Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Objective To systematically evaluate the short-term efficacy and safety of lung subsegmentectomy and segmentectomy in the treatment of small pulmonary nodules. Methods Computer searches were conducted on PubMed, The Cochrane Library, EMbase, Scopus, Web of Science, SinoMed, Wanfang Data, VIP, and CNKI databases to collect relevant literature on the short-term efficacy and safety of lung subsegmentectomy and segmentectomy for small pulmonary nodules from the inception to April 2024. Two researchers independently screened the literature and extracted data according to inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software, and the Newcastle-Ottawa Scale (NOS) was used to assess the quality of the selected literature. Results A total of 15 retrospective cohort studies with 2417 patients were included, among whom 796 patients underwent lung subsegmentectomy and 1621patients underwent segmentectomy. The NOS scores of the included literature were all≥6 points. Meta-analysis results showed that compared with segmentectomy, lung subsegmentectomy had a lower overall postoperative complication rate [OR=0.54, 95%CI (0.39, 0.75), P<0.01] and fewer lymph nodes dissected [MD=−0.43, 95%CI (−0.81, −0.06), P=0.02]. There was no statistical difference between the two surgical methods in terms of operation time [MD=5.11, 95%CI (−4.02, 14.23), P=0.27], intraoperative blood loss [MD=−14.62, 95%CI (−29.58, 0.34), P=0.06], postoperative hospital stay [MD=−0.24, 95%CI (−0.49, 0.01), P=0.06], postoperative drainage time [MD=−0.14, 95%CI (−0.46, 0.18), P=0.40], intraoperative margin width [MD=0.10, 95%CI (−0.16, 0.35), P=0.46], or recurrence rate [OR=1.57, 95%CI (0.53, 4.61), P=0.42]. Subgroup analysis results showed that when using uniportal video-assisted thoracoscopy for surgery, compared with segmentectomy, lung subsegmentectomy had less intraoperative blood loss [MD=−15.57, 95%CI (−28.84, −2.30), P=0.02], shorter postoperative hospital stay [MD=−0.49, 95%CI (−0.63, −0.35), P<0.01], shorter postoperative drainage time [MD=−0.19, 95%CI (−0.35, −0.03), P=0.02], and lower overall complication rate [OR=0.55, 95%CI (0.31, 0.98), P=0.04]. Conclusion Lung subsegmentectomy can achieve similar efficacy as segmentectomy and has a lower overall postoperative complication rate. In terms of safety, lung subsegmentectomy can achieve a margin range close to that of segmentectomy. When performing uniportal thoracoscopic surgery, lung subsegmentectomy has advantages over segmentectomy in terms of intraoperative blood loss, postoperative hospital stay, and drainage time.

Objective To evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE)followed by hepatic arterial infusion chemotherapy(HAIC)combined with TKI drugs and PD-1 inhibitors as the first-line treatment for advanced hepatocellular carcinoma(HCC).Methods We retrospectively analyzed the data of 70 patients with advanced HCC treated in the Department of Oncology of Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine between July,2020 and June,2023.23 of the patients received TACE combined with HAIC and TKI(TACE+HAIC+TKI group)and 47 received TACE combined with HAIC,PD-1 inhibitors and TKI(TACE+HAIC+PD-1+TKI group).The clinical characteristics,laboratory test results,efficacy,outcomes and adverse events of the patients were compared between the two groups.Results The TACE+HAIC+TKI and TACE+HAIC+PD-1+TKI groups had significantly different objective remission rates(ORR;60.87%vs 36.17%,P=0.031),comparable disease control rates(95.65%vs 93.62%,P=0.068),and different median progression-free survival(PFS)time(10.2 vs 11.8 months,P=0.003)and median overall survival(OS)time(15.7 vs 19.5 months,P=0.035).After propensity score matching(PSM),the median PFS and OS time of the two groups was 10.1 vs 14.5 months(P=0.024)and 14.2 vs 21.2 months(P=0.221),respectively.The 1-year PFS rates of the 2 groups were 24.0%vs 52.2%,and the 1-,2-and 3-year OS rates were 72.3%vs 93.1%,23.9%vs 63.8%,and 23.9%vs 36.5%,respectively.The incidence of proteinuria was significantly higher in TACE+HAIC+PD-1+TKI group than in TACE+HAIC+TKI group(21.28%vs 0,P=0.025),but the incidences of grade 3-4 treatment-related adverse events were all similar between the two groups.Conclusion The first-line treatment with TACE+HAIC+PD-1+TKI is safe and effective for advanced HCC and can significantly prolong the survival of the patients.

Objective To evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE)followed by hepatic arterial infusion chemotherapy(HAIC)combined with TKI drugs and PD-1 inhibitors as the first-line treatment for advanced hepatocellular carcinoma(HCC).Methods We retrospectively analyzed the data of 70 patients with advanced HCC treated in the Department of Oncology of Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine between July,2020 and June,2023.23 of the patients received TACE combined with HAIC and TKI(TACE+HAIC+TKI group)and 47 received TACE combined with HAIC,PD-1 inhibitors and TKI(TACE+HAIC+PD-1+TKI group).The clinical characteristics,laboratory test results,efficacy,outcomes and adverse events of the patients were compared between the two groups.Results The TACE+HAIC+TKI and TACE+HAIC+PD-1+TKI groups had significantly different objective remission rates(ORR;60.87%vs 36.17%,P=0.031),comparable disease control rates(95.65%vs 93.62%,P=0.068),and different median progression-free survival(PFS)time(10.2 vs 11.8 months,P=0.003)and median overall survival(OS)time(15.7 vs 19.5 months,P=0.035).After propensity score matching(PSM),the median PFS and OS time of the two groups was 10.1 vs 14.5 months(P=0.024)and 14.2 vs 21.2 months(P=0.221),respectively.The 1-year PFS rates of the 2 groups were 24.0%vs 52.2%,and the 1-,2-and 3-year OS rates were 72.3%vs 93.1%,23.9%vs 63.8%,and 23.9%vs 36.5%,respectively.The incidence of proteinuria was significantly higher in TACE+HAIC+PD-1+TKI group than in TACE+HAIC+TKI group(21.28%vs 0,P=0.025),but the incidences of grade 3-4 treatment-related adverse events were all similar between the two groups.Conclusion The first-line treatment with TACE+HAIC+PD-1+TKI is safe and effective for advanced HCC and can significantly prolong the survival of the patients.

Extracellular vesicles (EVs) are tiny biological nanovesicles ranging from approximately 30-1000 nm in diameter that are released into the extracellular matrix of most cell types and in biofluids. The classification of EVs includes exosomes, microvesicles, and apoptotic bodies, dependent on various factors such as size, markers, and biogenesis pathways. The transition of EV relevance from that of being assumed as a trash bag to be a key player in critical physiological and pathological conditions has been revolutionary in many ways. EVs have been recently revealed to play a crucial role in stem cell biology and cancer progression via intercellular communication, contributing to organ development and the progression of cancer. This review focuses on the significant research progress made so far in the role of the crosstalk between EVs and stem cells and their niche, and cellular communication among different germ layers in developmental biology. In addition, it discusses the role of EVs in cancer progression and their application as therapeutic agents or drug delivery vehicles. All such discoveries have been facilitated by tremendous technological advancements in EV-associated research, especially the microfluidics systems. Their pros and cons in the context of characterization of EVs are also extensively discussed in this review. This review also deliberates the role of EVs in normal cell processes and disease conditions, and their application as a diagnostic and therapeutic tool. Finally, we propose future perspectives for EV-related research in stem cell and cancer biology.
Biomarkers/metabolism* ; Cell-Derived Microparticles/metabolism* ; Exosomes ; Extracellular Vesicles/metabolism* ; Humans ; Neoplasms/metabolism*

Objective:To evaluate the clinical efficacy of microneedle radiofrequency in the treatment of moderate acne vulgaris.Methods:From August 2018 to August 2020, 393 patients (192 males and 201 females, aged 15-38 years) with moderate acne were enrolled in the Department of Dermatology, the First Affiliated Hospital of Shantou University Medical College and Shantou Chaonan Minsheng Hospital, including 201 patients in experimental group and 192 patients in control group. In the experimental group, microneedle radiofrequency therapy was used once every 2 weeks for 3 times in total. The control group adopted the fire needle, once every 2 weeks, a total of 3 times. The efficacy of both groups was evaluated at week 8.Results:A total of 378 patients were actually completed: 196 patients in the experimental group, and 182 patients in the control group. At the eighth week of follow-up, the total effective rate was 81.12% in the experimental group and 70.43% in the control group. The efficacy of the two groups was statistically different (χ 2=4.42, P<0.05). Conclusions:The efficacy of microneedle radiofrequency therapy in the treatment of moderate acne vulgaris is better than that of fire needle, with good tolerance, short recovery period, few adverse reactions and high compliance, which has clinical promotion value.

Objective:To explore the clinical value of one-step CT angiography from deep vein of lower limbs to pulmonary artery in the direction of head and foot.Methods:Twenty-eight patients who presented Haikou Affiliated Hospital of Central South University Xiangya School of Medicine from January 2017 to June 2019 were collected. All patients who underwent one-step CT angiography of the deep veins of the lower extremities to the pulmonary artery were randomly divided into two groups, A or B, and scanned from the entrance of the thorax to 10 cm below the knee joint. Group A was foot-head direction group with delayed time scanning according to empirical method. Group B was the head-foot direction group with a single point triggered automatic tracing scan at the level of the main pulmonary artery trunk. The independent sample t-test was used to compare the scan time, dose length product (DLP), and mean CT value of enhancement of the pulmonary artery opening between the two groups. Results:The average scanning time of the foot-head scanning group was (36.4±1.2)s, the average DLP was (684.4±37.8) mGy·cm, and the average enhanced CT value of pulmonary artery image was (181.3±15.5) HU. The average scanning time of the head foot scanning group was (16.4±0.3) s, the average DLP was (441.8±34.4) mGy·cm, and the average enhanced CT value of the pulmonary artery image was (257.9±24.5) HU. Scanning time, mean DLP, and pulmonary artery level enhancement values were significantly different between the two groups ( t=17.92, 4.71, 2.44, P<0.05). Conclusions:The clinical value of one-step CT angiography from deep vein of lower limbs to pulmonary artery in the head-foot direction is significantly better than that in the head-foot direction. It can significantly shorten the scanning time, reduce the radiation dose, and increase the enhancement value of pulmonary artery to improve the detection of pulmonary embolism.

Objective:To investigate the values of CT angiography (CTA) and color Doppler ultrasound in the diagnosis and etiological screening of varicocele (VC).Methods:Ninety-seven patients with VC diagnosed by the Department of Urology, Central South University Xiangya School of Medicine Affiliated Haikou Hospital from May 2016 to December 2017 were retrospectively included. The CTA and color Doppler ultrasonographic data of 194 spermatic veins (including 116 varicocele veins) were analyzed. Paired t test was used to compare the mean diameter of spermatic veins at the root of scrotum measured by CTA and color Doppler ultrasound. McNemar test was used to compare the sensitivity and specificity of CTA and color Doppler examination for VC, and χ 2 or Fisher exact probability was used to compare the detection rate of CTA and color Doppler examination in screening the etiology of VC. Results:The average diameters of scrotal root of spermatic veins by CTA and color Doppler ultrasonography were (2.9±0.6) and (3.0±0.6) mm for VC cases, with no significant difference found( t=0.885, P=0.381). According to the diagnostic VC standard of color Doppler ultrasound (diameter>2 mm), no significant difference was found between CTA and color Doppler ultrasound in the sensitivity [95.69%(111/116) vs. 100%(116/116)] and specificity [100%(78/78) vs. 100%(78/78)] in the diagnosis of VC. The etiological detection rate of CTA in 97 patients with VC was significantly higher than that of color Doppler ultrasound ( P<0.05). Conclusions:Both CTA and color Doppler ultrasound have high sensitivity and specificity in the diagnosis of VC. CTA has a higher etiological detection rate in etiological screening of VC than color Doppler ultrasound.

OBJECTIVES: To explore the value of three-dimensional fast gradient echo sequence (3D-GRE) in observation of the craniocervical junctional ligament. METHODS: A total of 21 healthy volunteers underwent 3D-GRE imaging. The imaging data was imported into the post-processing workstation. The structures of the ligaments in the craniocervical junctional area were observed and evaluated by multiplanar reconstruction technique. RESULTS: The features of ligaments in the craniocervical junction were shown clearly for all the 21 cases of volunteers. The scan time was 267-294 s. After the treatment with the three-dimensional reconstruction technique, the signal characteristics and the running structure of the transverse ligament, the alar ligament, the serrated ligament and the lamina could be effectively displayed. CONCLUSIONS The 3D-GRE can evaluate the three-dimensional data of craniocervical junctional ligament in a short period of time. Post-processing reconstruction technique can clearly evaluate the structure characteristics of each ligament, which can lay a foundation for further application in craniocerebral trauma patients.
Diagnostic Imaging ; Humans ; Imaging, Three-Dimensional ; Ligaments, Articular/diagnostic imaging* ; Magnetic Resonance Imaging

Objective To analyze the changes of radioactivity of the marginal zone of hepatic alveolar echinococcosis (HAE) before and after the treatment with albendazole liposomes,and to explore the value of 18F-fluorodeoxyglucose (FDG) PET/CT imaging in therapeutic response.Methods From July 2011 to July 2015,37 patients (21 males,16 females;average age (53±12) years) with HAE were selected and underwent 18F-FDG PET/CT imaging before routine medication with albendazole liposomes (10 mg · d-1 · kg-1),and the maximum standardized uptake value (SUVmax) of the margin of lesions was calculated.PET/CT imaging was performed again 6 months later to measure the SUVmax of the marginal lesions.Two-sample t test was used to analyze the data.Results In 37 patients with HAE,SUVmax before treatment was 4.88± 1.86,which was higher than that of 24 patients with reduced lesion size after treatment (3.63± 1.38;t =5.24,P＜ 0.001).Conclusion 18F-FDG PET/CT is useful for evaluating the radioactivity of marginal zone of HAE before and after the treatment with albendazole liposomes,and SUVmax of the marginal zone could be valuable for therapeutic response evaluation.