Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE ^-/- mice, primarily by transepithelial absorption via M cells in Peyer's patches and subsequent translocation via macrophages through the lymphatic system. Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis. Moreover, oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects. Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids, either alone or in combination with existing drugs, offering a promising approach for precision therapy of atherosclerotic diseases.

Objective:To survey the availability status of pharmaceutical and medical device for venous thromboembolism (VTE) prevention and the awareness among healthcare workers in community health service centers in Shanghai.Methods:This cross-sectional study was conducted by online questionnaire survey among doctors, nurses, and pharmacists from 20 community health service centers in Shanghai from June 2023 to April 2024. The survey covered participants′ demographic information, VTE prevention and management practices at their centers, the knowledge of VTE prevention, and related training or education. The assessment of VTE prevention and management status was completed by department heads of pharmacy, medical equipment, nursing, and inpatient units.Results:A total of 864 healthcare professionals participated in the survey, including 587(67.9%) doctors, 246(28.5%) nurses, and 31(3.6%) pharmacists, and 675(78.1%) were females. Among the 20 centers, 19 stocked VTE prevention medications, while only 8 had VTE prevention devices. Of the 864 participants, 145(16.8%) reported conducting VTE risk assessments for all patients, and 279(32.3%) correctly identified VTE as comprising deep vein thrombosis and pulmonary embolism. While 664(76.9%) believed that VTE risk assessment for hospitalized patients was necessary, only 11(1.3%) were familiar with and routinely used VTE risk assessment tools. Over 85% recognized advanced age, body mass index (BMI)>30 kg/m2, recent major surgery, prolonged immobilization, stroke, and varicose veins as VTE risk factors. A majority (837(96.9%)) agreed that bleeding risk assessment should precede pharmacological VTE prevention, and 549(63.5%) preferred oral antiplatelet agents as the first choice. Convenience (730(84.5%)) and safety (719(83.2%)) were key considerations in drug selection, while 710(82.2%) expressed concern about bleeding risks during medication. Only 258(29.9%) had received VTE-related training.Conclusions:Community health service centers in Shanghai face shortages in VTE prevention devices and medications, and healthcare professionals′ awareness of VTE needs to be improved. Enhanced training and education on VTE prevention are warranted.

Objective:To analyze and summarize clinical phenotypic characteristics and genetic variations in patients with intellectual disability and pathogenic variations of the DYNC1H1 gene across 4 generations within a single family. Methods:Retrospective case analysis.Clinical data of a child with epilepsy and intellectual disability and her family members were collected from the Children′s Medical Center, Peking University First Hospital on December 2019.The child was followed up regularly.DNA was extracted from the peripheral blood of the child′s family members.Then whole-exome sequencing and Sanger sequencing were performed to identify the genetic variation type in the proband and her family members.The relationship between genotype and phenotype was further analyzed.Results:A total of 13 patients across 4 generations in the family had intellectual disability, and the proband also had drug-resistant epilepsy.The variation c. 13556C> A (p.A4519E) of the DYNC1H1 gene was confirmed by gene testing in 8 patients (no blood samples were obtained from the remaining patients). Conclusions:DYNC1H1 gene-related intellectual disability in most previously reported cases are caused by novel variations of this gene.In this study, a large family of 13 intellectual disability patients across 4 generations caused by a pathogenic mutation in the DYNC1H1 gene was summarized.The findings make precise genetic counseling possible for this family and provide a basis for further studies on the relationship between the genotype and phenotype of the DYNC1H1 gene.

Objective:To analyze and summarize clinical phenotypic characteristics and genetic variations in patients with intellectual disability and pathogenic variations of the DYNC1H1 gene across 4 generations within a single family. Methods:Retrospective case analysis.Clinical data of a child with epilepsy and intellectual disability and her family members were collected from the Children′s Medical Center, Peking University First Hospital on December 2019.The child was followed up regularly.DNA was extracted from the peripheral blood of the child′s family members.Then whole-exome sequencing and Sanger sequencing were performed to identify the genetic variation type in the proband and her family members.The relationship between genotype and phenotype was further analyzed.Results:A total of 13 patients across 4 generations in the family had intellectual disability, and the proband also had drug-resistant epilepsy.The variation c. 13556C> A (p.A4519E) of the DYNC1H1 gene was confirmed by gene testing in 8 patients (no blood samples were obtained from the remaining patients). Conclusions:DYNC1H1 gene-related intellectual disability in most previously reported cases are caused by novel variations of this gene.In this study, a large family of 13 intellectual disability patients across 4 generations caused by a pathogenic mutation in the DYNC1H1 gene was summarized.The findings make precise genetic counseling possible for this family and provide a basis for further studies on the relationship between the genotype and phenotype of the DYNC1H1 gene.

Objective:To survey the availability status of pharmaceutical and medical device for venous thromboembolism (VTE) prevention and the awareness among healthcare workers in community health service centers in Shanghai.Methods:This cross-sectional study was conducted by online questionnaire survey among doctors, nurses, and pharmacists from 20 community health service centers in Shanghai from June 2023 to April 2024. The survey covered participants′ demographic information, VTE prevention and management practices at their centers, the knowledge of VTE prevention, and related training or education. The assessment of VTE prevention and management status was completed by department heads of pharmacy, medical equipment, nursing, and inpatient units.Results:A total of 864 healthcare professionals participated in the survey, including 587(67.9%) doctors, 246(28.5%) nurses, and 31(3.6%) pharmacists, and 675(78.1%) were females. Among the 20 centers, 19 stocked VTE prevention medications, while only 8 had VTE prevention devices. Of the 864 participants, 145(16.8%) reported conducting VTE risk assessments for all patients, and 279(32.3%) correctly identified VTE as comprising deep vein thrombosis and pulmonary embolism. While 664(76.9%) believed that VTE risk assessment for hospitalized patients was necessary, only 11(1.3%) were familiar with and routinely used VTE risk assessment tools. Over 85% recognized advanced age, body mass index (BMI)>30 kg/m2, recent major surgery, prolonged immobilization, stroke, and varicose veins as VTE risk factors. A majority (837(96.9%)) agreed that bleeding risk assessment should precede pharmacological VTE prevention, and 549(63.5%) preferred oral antiplatelet agents as the first choice. Convenience (730(84.5%)) and safety (719(83.2%)) were key considerations in drug selection, while 710(82.2%) expressed concern about bleeding risks during medication. Only 258(29.9%) had received VTE-related training.Conclusions:Community health service centers in Shanghai face shortages in VTE prevention devices and medications, and healthcare professionals′ awareness of VTE needs to be improved. Enhanced training and education on VTE prevention are warranted.

Objective To compare the effectiveness of Defocus Incorporated Multiple Segments (DIMS) and High Aspheric Lenslet (HAL) defocus lenses in controlling myopia. Methods A total of 214 children and adolescents who were fitted with defocus lenses (DIMS or HAL) in our hospital from January to June 2023 were selected, including 100 cases in DIMS group and 114 cases in the HAL group. Changes in parameters such as spherical lens power, cylindrical lens power, spherical equivalent (SE), corneal curvature (K), axial length (AL), binocular accommodative response (BCC), positive/negative relative accommodation (PRA/NRA), distance/near latent phoria (DLP/NLP), and accommodative convergence to accommodation ratio (AC/A) were compared between the two groups before wearing and after wearing the lenses for 6 months, and the effectiveness of myopia control between DIMS and HAL was further compared. Results After wearing the lenses (DIMS or HAL) for 6 months, the average increase in axial length was (0.09±0.14) mm, the average increase in spherical lens power was (-0.11±0.23) D, the average increase in astigmatism was (-0.07±0.16) DC, and the average increase in spherical equivalent was (-0.15±0.24) D, with statistically significant differences observed for all these changes (t=9.24, -7.27, -6.60, -9.03, respectively, P < 0.001). Compared with parameters before wearing the lenses, statistically significant differences were noted after wearing for 6 months in spherical lens power, cylindrical lens power, SE, BCC, PRA, DLP, average K, and AL (P≤0.001), except for NRA (t=-0.12, P>0.05), NLP (t=-0.28, P>0.05), and AC/A (t=0.33, P>0.05). The differences in parameters between the two groups after wearing the lenses for 6 months showed a statistically significant difference only in the AL difference (t=4.38, P≤0.001), with no statistically significant differences observed for other parameter differences (P>0.05). Conclusion Wearing defocus lenses has a positive effect on controlling myopia, delaying axial length elongation, and maintaining binocular visual function balance.

Objective To explore the strategy of intrathoracic anastomosis in patients with esophageal squamous cell carcinoma when the proximal esophagus is dilated to different degrees and explore its mechanism. Methods We retrospectively reviewed the clinical data of patients who underwent esophagectomy between 2014 and 2017 in West China Hospital. The patients were divided into two groups including a significant dilatation group with inner mucosal phase diameter (IMPD)≥17.9 mm and a non-significant dilatation group with IMPD<17.9 mm. And the patients were divided into two groups (a layered manual anastomosis group and a stapled anastomosis group) according to anastomosis method and propensity score matching was applied to adjust for potential confounders. Results We finally included 654 patients. There were 206 patients with 158 males and 48 females at average age of 62.21±7.72 years in the layerd manual analstomosis group and 448 patietns with 377 males and 71 females at average age of 62.57±8.42 years in the stapled anastomosis group. We also used Masson trichrome staining to assess the collagen fiber content in the esophagus. Compared with layered manual anastomosis, the incidence of anastomotic leakage was higher in the significant dilatation group than that in the stapled anastomosis group (original cohort: 3.8% vs. 10.7%, P=0.093; propensity score-matched cohort: 1.4% vs. 15.3%, P=0.004). And there was no significant difference in anastomotic leakage b etween layered manual anastomosis and stapled anastomosis in the non-significant dilatation group (original cohort: 4.7% vs. 4.2%, P=0.830; propensity score-matched cohort: 4.8% vs. 4.0%, P=0.206). Moreover, the average collagen fiber area ratio was significantly lower in the significant dilation group than that in the non-significant dilatation group (P=0.045). Conclusion There is a significant reduction in collagen fibers in the proximal esophageal wall tissue of esophageal squamous cell carcinoma patients with a IMPD≥17.9 mm. Intrathoracic layered manual anastomosis effectively reduces postoperative anastomotic leakage in these patients.

Based on the virtual simulation of "digital embryo" in the digital teaching platform for medical morphology, this study constructs the course resources of human embryology by integrating the contents of the course, recording micro-videos, formulating course guides, and analyzing clinical cases, then implements the blended teaching model of pre-class preview, in-class discussion, and after-class expansion, and establishes a course evaluation system combining formative assessment and end-of-course assessment. Comparison of assessment scores and satisfaction questionnaire between traditional off-line teaching and blended teaching showed a significant improvement in total score, and more than 5% of the students reported a significant reduction in the difficulty of the course, while the degree of satisfaction with the course was increased by 11%. This suggests that the establishment of the blended teaching model of human embryology meets the requirements for personalized and diversified learning among students, realizes the diversity of teaching methods and teaching evaluation, and improves the quality of teaching.

Objective    To compare the surgical efficacy of Da Vinci robot-assisted minimally invasive esophagectomy (RAMIE) and video-assisted minimally invasive esophagectomy (VAMIE) on esophageal cancer. Methods    Online databases including PubMed, the Cochrane Library, Medline, EMbase and CNKI from inception to 31, December 2019 were searched by two researchers independently to collect the literature comparing the clinical efficacy of RAMIE and VAMIE on esophageal cancer. Newcastle-Ottawa Scale was used to assess quality of the literature. The meta-analysis was performed by RevMan 5.3. Results    A total of 14 studies with 1 160 patients were enrolled in the final study, and 12 studies were of high quality. RAMIE did not significantly prolong total operative time (P=0.20). No statistical difference was observed in the thoracic surgical time through the McKeown surgical approach (MD=3.35, 95%CI –3.93 to 10.62, P=0.37) or in surgical blood loss between RAMIE and VAMIE (MD=–9.48, 95%CI –27.91 to 8.95, P=0.31). While the RAMIE could dissect more lymph nodes in total and more lymph nodes along the left recurrent laryngeal recurrent nerve (MD=2.24, 95%CI 1.09 to 3.39, P=0.000 1; MD=0.89, 95%CI 0.13 to 1.65, P=0.02) and had a lower incidence of vocal cord paralysis (RR=0.70, 95%CI 0.53 to 0.92, P=0.009). Conclusion    There is no statistical difference observed between RAMIE and VAMIE in surgical time and blood loss. RAMIE can harvest more lymph nodes than VAMIE, especially left laryngeal nerve lymph nodes. RAMIE shows a better performance in reducing the left laryngeal nerve injury and a lower rate of vocal cord paralysis compared with VAMIE.