Objective:To evaluate the effectiveness and prognosis of emergent transcatheter aortic valve replacement (TAVR) and to provide standardized procedural suggestion for the development of emergent TAVR in China.Methods:From January 2020 to April 2021, 12 patients who underwent emergent or salvage TAVR in the Second Affiliated Hospital Zhejiang University School of Medicine were retrospectively enrolled from the TORCH registry (Transcatheter Aortic Valve Replacement Single Center Registry in Chinese Population, a prospective cohort study; NCT02803294). Baseline, periprocedural and 30-day follow up data were collected. Post-operative data were compared with pre-operative data using Paired-Samples test.Results:Patients’ median Society of Thoracic Surgeons score (STS score) was 15.432%. There was a significant decrease of mean gradient after emergent TAVR procedure (1.69 m/s vs. 4.90 m/s, P<0.01). During the 30-day follow up, there were 1 patient (8.3%) died and 2 patients received permanent pacemaker implantation. No disabling stroke, acute kidney injury, major vascular complication occurred during the first month after emergent TAVR. Among the survival patients, there was a significant releasing of heart failure symptoms to New York Heart Association function stage Ⅰ/Ⅱ in 81.8% patients at 30-day follow up. Left ventricular ejection fraction also improved significantly from (47.4±9.5)% to 58.8±8.0% ( P= 0.026). The mean gradient were (1.57±0.30) cm 2 and no patients had a moderate or severe paravalvular leakage. Besides, a significant decrease of pro-B-type natriuretic peptide (1 089.9 pg/mL vs. 12 215.5 pg/mL , P=0.001) and troponin T (0.020 ng/mL vs. 0.337 ng/mL, P=0.003) were found at 30 days after emergent TAVR. Conclusions:For patients with severe aortic stenosis and acute cardiac decompensated, emergent TAVR is a safe and effective rescue treatment.

Objective:To investigate the role of hydrogen-rich salt water in improving depression-like symptoms and its possible molecular mechanism in rats.Methods:The experiment was divided into two stages. In the first stage, 35 healthy male SD rats were randomly divided into control group, model group, high-dose group, medium-dose group, and low-dose group ( n=7); rats in the control group and model group were gavaged with 8 mL/kg normal saline per d, and rats in the high-dose group, medium-dose group, and low-dose group were fed with 8 mL/kg hydrogen-rich saline water (containing 2, 1, and 0.5 ppm hydrogen) per d; except for the control group, the other groups were depressed with chronic unpredictable mild stimulation (CUMS) for 4 weeks. In the second stage, 30 healthy male SD rats were randomly divided into hydrogen water group, hydrogen water+fluoxetine group, and nuclear factor erythroid 2-related factor 2 (Nrf2) inhibition group ( n=10); optimal hydrogen concentration (0.8 ppm) hydrogen-rich saline water (8 mL/kg) per d was given to rats of these 3 groups by gavage; fluoxetine (5 mg/kg) by gavage was given to the hydrogen-water+fluoxetine group, and all-transretinoic acid (10 mg/kg) by gavage was given to the Nrf2 inhibition group; CUMS was given for 4 weeks in these 3 groups. Rats were weighed at fixed times at each weekend. Four weeks after intervention, the total distance and average speed of rats in each group were determined by open field test. After open field test, blood was collected from the orbital veins from all rats; serum superoxidase dismutase (SOD) and malondialdehyde (MDA) contents were determined by ELISA. The expressions of brain-derived neurotrophic factor (BDNF), heme oxygenase-1 (HO-1), Nrf2, and phosphorylated Nrf2 (p-Nrf2) in the hippocampal CA3 region were detected by Western blotting. Results:(1) In the first stage, after 3 and 4 weeks of intervention, as compared with the model group, the body weight of the rats in the high-dose group, medium-dose group, and low-dose group increased significantly ( P<0.05). As compared with the model group, the medium-dose group, and low-dose group had significantly increased total distance and average speed, significantly increased serum SOD content, significantly decreased serum MDA content, significantly increased BDNF and HO-1 expressions and decreased p-Nrf2 expression in the CA3 region of the hippocampus ( P<0.05). (2) In the second stage, after 3 and 4 weeks of intervention, as compared with the Nrf2 inhibition group, the body weight of the hydrogen water group and hydrogen water+fluoxetine group increased significantly ( P<0.05). As compared with the Nrf2 inhibition group, the hydrogen water group and hydrogen water+fluoxetine group had significantly increased total distance and average speed, significantly increased serum SOD content, significantly decreased serum MDA content, statistically increased BNDF and HO-1 expressions in the CA3 region of the hippocampus, and the hydrogen water+fluoxetine group had significantly increased Nrf2 and p-Nrf2 expressions in the CA3 region of the hippocampus ( P<0.05). As compared with the hydrogen water group, the hydrogen water+fluoxetine group had significantly increased BNDF and HO-1 expressions and increased p-Nrf2 expression in the CA3 region of the hippocampus ( P<0.05). Conclusion:Hydrogen-rich salt water can increase the serum SOD and reduce the serum MDA, increase the BDNF and HO-1 protein expressions in the hippocampal areas of depressed rats, thereby improving the depression-like symptoms; the synergistic effect of hydrogen-rich saline water and fluoxetine on anti-depression may be related to antioxidant effect of Nrf2 signaling.

The use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the first line treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC), but drug resistance will be acquired within 1-2 years, and the following treatment efficacy is poor. The invention of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors has dramatically changed the situation of tumor treatment. PD-1/PD-L1 inhibitors are less effective in patients with NSCLC harboring EGFR mutation. It is a challenge to make patients with EGFR-mutated advanced NSCLC benefit from anti-PD-1/PD-L1 therapy. In this paper, the research progress on the impact of EGFR mutation on the immune status of NSCLC and related clinical studies in recent 5 years are reviewed.
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Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; B7-H1 Antigen/metabolism* ; Lung Neoplasms/pathology* ; Immune Checkpoint Inhibitors ; Ligands ; Mutation ; ErbB Receptors/metabolism* ; Protein Kinase Inhibitors/therapeutic use*

BACKGROUND: The mortality rate of lung cancer meningeal metastasis is extremely high. Circulating tumor DNA (ctDNA) has been confirmed to be contain the genomic alterations present in tumors and has been used to monitor tumor progression and response to treatments. Due to the presence of blood-brain barrier and other factors, peripheral blood ctDNA cannot reflect the information of brain lesions for patients with meningeal metastases. However, cerebrospinal fluid ctDNA as a test sample can better reflect the genetic status of intracranial tumors and guide clinical targeted treatment of intracranial lesions. This study explored the feasibility of cerebrospinal fluid ctNDA for evaluating non-small cell lung cancer (NSCLC) meningeal metastasis and the potential clinical value of cerebrospinal fluid ctDNA detection in NSCLC meningeal metastasis. METHODS: A total of 21 patients with NSCLC meningeal metastasis were included. Tumor genomic variation was performed on the cerebrospinal fluid and peripheral blood samples of patients by second-generation gene sequencing technology. The situation was examined, and pathological evaluation of cerebrospinal fluid cytology and head magnetic resonance imaging (MRI) enhanced examination were performed. RESULTS: ctDNA was detected in the cerebrospinal fluid of 21 patients. The sensitivity of cerebrospinal fluid ctDNA detection was superior to cytology in the diagnosis of meningeal metastasis (P<0.001). The detection rate and gene mutation abundance of cerebrospinal fluid were higher than plasma (P<0.001). Cerebro-spinal fluid had a unique genetic profile. In 6 patients with dynamic detection, changes of ctDNA allele fraction occurred at the same time or earlier than clinical disease changes, which could timely monitor drug resistance mechanism and relapse trend. CONCLUSIONS The detection rate of ctDNA in cerebrospinal fluid is higher than that in cytology and imaging. The detection of ctDNA in cerebrospinal fluid can reveal the specific mutation map of meningeal metastasis lesions. The dynamic monitoring of ctDNA in cerebrospinal fluid has hint significance for clinical response of lung cancer patients.

Objective A self-made tiltable treatment couch was adopted for CT simulation positioning and radiotherapy to evaluate the feasibility and effectiveness to minimize the setup errors. Methods Twenty-two patients with thoracic and abdominal tumors receiving radiotherapy in Department of Radiation Oncology,Peking Union Medical College between March and September 2016 were recruited in this study. All patients were randomly divided into the experimental(n=11)and control groups(n=11).In the study group,the tiltable treatment couch was adopted to switch the patients from the standing position to the supine position,and conventional supine position was utilized in the control group. All patients received CT positioning under spontaneous breathing. Image registration was performed according to the standard recommendations of IGRT group. The image registration data for the translational and rotation errors of CBCT were recorded and analyzed. The setup errors were calculated by four-parameter model between two groups. Results In the experimental group,the translational error of the x direction was(-0.012±0.128)cm with a variation range of(0.29-0.70 cm),(0.272±0.123)cm for the y direction(0.23-0.70 cm)and(0.089± 0.105)cm for the z direction(0.14-0.53 cm),respectively. In the control group,the translational error of the x direction was(0.006±0.198)cm(0.27-0.75 cm),(-0.108±0.396)cm for the y direction(0.56-2.08 cm)and(- 0.096± 0.176)cm for the z direction(0.34-0.89 cm), respectively. Conclusions Application of the self-made tiltable treatment couch can enhance the setup reproducibility and reduce the setup errors,especially in the y direction during radiotherapy for the thoracic and abdominal tumors.

Objective To report the clinical and peripheral neuropathological findings in two patients with autosomal recessive Charcot-Marie-Tooth disease 2K(AR-CMT2K).Methods Case one was a nine year-old girl.She had distal weakness of lower limbs for six years, with calf atrophy and contracture of Achilles tendon for three years.Case two was an eight year-old boy.He had distal weakness of lower limbs with contracture of Achilles tendon and calf muscle atrophy for three years, and proximal weakness of low limbs for two years.The motor nerve conduction velocities in median nerves were 48.1 m/s in case one and 47.6 m/s in case two.The compound motor action potential amplitude of median nerves decreased by 46% in case one and 69% in case two.Sural nerve biopsies and gene targeted next-generation sequencing were performed in both patients.Results Density of myelinated fibers was 8 407/mm2 in case one and 7 714/mm2 in case two.The ratio of myelinated fibers with diameter over 8 μm was 2.6% in case one and 0 in case two.Both patients had small regenerating cluster of myelinated fibers.Thin myelinated fibers appeared in case one.In case two, atypical onion bulb formations with focal folded myelin appeared, and electromicroscopy revealed mitochondrial aggregate in axons.Compound heterozygous mutations of ganglioside-induced differentiation associated protein 1 gene were detected in both patients, including c.767A>G(p.H256R) and c.466G>A (p.A156T) in case one and c.767A>G and 845G>A(p.R282H) in case two.Conclusions Contracture of Achilles tendon may appear in early childhood of AR-CMT2K patients.The main pathological changes in sural nerve are loss of large myelinated fibers, mitochondrial aggregate in axons and myelin abnormalities.

Objective To study the perioperative nursing of patients with uterine myoma complicated with diabetes mellitus.Methods A total of 120 patients with hysteromyoma and diabetes mellitus treated in our hospital were randomly divided into two groups, 60 patients in the observation group were given self-care, and 60 patients in the control group were given routine care, compliance, self-care ability, islet injection, diet control their blood glucose detection, postoperative anal exhaust time, wound healing time, toilet time and bed-off time after surgery, urination were observed.Results After the nursing, the observation group''s compliance, self-care ability, islet injection, diet control their blood glucose detection were significantly better, the postoperative anal exhaust time, incision healing time, first toileting time and postoperative ambulation time were shorter than that in the control group, there were significant differences between the two groups (P<0.05).Uroschesis and induced uresis patients in the observation group were significantly higher than the control group (P<0.05).Conclusion Self-care measures in patients with uterine myoma complicated with diabetes mellitus can promote the early rehabilitation and improve the nursing effect of patients with diabetes mellitus.

Objective To study the perioperative nursing of patients with uterine myoma complicated with diabetes mellitus.Methods A total of 120 patients with hysteromyoma and diabetes mellitus treated in our hospital were randomly divided into two groups, 60 patients in the observation group were given self-care, and 60 patients in the control group were given routine care, compliance, self-care ability, islet injection, diet control their blood glucose detection, postoperative anal exhaust time, wound healing time, toilet time and bed-off time after surgery, urination were observed.Results After the nursing, the observation group''s compliance, self-care ability, islet injection, diet control their blood glucose detection were significantly better, the postoperative anal exhaust time, incision healing time, first toileting time and postoperative ambulation time were shorter than that in the control group, there were significant differences between the two groups (P<0.05).Uroschesis and induced uresis patients in the observation group were significantly higher than the control group (P<0.05).Conclusion Self-care measures in patients with uterine myoma complicated with diabetes mellitus can promote the early rehabilitation and improve the nursing effect of patients with diabetes mellitus.

Objective To investigate the prevalence and risk factors of highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (LD) in patients with acquired immunodeficiency syndrome (AIDS) treated with HAART in China.Methods A total of 137 AIDS patients treated with HAART for more than 2 years were analyzed.Sixteen clinical parameters (including gender,age,baseline body mass index,baseline human immunodeficiency virus [HIV] viral load,stage of disease,routes of HIV transmission,baseline CD4+ T lymphocyte count,white blood cell count,fasting plasma glucose level,serum triglycerides level,serum cholesterol level and other laboratory results,and HAART regimens) that might be associated with HAART-LD occurrence were evaluated using Cox proportional hazards models.Results HAART regimens were significantly correlated with HAART-LD (P=0.031),while the remaining 15 factors were not associated with the risk of HAART-LD (all P＞0.05).Patients who received stavudine d4T)-containing regimen was 2.684 times more likely to develop HAART-LD than patients who received zidovudine (AZT)-containing regimen (95 ％ CI:1.302-5.531,P=0.007) ; HAART-LD prevalence rates were gradually increased with treatment duration in both groups.First HAART-LD was seen at 24 weeks in both d4T group and AZT group,and the prevalence rates were 2.7％,1.6％ at 24 weeks,27.0％,7.9％ at 48 weeks and 37.8％,15.9％ at 96 weeks respectively.The prevalence of HAART-LD in d4T group was much higher than that in AZT group and the difference was statistically significant (x2 =8.285,P=0.004).Conclusions HAART regimen is an independent predictor of HAART-LD.HAART-LD tend to occur more frequently in patients treated with d4T or AZT,especially d4T.Our study recommends to avoid the use of d4T-contained HAART regimen.

Objective To explore whether the mitochondrial toxicity markers of peripheral blood mononuclear cells (PBMC)are of significance in monitoring mitochondrial toxicity during highly active antiretroviral therapy (HAART)in patients with acquired immune deficiency syndrome (AIDS).Methods Mitochondrial DNA (mtDNA),mitochondrial thymidine kinase (TK2 )and p53-inducible ribonucleotide reductase small subunit 2 (p53R2 )were selected as mitochondrial toxicity markers.The expression changes of theses markers of PBMC in 22 AIDS patients were detected by real time quantitative polymerase chain reaction (q-PCR)at baseline,48 weeks and 96 weeks after initiation of the treatment. All the patients received stavudine/zidovudine and lamivudine as the mainstay of the HAART regimen. Independent-samples t test was used.Results The relative expression level of mtDNA in patients before HAART was 3.27 ± 0.94,and decreased to 2.16±0.85 at week 48 and 1 .66±0.66 at week 96, respectively.The differences were both significant compared with the level prior to the treatment (t =-3.90,P <0.01 and t =-6.29,P <0.01 ,respectively).The relative expression level of TK2 before HAART was 0.37 ±0.13,and increased to 1 .01 ±0.25 at week 48 and 2.13 ±0.61 at week 96 of the treatment.After pairwise comparisons of the three pairs of data (pre-HAART vs week 48 of the treatment,pre-HAART vs week 96 of the treatment and week 48 vs week 96 of the treatment),the differences were all significant (t = 10.77,8.00 and 3.56,respectively;all P < 0.01 ).The relative expression level of p53R2 was 0.86±0.39 before HAART,but gradually increased to 2.36 ±1 .14 and 7.73±0.65 ,respectively,at week 48 and week 96 of the treatment.The differences in p53R2 levels among three groups after pairwise comparison were all significant (t=3.27,12.26 and 13.25,respectively;all P < 0.01 ).Conclusions The expression levels of mtDNA,TK2 and p53R2 in PBMC could change significantly during HAART in AIDS patients,which might be used as indexes for monitoring mitochondrial toxicity.