Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Objective:To explore the effect of family empowerment model on the improvement of swallowing care ability and care preparedness of primary caregivers of first-episode stroke dysphagia patients, further to explore its impact on patients′s wallowing function and life quality.Methods:This study was a randomized controlled study. From January 2021 to December 2022, 80 main caregivers of patients with dysphagia caused by manual stroke admitted to the Department of Acupuncture and Moxibustion, Shenzhen Hospital of Traditional Chinese Medicine were selected as the research objects, and 40 cases in the control group and 40 cases in the observation group were selected by random number table method. The control group were treated with conventional nursing care of first-episode stroke dysphagia patients in the acupuncture and moxibustion Department. On the basis of the conventional care in the control group, the observation group were treated with family empowerment model intervention for 14 days and was followed up for 28 days. Primary caregivers′ swallowing care ability, Caregiver Preparedness Scale (CPS), patients′ swallowing function rate, Swallowing Related Quality of Life (SWALQOL) were used to evaluate the effects before intervention and at the end of intervention.Results:There were 18 males and 19 females primary caregivers in the control group, aged (55.61 ± 7.43) years old. There were 18 males and 21 females primary caregivers in the observation group, aged (58.23 ± 8.22) years old. The swallowing care ability score showed a statistically significant difference between the observation group (143.47 ± 3.96) and the control group (107.74 ± 1.43) ( t=-26.76, P<0.05). After intervention, the caregiver preparedness scale was (26.11 ± 3.81) in the observation group, and (18.35 ± 4.54) in the control group, and the difference was statistically significant ( t=-4.11, P<0.05).The patients′ swallowing function rate and SWALQOL score were respectively 97.44% (38/39) and (91.41 ± 8.08) points in the observation group, and 72.97% (27/37) and (80.33 ± 4.21) points in the control group, and the difference was both statistically significant ( χ2=10.76, t=-2.54, both P<0.05). Conclusions:The implementation of family empowerment model could enhance the swallowing care ability and care preparedness of primary caregivers of the first-episode stroke dysphagia patients, which could further improve patients′ swallowing function and life quality.

Objective To explore the enrichment method of the crude alkaloid of Zanthoxylum nitidum(Roxb.)DC.(Z.nitidum),which can inhibit the proliferative activity of human erythroid leukemia cells(HEL cells)in vitro,and to provide a scientific basis for the antitumor activity of Z.nitidum.Methods Z.nitidum was extracted using different concentrations of ethanol(60%,70%,80%,90%,and 100%)to determine the optimum extraction conditions according to the highest extraction rate.Static and dynamic adsorption determined the adsorption capacity of different macroporous resins(HPD 100,XDA-5,D101,HPD 722,HPD 400)on the ethanol extracts from Z.nitidum.The effects of crude alkaloids on the proliferation activity of HEL cells in each group were studied by the MTT method.Results Z.nitidum was extracted from 60%,70%,80%,90%,and 100%ethanol,and the extract with 60%ethanol concentration had the highest yield(11.937±0.002)%.Static and dynamic adsorption experiments showed that the adsorption capacity of the above five kinds of macroporous resins was 1∶500(extract of Z.nitidum∶macroporous resin).The crude alkaloids enriched by different macroporous resins have different effects on the proliferation activity of HEL cells.The inhibition rates(%)at a concentration of 80 μg·mL-1 of Z.nitidum were(59.62±3.46)%(XDA-5),(55.81±5.16)%(HPD 100),(59.33±1.33)%(D101),(79.63±1.02)%(HPD 722),and(83.97±0.38)%(HPD 400),respectively.HPD 400 macroporous resin-enriched crude alkaloids inhibited the proliferation of HEL cells most significantly(P<0.01).Conclusion The process of enriching the crude alkaloids of Z.nitidum using macroporous resin was simple and feasible,and the crude alkaloids enriched by HPD 400 showed significant inhibitory effects on HEL cells with good anti-leukemic activity.

OBJECTIVES: Pelvic floor sensory training is commonly used in clinical practice for the treatment of stress urinary incontinence (SUI); however, there is a lack of comparative studies evaluating pelvic floor sensation between women with SUI and healthy controls. Additionally, normative data for two-point discrimination thresholds in the female pelvic floor region remain scarce. This study aims to compare the results of 4 sensory tests in the pelvic floor region between women with mild SUI and healthy women, in order to provide reference values for two-point discrimination thresholds in this area. METHODS: From April 1 to October 30, 2023, 108 healthy women [(32.5±3.6) years] and 90 women with mild SUI [(32.9±3.3) years] were recruited from the Third Xiangya Hospital, Central South University. Participants underwent 4 sensory tests in the pelvic floor region: Two-dot discrimination, weight perception, shape recognition, and 9-grid localization. The results were compared between the 2 groups. RESULTS: Compared with healthy women, those with mild SUI had lower sensitivity and higher thresholds in 2-dot discrimination tests in the pelvic floor region (all P<0.001). No significant differences were found between groups in weight perception, shape recognition, or grid localization tests (P>0.05). CONCLUSIONS Women with mild stress urinary incontinence have impaired two-point discrimination ability in the pelvic floor region.
Humans ; Female ; Urinary Incontinence, Stress/physiopathology* ; Pelvic Floor/physiopathology* ; Adult ; Sensory Thresholds/physiology*

To summarize the clinical manifestations of a case with 46, XY sex development disorder caused by myelin regulatory factor(MYRF) gene mutation and review the literature to deepen the specialists′ understanding of the clinical disease spectrum resulting from MYRF gene variations. The child had a female phenotype with mild masculinity, chromosome 46, XY, sex-determining region of Y gene(SRY gene) positive, laboratory tests were consistent with primary hypogonadism, ultrasound did not detect the gonads, but the residual reproductive tract was visible, and echocardiography suggested coarctation of the aorta, MYRF gene c. 2518C>T(p.R840*) heterozygous variant. The father did not carry this variant. The mother was untraceable, and genetic testing had not been completed. It was analyzed as pathogenic variation according to American College of Medical Genetics and Genomics(ACMG) guidelines. Sixteen cases of disorders of sex development caused by MYRF gene variation reported from 2018 to 2021 were reviewed, MYRF gene variants, 46, XY, and 46, XX individuals can be pathogenic, can affect the gonad and reproductive tract at the same time, and can also affect multiple systems. In this case, the patient presents with 46, XY sex development disorder due to MYRF gene mutation, accompanied by rare cardiovascular complications. When encountering 46, XY primary hypogonadism without well-developed Müllerian duct structures, this condition should be considered. Following confirmation, a comprehensive assessment of multi-organ function is necessary.

Objective:To report embryonic testicular regression syndrome(ETRS) caused by DHX37 heterozygous variant for the first time in China and summarize the clinical manifestations of ETRS as to improve the understanding of doctors for this disease.Methods:The clinical data and whole exome sequencing results of five cases of ETRS from Shenzhen Children′s Hospital were collected. The reported cases of DHX37 heterozygous variant were reviewed.Results:Five patients with ETRS visited the doctors at the age of 2 months to 5 years and 5 months. Three patients raised as males came to hospital due to virilition and 2 female patients visited a doctor due to clitoral hypertrophy. No uterus was detected by ultrasound in all patients. The gonadal pathologies from 4 cases displayed no testicular tissue or gonadal dysgenesis, complicated with gonadoblastoma in one case. The genetic testing revealed that the heterozygous variant(c.923G>A, p. R308Q) in DHX37 was found in 2 cases, without variant in other 3 cases. According to the review, ETRS and 46, XY gonadal dysgenesis due to DHX37 herozygous variant was firstly reported in 2019. A total of 40 cases, including 21 cases of ETRS, presented with the virilition or female phenotype, with the disappearance of testicular tissue as the main pathologies. There is no report in China.Conclusion:The article summarized the clinical manifestations and whole exome sequencing results of 5 patients with ETRS, among which two cases were caused by DHX37 variants and one was complicated with gonadoblastoma.

Objective To investigate the effect of incremental load training on AMP-activated protein kinase (AMPK) phosphorylation in skeletal muscle satellite cells of aged mice. Methods Experimental mice were divided into 3 groups: young control group (YC group, n=12), old control group (OC group, n=12) and old training group (OT group, n=12). The mice in OT group received incremental load training, and CD45-/CD31-/Sca1-/VCAM (CD106) + cells were isolated by flow cytometry sorting. Desmin, Myod myogenic staining and myogenic differentiation culture were used for identification of muscle satellite cells, and the p-AMPK level of muscle satellite cells was detected by immunohistochemistry combined with Western blotting method. Results The expression levels of AMPK and p-AMPK in skeletal muscle satellite cells in YC group were significantly higher than those in OC group (P<0.05). AMPK expression in OT group and OC group did not change significantly (P>0.05), while p-AMPK expression level in OT group was significant higher than that in OC group (P<0.05). Conclusions Incremental load training can promote AMPK phosphorylation of skeletal muscle satellite cells in aged mice, and improve energy metabolism of skeletal muscle in aged mice.

Objective:To explore the application value of BOPPPS teaching mode in the course of Medical Literature Retrieval. Methods:We selected 144 students from four classes of Chinese medicine in our school of Batch 2018 as the research objects, set 72 students from Class 1 and 3 as the experimental group, taking the BOPPPS teaching mode, and set 72 students in Class 2 and 4 as the control group, using traditional teaching mode. After the teaching activities were completed, the teaching effect, teaching satisfaction, and evaluation of the teaching results of the two groups of students were compared through basic theoretical examinations, database operation and questionnaire surveys. SPSS 21.0 software was performed for data analysis.Results:The database assessment scores of the experimental group and the control group were (87.82 ± 9.24) points and (82.50 ± 6.18) points, respectively, with statistical differences between the two groups ( P=0.001, P<0.05). The questionnaire survey showed that the feedback of the experimental group in database use, stimulating learning interest and teaching satisfaction were better than that of the control group, with statistical differences ( P<0.05). Conclusion:The BOPPPS teaching mode helps to stimulate students' interest in learning, improve learning efficiency, and ultimately improve the quality of teaching.

[Abstract] Objective: To investigate the effect of miR-3195 on the proliferation of laryngeal carcinoma Hep-2 cells and its molecular mechanism. Methods: From January 2008 to August 2012, the laryngeal cancer tissues and their corresponding paracancerous tissues from 29 patients with laryngeal cancer who were admitted to the Department of Otorhinolaryngology, Chenzhou First People's Hospital Affiliated to teaching hospital of University of South China were selected for this study. qPCR was used to detect the expression of miR-3195 in laryngeal carcinoma and the paracancerous tissues; Hep-2 cell line with stable and high expression of miR-3195 was constructed. The proliferation of miR-3195 over-expressed Hep-2 cells and the control cells was observed by MTT method. A nude mouse xenograft model was established to observe the proliferation of miR-3195 overexpressed Hep-2 cells in nude mice. Bioinformatics tools were used to predict the target gene of miR-3195; the luciferase vector of TBX1 3'UTR was constructed, and its luciferase activity was examined with dual luciferase detection system; Western blotting was used to detect the TBX1 protein expression in miR-3195 over-expressed cells and control cells. Results: The expression of miR-3195 in laryngeal carcinoma tissues was significantly lower than that in paracancerous tissues (P<0.01); miR-3195 up-regulation could inhibit the proliferation of Hep-2 cells (P<0.01) and significantly inhibit the growth of transplanted tumors in nude mice (P<0.05); The results of the Dual luciferase reporter gene assay indicated that miR-3195 might targetedly bind to TBX1 (P<0.05), and Western blotting proved that miR-3195 could inhibit the expression of TBX1 protein (P<0.05). Conclusion: miR-3195 has a significant inhibitory effect on the proliferation of Hep-2 cells, and its molecular mechanism may be related to the negative regulation of TBX1 expression.

Objective:To detect the levels of cytokines in peripheral blood of patients with chronic immune thrombocytopenia (ITP) and analyze their significance in the clinical prognosis of children with chronic ITP.Methods:Thirty patients with chronic ITP who were treated in the Department of Pediatrics, the First Affiliated Hospital of Xinxiang Medical Univercity from October 2015 to October 2018 were followed and enrolled in the experimental group and 40 healthy children in the same hospital were enrolled in the healthy control group.The levels of interleukin-2(IL-2), interferon-γ(IFN-γ), tumor necrosis factor(TNF), interleukin-4(IL-4), interleukin-6(IL-6), interleukin-10(IL-10) and interleukin-17A(IL-17A) in the experimental group and the healthy control group were detected by flow cytometry (CBA). The relationship between cytokines and prognosis of children with chronic ITP were analyzed.Results:Thirty patients with ITP were enrolled. The expressions of IL-2 and IL-17A in the experimental group before treatment were (7.86±3.90) ng/L and (10.45±12.35) ng/L, while those of IL-2 and IL-17A in the healthy control group were (3.11±2.41) ng/L and (2.97±7.04) ng/L. The levels of IL-2 and IL-17A in the experimental group were significantly higher than those in the healthy control group, and the differences were statistically significant ( t=-7.123, -5.582, all P<0.01). The expressions of IL-4 and IL-10 in the experimental group before treatment were (0.38±0.25) ng/L and (1.80±1.25) ng/L, while those of IL-4 and IL-10 in the healthy control group were (3.08±0.26) ng/L and (4.55±3.44) ng/L. The levels of IL-4 and IL-10 in the experimental group were significantly lower than those in the healthy control group, and the differences were statistically significant ( t=8.400, 5.653, all P<0.01). The expressions of IL-6, TNF and IFN-γ in the experimental group before treatment were (7.30±9.16) ng/L, (4.85±7.60) ng/L and (7.68±20.41) ng/L, while those of IL-6, TNF and IFN-γ in the healthy control group were (5.44±4.18) ng/L, (1.97±0.37) ng/L, (4.81±17.71) ng/L. There was no significant difference between the two groups ( P>0.05), and no significant difference in the levels of cytokines between the patients with chronic ITP before and 12 months after treatment ( P>0.05). Conclusions:The changes of T lymphocyte related cytokines are closely related to the pathogenesis and development of chronic ITP in children. There may be persistent immune dysfunction in children with chronic ITP. Dynamic monitoring of cytokines IL-2, IL-4, IL-10, IL-17A, especially IL-17A, is helpful to judge the prognosis of ITP in children, and may be of guiding significance in evaluating clinical prognosis.