Objective To summarize and analyze the preliminary clinical outcomes of the KokaclipTM transcatheter edge-to-edge mitral valve repair system for severe degenerative mitral regurgitation (DMR). Methods This study was a single-arm, prospective, single-group target value clinical trial that enrolled patients who underwent the KokaclipTM transcatheter edge-to-edge repair (TEER) system for DMR in the Department of Heart Surgery of Guangdong Provincial People's Hospital, Guangdong Cardiovascular Institute from June 2022 to January 2023. Differences in the grade of mitral regurgitation (MR) during the perioperative and follow-up periods were compared, and the incidences of adverse events such as all-cause death, thoracotomy conversion, reoperation, and severe recurrence of MR during the study period were investigated. Results The enrolled patient population consisted of 14 (50.0%) females with a mean age of 70.9±5.4 years. Twenty-eight (100.0%) patients were preoperatively diagnosed with typeⅡ DMR, with a prolapse width of 12.5 (11.0, 16.1) mm, a degree of regurgitation 4+ leading to pulmonary venous reflux, and a New York Heart Association cardiac function class≥Ⅲ. All patients completed the TEER procedure successfully, with immediate postoperative improvement of MR to 0, 1+, and 2+ grade in 2 (7.1%), 21 (75.0%), and 5 (17.9%) patients, respectively. Mitral valve gradient was 2.5 (2.0, 3.0) mm Hg. Deaths, thoracotomy conversion, or device complications such as unileaflet clamping, clip dislodgement, or leaflet injury were negative. Twenty-eight (100.0%) patients completed at least 3-month postoperative follow-up with a median follow-up time of 5.9 (3.6, 6.8) months, during which patients had a mean MR grade of 1.0+ (1.0+, 2.0+) grade and a significant improvement from preoperative values (P<0.001). There was no recurrence of ≥3+ regurgitation, pulmonary venous reflux, reoperation, new-onset mitral stenosis, or major adverse cardiovascular events. Twenty-two (78.6%) patients’ cardiac function improved to classⅠorⅡ. Conclusion The domestic KokaclipTM TEER system has shown excellent preliminary clinical results in selected DMR patients with a high safety profile and significant improvement in MR. Additional large sample volume, prospective, multicenter studies, and long-term follow-up are expected to validate the effectiveness of this system in the future.

Objective:To study the position of computed tomography(CT)slice of marker points of radiotherapy,which was determined by control scan(CS)method,on the application effect of patients with head and neck tumors who received radiotherapy.Methods:Based on Control Scan(CS)method,a calculator program of mark-point slice position was made,which was an enterprise WeChat program that could be used in calculating position and CT position scan of patients with head and neck tumor(slice thickness was 3mm).A total of 60 patients with head and neck tumor were selected,and the patients who underwent CT positioning scan by using CS method were divided into observation group,and patients who underwent CT position scan by using conventional method were divided into control group,with 30 cases in each group.The number of cases with three metal marker points displayed at the same slice,and the number of slices containing the CT images of marker point between the located CT scan were compared.Results:The number of patients in the observation group and the control group who showed three markers at the same level at the same time were respectively 26 cases and 13 cases,and observation group increased by 13 cases(43.4%)than control group,and the difference was significant(x2=12.382,P<0.05).The number of CT images with only 1 slice of observation group and control group were respectively 4 cases and 0 cases,which increased by 4 cases(13.3%)than the control group,and the difference was significant(x2=2.411,P<0.05).Conclusions:The CT localization scan of radiotherapy,which uses CS to assist patients with head and neck tumor,can precisely calculate and obtain the primary position of target of CT localization scan.It can take the images of 3 mental marker points of patient who receives radiotherapy to occur at the same CT slice as soon as possible,which has better application effect.It can effectively improve the convenience and work effectiveness of radiotherapy.

Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Purpose: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti–programmed cell death-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. Materials and Methods: This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child-Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. Results: During a median follow-up of 11.23 months (range, 3.07 to 34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The 2-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. Conclusion Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.
Animals ; Neurons/physiology* ; Mice ; Brain/physiology* ; Mice, Inbred C57BL ; Somatosensory Cortex/physiology* ; Neural Pathways/physiology* ; Hippocampus/physiology* ; Mice, Transgenic ; Male ; Brain Mapping ; Nerve Net/physiology* ; Substantia Nigra/physiology* ; Tomography, Optical/methods*

Objective     To evaluate the early clinical outcomes of the Renatus® balloon-expandable valve in the treatment of severe aortic stenosis. Methods    From November 2021 to April 2022, a total of 38 patients who received Renatus® balloon-expandable valve for severe aortic stenosis in Guangdong Provincial People's Hospital were included. There were 22 males and 16 females, with an average age of 73.7±5.3 years. Mean aortic gradient and peak aortic jet velocity at baseline, post-procedure, and follow-up were compared. Clinical outcomes including all-cause mortality, perivalvular leakage, serious adverse cardiovascular events and the occurrence of permanent pacemaker implantation were assessed. Results    All patients completed the procedure successfully without conversion to thoracotomy or perioperative death. The post-implant mean aortic pressure gradient was decreased from 41.5 (27.8, 58.8) mm Hg to 6.0 (3.0, 8.0) mm Hg, and the peak aortic jet velocity was also decreased from 4.1±0.9 m/s to 1.7±0.4 m/s (P<0.001). Pacemakers were required in 2 (5.3%) patients. The median follow-up time was 27.5 (23.0, 87.5) d, with a follow-up rate of 100.0%. The mean aortic gradient was 8.0 (7.0, 10.8) mm Hg and peak aortic jet velocity was 2.0±0.3 m/s, showing significant improvement compared with those in the preoperative period (P<0.001). No severe aortic regurgitation or paravalvular leak was observed. There was no serious cardiovascular adverse event or reoperative event during the study period. Conclusion    Transcatheter aortic valve replacement with the domestic Renatus® balloon-expandable valve system is a safe and effective procedure for selected patients with severe aortic stenosis who are at high risk or not candidates for surgical aortic valve replacement.

Objective To investigate the correlation of peripheral blood lymphocyte, T-cell, Th-cell, and Ts-cell counts with the development of checkpoint-inhibitor-related pneumonitis in NSCLC. Methods The clinical data of 85 patients with NSCLC treated with immune checkpoint inhibitors (ICIs) were retrospectively analyzed.Paired t-test was used to analyze lymphocyte changes.ROC curves were utilized to analyze predictive performance.The Spearman correlation coefficient test was conducted to analyze the linear relationship between lymphocyte changes and CIP grade. Results A statistically significant decrease in lymphocyte, T-cell, Th-cell, and Ts-cell counts from the baseline was observed in patients at the onset of CIP (P < 0.05), whereas no such change was observed in the control group.ROC curve analysis revealed AUCs of 0.867, 0.843, 0.865, and 0.843 for lymphocyte, T-cell, Th-cell, and Ts-cell counts, respectively.A linear relationship was found between the percentage decrease in lymphocyte, T-cell, and Ts-cell counts from the baseline and the severity of CIP (P < 0.05). Conclusion Decreased lymphocyte, T-cell, Th-cell, and Ts-cell counts have a predictive value for the development of CIP, and the lymphocyte count change has the greatest predictive value.The percentage decrease in lymphocyte, T-cell, and Ts-cell counts from the baseline is correlated with the severity of CIP.

Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association update the guidelines for the prevention and treatment of chronic hepatitis B (version 2022) in 2022. The latest guidelines recommend more extensive screening and more active antiviral treating for hepatitis B virus infection. This article interprets the essential updates in the guidelines to help deepen understanding and better guide the clinical practice.
Humans ; Hepatitis B, Chronic/drug therapy* ; Hepatitis B/drug therapy* ; Hepatitis B virus ; Antiviral Agents/therapeutic use* ; Gastroenterology

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
Humans ; Apoptosis Inducing Factor/metabolism* ; NAD/metabolism* ; Dimerization ; Apoptosis