the First Affiliated Hospital of Xinjiang Medical University from June 1, 2019 to June 1, 2021, were selected. According to left atrial appendage flow velocity (LAAFV), they were divided into normal left atrial appendage function group (297 patients with LAAFV ≥ 40 cm/s) and abnormal left atrial appendage function group (85 patients with LAAFV<40 cm/s). Baseline data and transesophageal echocardiography images were collected from all the patients. The occurrence of thrombotic events was recorded. Univariate and multivariate unconditional logistic regression analyses were conducted to investigate the correlation between abnormal left atrial appendage function and the occurrence of thrombotic events. Results: There were significant differences in gender, type of atrial fibrillation, CHA2DS2-VASc score, anticoagulant therapy, total cholesterol, low-density lipoprotein cholesterol, international normalized ratio (INR), left atrial diameter, proportion of patients with right atrial enlargement, left ventricular ejection fraction, inner diameter, sum of inner diameter, depth, and sum of depth of all angles of the left atrial appendage, and incidence of thrombotic events between the two groups (all P<0.05). After adjusting for confounders, multivariate unconditional logistic regression analyses showed that abnormal left atrial appendage function was closely associated with thrombotic events (ß=1.168 P=0.002), and left atrial diameter (OR=1.084, 95%CI 1.019-1.153, P=0.011) and persistent atrial fibrillation (OR=2.323, 95%CI 1.226-4.403, P=0.010) were independent risk factors affecting left atrial appendage function. Conclusions: Abnormal left atrial appendage function is closely associated with thrombosis. The left atrial diameter and persistent atrial fibrillation were independent risk factors affecting left atrial appendage function.

UV response characteristics of mixed-phase MgZnO thin films with different structure distributions, high Iuv/Idark ratios, and fast speed MgZnO UV detectors with tunneling breakdown mechanisms.

High-performance ultraviolet (UV) detectors with both high responses and fast speeds are hard to make on homogeneous crystal semiconductor materials. Here, the UV response characteristics of mixed-phase MgZnO thin films with different internal structure distributions are studied. The mixed-phase MgZnO-based detector with the given crystal composition has a high response at both deep UV light (96 A W-1 at 240 nm) and near UV light (80 A W-1 at 335 nm). Meanwhile, because of the quasi-tunneling breakdown mechanism within the device, the high-response UV detector also shows a fast response speed (tr = 0.11 µs) and recovery speed (td1 = 26 µs) at deep UV light, which is much faster than both low-response mixed-phase MgZnO-based UV detectors with other structure constitutions and reported high-response UV devices on homogenous crystal materials. The Idark of the device is just 4.27 pA under a 5 V bias voltage, so the signal-to-noise ratio of the device reached 23852 at 5.5 uW cm-2 235 nm UV light. The new quasi-tunneling breakdown mechanism is observed in some mixed-phase MgZnO thin films that contain both c-MgZnO and h-MgZnO parts, which introduce a high response, signal-to-noise ratio, and fast speed into mixed-phase MgZnO-based UV detectors at weak deep UV light.

UV response characteristics of mixed-phase MgZnO thin films with different structure distribution and high Iuv/Idarkratio and fast speed MgZnO UV detector with tunneling breakdown mechanism.

High performance UV detector with both high response and fast speed is hard to made on homogeneous crystal semiconductor materials. Here, the UV response characteristics of mix-phase MgZnO thin films with different internal structure distribution are studied, the mix-phase MgZnO based detector with given crystal composition own high response at both deep UV light (96 A/W at 240nm) and near UV light (80 A/W at 335nm). Meanwhile, because of quasi-tunneling breakdown mechanism within the device, the high response UV detector also show fast response speed (tr= 0.11 µs) and recovery speed (td1=26 µs) at deep UV light, which are much faster than the both low response mix-phase MgZnO based UV detectors with other structure constitution and reported high response UV devices on homogenous crystal materials. The Idarkof the device is just 4.27 pA under a 5 V bias voltage, so the signal to noise ratio of the device reached 23852 at 5.5uW/cm2 235nm UV light. Therefore, new quasi-tunneling breakdown mechanism is observed in some mix-phase MgZnO thin film that contains both c-MgZnO and h-MgZnO parts, which introduced high response, signal to noise ratio and fast speed into mix-phase MgZnO based UV detector at weak deep UV light.

[Ovarian Sertoli-Leydig cell tumors: DICER1 hotspot mutations and associated clinicopathological features].

Objective: To investigate DICER1 hotspot mutations in ovarian Sertoli-Leydig cell tumor (SLCT) and its associated clinicopathological features. Methods: Forty-three SLCTs and 40 other sex cord-stromal tumors (SCSTs) diagnosed between 2010 and 2017 at Fudan University Shanghai Cancer Center were examined for somatic DICER1 hotspot mutations by Sanger sequencing. The associations between mutation status and clinicopathological features, including patient age, tumor differentiation and recurrence, were analyzed. Results: Somatic DICER1 mutations were found in 51% (22/43) of SLCTs, while none in the other 40 SCSTs. The most common mutation of DICER1 was p.D1709N in exon 24 (41%, 9/22) and the second most common mutation of DICER1 was p.E1813K in exon 25 (14%, 3/22). A novel frameshift mutation (c.5464delG, p.M1837fs*16) was identified in one SLCT with microcystic pattern. Mutations were more likely to occur in patients under forty years of age (P=0.046), whereas no significant associations were found between DICER1 mutations and clinical symptoms, morphology or tumor recurrence. Conclusions: Somatic DCIER1 hotspot mutations are specifically found in SLCT and may serve as an ancillary marker in differential diagnosis of SLCT from other SCST. The mutations occur more often in young patients (<40 years old). Additional studies are warranted to examine the associations between DICER1 mutations and clinicopathological features and prognosis of SLCT.

[Pediatric colonoscopy findings and changing patterns from Beijing in one institutional experience over 12 years].

OBJECTIVE: To investigate the demographics and diagnostic yield in a cohort of Chinese pediatric patients undergoing colonoscopy in one institution over 12 years. METHODS: The study participants were consecutive patients aged <18 years that underwent their first colonoscopy in the endoscopy center at Peking University Third Hospital between Jan. 1, 2005 and Dec. 31, 2017. Demographic, endoscopic, and pathological findings were collected. According to the age of the patients, they were divided into 0-3 year-old group, 4-6 year-old group, 7-14 year-old group and 15-17 year-old group. The patients were also divided into 2005-2011 group and 2012-2017 group, according to the time of colonoscopy. RESULTS: The cohort consisted of 326 patients, including 205 boys (62.9%) and 121 girls (37.1%). In the study, 31 patients (9.5%) were in 0-3 year-old group, 28 (8.6%) were in 4-6 year-old group, 96 (29.4%) were in 7-14 year-old group and 171 (52.5%) in 15-17 year-old group. The terminal ileum intubation success rate was 90.5% (295/326). No serious complications such as hemorrhage or perforation occurred during the procedures. The cleaning effect was good in 92.3% (301/326) of the patients. A total of 204 patients (62.6%) received a positive diagnosis under colonoscopy. 27.0% (88/326) of the patients was diagnosed as nonspecific colitis or terminal ileitis. 46 (14.1%) with inflammatory bowel disease (IBD) and 39 (12.0%) with polyp. The diseases were significantly different among the different age groups. The highest IBD diagnostic rate was found in 0-3 year-old group (7/31, 22.5%), while the highest polyp finding rate was in 4-6 year-old group (8/28, 28.6%). The number of the patients in 0-3 year-old group was significantly increasing in 2012-2017 group compared with 2005-2011 group (27/191 vs. 4/135, P=0.001), while the terminal ileum intubation success rate was higher (179/191 vs. 116/135, P=0.037). However, comparisons between years 2005-2011 and 2012-2017 showed that neither IBD nor polyp detection rate changed significantly (P=0.850). CONCLUSION: Colonoscopy in pediatric patients was a safe and effective procedure. Colitis or terminal ileitis was the primary finding during colonoscopy while IBD was the second one, and polyp was the third. However, the diagnostic yield did not change significantly. IBD was not as quickly increased in our hospital as it was in South China.

Regulatory effects of CCDC3 on proliferation, migration, invasion and EMT of human cervical cancer cells.

OBJECTIVE: To elucidate the potential effects of Coiled coil domain-containing 3 (CCDC3) on proliferative, migratory, invasive potentials and epithelial-mesenchymal transition (EMT) of human cervical cancer cells. MATERIALS AND METHODS: Protein and mRNA levels of CCDC3 in C33 and HeLa cells were determined by quantitative Real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Proliferative capacity and clonality of C33 and HeLa cells transfected with sh-CCDC3 were evaluated by cell counting kit-8 (CCK-8) and colony formation assay, respectively. Transwell assay and wound healing assay were conducted to determine the invasive and migratory potentials of cervical cancer cells with CCDC3 knockdown. Protein expressions of EMT-related genes in C33 and HeLa cells with CCDC3 knockdown were determined by Western blot. RESULTS: Transfection of sh-CCDC3 in C33 and HeLa cells markedly inhibited CCDC3 expression compared with those transfected with sh-EGFP. CCDC3 knockdown remarkably attenuated proliferative, migratory and invasive capacities. Moreover, CCDC3 knockdown inhibited protein levels of EMT-related genes in C33 and HeLa cells. CONCLUSIONS: Low expression of CCDC3 attenuated proliferative, migratory, invasive potentials and EMT of cervical cancer cells. Hence, CCDC3 may be utilized as a novel therapeutic target for cervical cancer.

[Analysis of factors relevant to primary non-response to infliximab treatment in patients with Crohn's disease].

Objective: To evaluate factors relevant to primary non-response in patients with Crohn's disease undergoing infliximab (IFX) treatment at week 14. Methods: Patients with Crohn's disease in the Third Hospital of Peking University who were subject to IFX treatment more than 3 times and followed-up for more than 14 weeks from October 2015 to October 2018 were reviewed. The response was defined by a decrease of ≥100 points from baseline in the Crohn's Disease Activity Index. The clinical data and laboratory examinations of the two groups were compared, and the treatment outcomes of non-responders were also followed up. Results: A total of 41 patients were enrolled, among which 27(65.9%) were male. The median age at treatment was 25 years, and 8 patients lost primary response (19.5%). There was no significant difference in the sex, age at diagnosis or treatment, Montreal disease type and laboratory examinations [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), hemoglobin, albumin] in the response group and non-response group at baseline phase (P>0.05). Baseline CRP decreased from 17.7 (26.2) mg/L to 2.2 (3.6) mg/L in the response group, but increased from 11.7 (9.5) mg/L to 31.6 (28.4) mg/L in the non-response group at week 14 (P=0.024). The trend of ESR change in the response group [from 23.0 (28.5) mm/h to 7.0 (8.5) mm/h] and the non-response group [from 24.5 (22.5) mm/h to 35.0 (26.5) mm/h] was similar with that of CRP (P=0.036). Hemoglobin and albumin were significantly elevated in the response group, but not in the non-response group at week 14 (P=0.593, P=0.255). Among the non-response patients, 5 were converted to responsive after the treatment protocols had been adjusted. The combined immunosuppressant treatment all obtained clinical response. Conclusions: The elevated CRP and/or ESR may serve as indicators of primary non-response (at week 14) to IFX treatment among Crohn's disease patients, and the combination of immunosuppressive agents may be one of the effective treatments after excluding infection and other causes.

[Analysis of the KCNQ1 gene mutation in 2 families with congenital long QT syndrome type 1 in Xinjiang Uygur Autonomous Region].

Objective: Present study analyzed the association betwen the postassium voltage-gated channel KQT-like subfamily member 1 gene (KCNQ1) mutation and the clinical and the electrocardiographic features in 2 pedigrees with congenital long QT syndrome type 1 (LQT1) in Xinjiang Uygur Autonomous Region. Methods: Three family members were diagnosed as LQT1 patients in 2 Uygur congenital LQT1 families, these 3 LQT1 patients served as long QT group, 24 Uygur healthy volunteers served as control group. Electrocardiogram (ECG) and the gene detection were applied to compare the ECG and molecular genetic features between the long QT group and control group, and to explore the relationship between the KCNQ1 gene mutation and the clinical and the electrocardiographic features in these 2 families with congenital long QT syndrome type 1. Results: The LQT1 was diagnosed in 3 cases of the 2 pedigrees. The common features of ECG were QTc>480 ms, prolonged ST segment, and delayed T wave. The gene test evidenced a polymorphism of KCNQ1 gene exon 13:47G➝A(R16R). The mutation of 133G➝A9(G45S) of exon 16 resulted in the change of the original glycine (G) to serine (s). The ECG of the control group were normal, and there were no KCNQ1 gene mutations in control group. Conclusion: The exon sequencing results of KCNQ1 gene in 2 Xinjiang Uygur congenital long LQT1 families showed that exon16 missense changes (133G to A (G45S)) can lead to amino acid mutation, this mutation may be a pathogenic mutation. Subsequent validation of the expanded sample will provide a reference for revealing the relationship between the KCNQ1 gene and the pathogenesis of LQT1.

Thermal pain tolerance and pain rating in normal subjects: Gender and age effects.

BACKGROUND: Thermal detection thresholds and thermal pain thresholds are important in quantitative sensory testing. Although they have been well studied for assessing somatosensory function, the investigation of thermal pain tolerance has been insufficient. The aim of this study was to explore the characteristics of thermal pain tolerance and pain ratings in healthy subjects. METHODS: Cold pain tolerance (CPTol) and heat pain tolerance (HPTol) were tested in 213 healthy adults aged 18-81 years recruited from the local community. The thermal detection and thermal pain thresholds were also tested to investigate the association with pain tolerance. The visual analogue scale (VAS) was used for assessing pain severity immediately after the thermal pain and tolerance tests. RESULTS: The normality of the CPTol and HPTol was acceptable. Most participants rated the pain induced by the CPTol and HPTol testing as moderate. HPTol was lower in women than in men (p = 0.001), but CPTol did not differ between sexes. The pain ratings of CPTol and HPTol did not differ between sexes, but significant age effects were observed. The association of the tolerance temperature with pain ratings was weak, while those of pain ratings for CPTol and HPTol were strong (r = 0.87). CONCLUSIONS: Women were more sensitive to tolerance heat pain stimuli. Younger participants reported more pain for thermal pain and tolerance tests. SIGNIFICANCE: Thermal pain tolerance and pain rating for the thermal pain tolerance temperature depend on gender and age. Women are more sensitive to heat temperatures, young people rate more pain, and the pain ratings of heat and cold are strongly correlated.

Tau-mediated iron export prevents ferroptotic damage after ischemic stroke.

Functional failure of tau contributes to age-dependent, iron-mediated neurotoxicity, and as iron accumulates in ischemic stroke tissue, we hypothesized that tau failure may exaggerate ischemia-reperfusion-related toxicity. Indeed, unilateral, transient middle cerebral artery occlusion (MCAO) suppressed hemispheric tau and increased iron levels in young (3-month-old) mice and rats. Wild-type mice were protected by iron-targeted interventions: ceruloplasmin and amyloid precursor protein ectodomain, as well as ferroptosis inhibitors. At this age, tau-knockout mice did not express elevated brain iron and were protected against hemispheric reperfusion injury following MCAO, indicating that tau suppression may prevent ferroptosis. However, the accelerated age-dependent brain iron accumulation that occurs in tau-knockout mice at 12 months of age negated the protective benefit of tau suppression against MCAO-induced focal cerebral ischemia-reperfusion injury. The protective benefit of tau knockout was revived in older mice by iron-targeting interventions. These findings introduce tau-iron interaction as a pleiotropic modulator of ferroptosis and ischemic stroke outcome.

Combination of Echinocandins and Trimethoprim/Sulfamethoxazole for the Treatment of Pneumocystis jiroveci Pneumonia After Heart Transplantation.

BACKGROUND: The echinocandins have shown anti-Pneumocystis jiroveci activity in nonhuman animal models; however, the corresponding human clinical experience has been rarely reported. We report a clinical picture of P jiroveci pneumonia (PJP) and determine the effects of concomitant therapy with echinocandins and trimethoprim (TMP)-sulfamethoxazole (SMZ). METHODS: We investigated a retrospective case series of heart transplantation (HT) recipients with PJP from July 1988 to December 2015. Recipient charts were reviewed for their demographic characteristics, underlying conditions, concomitant infections, PJP prophylaxis, TMP-SMZ dosages, adverse events, echinocandin use, oxygenation, and outcomes. RESULTS: Eleven of 451 HT recipients developed PJP after a median duration of 2.8 years after transplantation. All 11 were treated with TMP-SMZ; 5 of them were treated with echinocandins added to the standard TMP-SMZ regimen. The longest interval between transplantation and PJP development was 16.3 years. The mortality rate was 33.3% in recipients receiving TMP-SMZ alone, whereas it was 20% in those receiving echinocandins as well. The most common side effects of TMP-SMZ include nausea and vomiting, metabolic acidosis, and hyperkalemia. Five recipients developed acute psychosis after a median duration of 6 days of TMP-SMZ therapy. The incidence of psychosis increased from 25% in recipients receiving TMP at ≤15 mg/kg/d to 100% in those receiving TMP at >15 mg/kg/d. CONCLUSIONS: Echinocandins along with the standard TMP-SMZ regimen may effectively alleviate PJP developed after HT. The ideal prophylaxis duration is lifelong owing to the late onset of PJP. The typically intolerable adverse effects of TMP-SMZ therapy for PJP may necessitate dosage adjustments in some cases.