Under the trend of increasing aging， integrated elderly care and medical services is an important measure to optimize the supply of elderly care services and promote the good death of the elderly. Using the cooperative production theory and the classical grounded theory， a qualitative analysis was conducted on 38 cases of elderly palliative care and 25 cases of hospital-based palliative care under the integrated elderly care and medical services model from a hospital in Nanning City using Nvivo 20.0 software. This paper found that the integrated elderly care and medical services mode emphasized the deep integration of medical and elderly care services by integrating resources and improving service efficiency， to achieve the basic experience of comprehensive health care for the elderly. The promotion of these experiences has a positive significance for building a multi-agent cooperative production system， strengthening personnel training， perfecting the performance distribution mechanism， and further promoting the development of the national palliative care pilot.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

The problems caused by proximal contact loss(PCL)of dental implants have been a mainstream research topic in recent years,and scholars are unanimously committed to analyzing their causes and related factors,aiming to identify solutions to the problems related to PCL.The effects of the anterior component of force(ACF),the lifelong re-molding of the adult craniofacial jaw and alveolar socket,and the osseointegration characteristics of dental implants are the main causes of PCL.On the one hand,the closing movement of the mandible causes the ACF of the tooth to move through the posterior molar cusp.Moreover,drifting between the upper and lower posterior teeth and mandibular anteri-or teeth can cause the anterior teeth of the upper and lower jaws to be displaced labially.On the other hand,reconstruc-tion of the jaw,alveolar socket and tooth root,the forward horizontal force of the masticatory muscles,the dynamic com-ponent of the jaw and the forward force generated by the oblique plane of the tooth cusp can cause the natural tooth to experience near-middle drift.Additionally,natural teeth can shift horizontally and vertically and rotate to accommodate remodeling of the stomatognathic system and maintain oral function.Nevertheless,the lack of a natural periodontal mem-brane during implant osseointegration,the lack of a physiological basis for near-medium drift,the small average degree of vertical motion and the integrated silence of dental implants without the overall drift characteristics of natural teeth increases the probability of PCL.The high incidence of PCL is clearly associated with the duration of prosthesis delivery and the mesial position;but it is also affected by the magnitude of the bite force,occlusion,the adjacent teeth,restora-tion design,implant location,jaw,and patient age and sex.PCL has shown a significant correlation with food impaction,but not a one-to-one correspondence,and did not meet the necessary and sufficient conditions.PCL is also associated with peri-implant lesions as well as dental caries.PCL prevention included informed consent,regular examinations,se-lection of retention options,point of contact enhancement,occlusal splints,and the application of multipurpose digital crowns.Management of the PCL includes adjacent contact point additions,orthodontic traction,and occlusal adjust-ment.Existing methods can solve the problem of food impaction in the short term with comprehensive intervention to seek stable,long-term effects.Symmetric and balanced considerations will expand the treatment of issues caused by PCL.

Objective:To explore the effects of hinokiol on the cell cyle and apoptosis of CNE1 nasopharyngeal carcinoma cells and the relevant molecular mechanism.Methods:The CNE1 cells were cultured in vitro and incubated with different concentrations of honokiol, and the cells were divided into blank control group, 10 μmol/L, 20 μmol/L and 40 μmol/L hinokiol treatment groups, and 10 μg/ml cisplatin group. Cell viability was determined by methylthiazolyldiphenyl- tetrazolium bromide (MTT) method, the cell cycle distribution was detected by flow cytometry, mitochondrial membrane potential was detected by mitochondrial membrane potential test kit, apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method, and the proteins expression of proliferating cell nuclear antigen (PCNA) and G 1/S specific cyclin D1 (cyclin D1) were detected by immunoblotting. RNA-Seq was conducted in the hinokiol-treated cells. The mRNA expression of yes-associated protein delta (YAP) was detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). The proteins expression of phosphor-YAP (p-YAP) and nuclear YAP were detected by immunoblotting, the nuclear distribution of YAP protein was detected by immunofluorescence in the cells with or without treated with the mammalian STE20-like kinase 1/2 (MST1/2) inhibitor (XMU-MP-1), hinokiol, and XMU-MP-1+hinokiol. Statistical analysis of the data was conducted using GraphPad Prism 8.0 software. Resluts Compared with the control group, the cell viablity of CNE1 cells, the levels of mitochondrial membrane potential, the proteins expression of PCNA and cyclin D1 in hinokiol treatment groups were markedly decreased (all P values<0.05), while the proportion of G 0/G 1 phase cells and the ratio of TUNEL-positive cells were significantly increased (both P values<0.05). Transcriptome analysis showed that differential genes were mainly enriched in Wnt signaling pathway, tumor necrosis factor pathway, and Hippo signaling pathway. The mRNA level of YAP and the protein expression of YAP in the nucleus were decreased and the level of p-YAP protein was increased in cells treated with hinokiol, which were significantly different from control group (all P values<0.05). Compared with the hinokiol group, XMU-MP-1+hinokiol groups showed the decrease of p-YAP protein expression (1.157±0.076 vs 0.479±0.038, t=37.120, P<0.05), the increase of YAP protein expression in the nucleus (0.143±0.012 vs 0.425±0.031, t=29.181, P<0.05), the reduced proportion of cells in G 0/G 1 phase [(72.494±3.309)% vs (58.747±2.865)%, t=17.265, P<0.05], and the decrease of apoptosis ratio [(53.158±3.376)% vs (29.621±2.713)%, t=28.584, P<0.05]. Conclusion:Hinokiol can arrest the cell cycle and induce the cell apoptosis of CNE1 cells via Hippo/YAP signaling pathway.

Objective To investigate the effect of teaching method using students as standardized patients on clinical practice teaching of neurology.Methods We randomly assigned 80 undergraduate majoring in clinical medicine into two groups:a control group where students were instructed with traditional clinical teaching methods,and an experimental group where students acted as standardized patients.Following the clinical placement,we administered an Objective Structured Clinical Exam-ination(OSCE)and a satisfaction survey to all participants.Results The experimental group performed significantly better than the control group in history taking and neurological examination in the OSCE(P＜0.05).The results of the questionnaire showed that the experimental group scored significantly higher than the control group in improving clinical thinking,stimulating learning interest,and improving communication skills(P＜0.05).Conclusion The teaching methods using student as standardized pa-tients in the process of clinical practice in neurology helps to improve the history taking and neurological physical examination skills of clinical students,yielding good educational outcomes.

Objective We tried to investigate the effects of human umbilical cord mesenchymal stem cell exosomes(hUCMSC-Exos)on the proliferation of human dermal papilla cells(HDPCs)and the mechanism of hUCMSC-Exos promoting hair growth.Methods HDPCs were isolated using two-step enzymatic method and cul-tured in vitro.Human umbilical cord mesenchymal stem cells(hUC-MSCs)were cultured.Cell culture supernatant was collected,and exosomes were isolated and extracted using high-speed centrifugation.Electron microscopy,particle size,and surface marker identification were performed on them.Dihydrotestosterone(DHT)induces HDPCs and establishment of an androgenic alopecia cell model.Co-culture hUCMSC-Exos with HDPCs,cell proliferation experiment(EdU)was used to detect the relative activity of induced HDPCs.Real-time qPCR was used to detect the expression level of alkaline phosphatase(ALP),and Western blot was used to detect β-catenin,Wnt10b,GSK-3β expression at the protein level.Results The obtained primary HDPCs,hUC-MSCs,and hUCMSC-Exos were all conformed to the characteristics of dermal papilla cells,mesenchymal stem cells,and exosomes.The num-ber of EdU positive cells significantly increased,and exosomes could effectively promote the proliferation of HDPCs(P<0.05),enhance the vitality of HDPCs and alleviate the damage caused by DHT(P<0.05).Real-time qPCR showed that exosomes could enhance the expression level of ALP gene(P<0.05)and hair follicle induction ability.Western Blot confirmation β-catenin,Wnt10b,GSK-3β were differences in expression at the protein level(P<0.05).Conclusions HUCMSC-Exos could promote DHT induced proliferation of HDPCs,enhance their hair follicle regeneration and repair ability,and its mechanism may be related to the activation of Wnt/β-catenin signaling pathway.

Objective To investigate the effect and mechanism of Rougan Huaxian particle on hepatic fibrosis.Methods SD rats were divided into normal group,model group,normal saline control group,Rougan Huaxian particle low,middle,high dose group,Rougan Huaxian particle middle dose+3-MA group.Liver fibrosis model was induced by intraperitoneal injection of CCl4.Rougan Huaxian particle was administered with low,middle and high dose(2.5 mg·kg-1,5 mg·kg-1,10 mg·kg-1)and 3-MA(15 mg·kg-1)respectively.The expression of miR-135a,FOXO1,PINK1,Parkin,LC3 II,Smad2,p-Smad2,TGF-β1,NF-κB p65,p-NF-κB p65,α-SMA,Collagen I,Collagen III,TNF-α and the content of ROS were detected by Real-time PCR,Western Blot and ELISA.Results The expression of miR-135a,α-SMA,Collagen I,Collagen III,p-Smad2,TGF-β1,p-NF-κB p65,TNF-α and ROS in model group were significantly up-regulated(P<0.05),and the expression of FOXO1,PINK1,Parkin,LC3 II were significantly down-regulated(P<0.05).The middle and high dose of Rougan Huaxian particle could significantly inhibit the expression of miR-135a,α-SMA,Collagen I,Collagen III,p-Smad2,TGF-β1,p-NF-κb p65,TNF-α and ROS,and up-regulate the expression of FOXO1,PINK1,Parkin,LC3 II(P<0.05).The expression of miR-135a,α-SMA,Collagen Ⅰ,Collagen Ⅲ,p-Smad2,TGF-β1,p-NF-κB p65 and TNF-α and the production of ROS were significantly inhibited in the medium and high dose groups.Up-regulated expression of FOXO1,PINK1,Parkin and LC3Ⅱ(P<0.05).The effect of Rougan Huaxian Particle in middle dose group was stronger than that in low dose group(P<0.05),and there was no significant difference between middle and high dose groups.Mitophagy inhibitor(3-MA)could significantly inhibit the efficacy of rougan Huaxian particle(P<0.05).Conclusion Ruugan Huaxian granules can inhibit liver fibrosis,and its mechanism is related to the inhibition of miR-135a expression,activation of FOXO1/PINK1 pathway,promotion of mitochondrial autophagy,inhibition of oxidative stress response,and inhibition of TGF-β1/Smad2 activation.

Aim To investigate whether SIRT6 overexpression inhibits angiotensin Ⅱ(Ang Ⅱ)-induced cardio-myocyte apoptosis by activating adenosine 5'-monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2/heme oxygenase-1(AMPK/Nrf2/HO-1)signaling pathway.Methods The experiment was divided into 4 groups:control group,AngⅡ group,Ang Ⅱ+SIRT6 group,Ang Ⅱ+empty vector(EV)group.The mRNA level of SIRT6 was detected by RT-PCR.The cell activity was measured by MTT assay.The cell apoptosis was analyzed by flow cy-tometry.SIRT6,cardiomyocyte apoptosis related proteins(Bax,cleaved Caspase-3,Bcl-2),DNA damage related pro-teins(γ-H2AX,p-ATM),AMPK/Nrf2/HO-1 signaling pathway related proteins(p-AMPK,Nrf2,HO-1)were measured by Western blot.The reactive oxygen species(ROS)content was determined by DCFH-DA staining.The changes of the above indexes among the groups were observed.Results Compared with control group,the mRNA and protein ex-pression levels of SIRT6 and cell activity were significantly decreased in Ang Ⅱ group.Apoptosis rate,the expressions of Bax,cleaved Caspase-3 were increased,and the expression of Bcl-2 was decreased.The expressions of γ-H2AX and p-ATM were increased,and the expressions of p-AMPK,Nrf2,HO-1 were decreased.The activity of ROS was increased(P＜0.01).Compared with Ang Ⅱ+EV group,the expression of SIRT6 and cell activity were significantly increased in Ang Ⅱ+SIRT6 group.Apoptosis rate,the expressions of Bax and cleaved Caspase-3 were decreased,and the expression of Bcl-2 was increased.The expressions of γ-H2AX and p-ATM were decreased,the expressions of p-AMPK,Nrf2,HO-1 were increased.The activity of ROS was decreased(P＜0.01).Conclusion SIRT6 overexpression inhibits Ang Ⅱ-induced cardiomyocyte apoptosis through activation of AMPK/Nrf2/HO-1 signaling pathway.

Gastric cancer is one of the most common malignant tumors worldwide,with high morbidity and mortality rates.This malignancy poses a grave threat to human life and health.Its early onset symptoms are not typical,and many patients are diagnosed in the middle and late stages;multidisciplinary comprehensive treatment remains the primary treatment for patients with advanced and unresectable gastric cancer.Comprehensive surgery is typically performed for patients with gastric cancer who are eligible for surgery.Preoperative arterial infu-sion chemotherapy is gradually receiving attention as a novel treatment method.Compared with traditional chemotherapy,it has the ad-vantages of higher efficiency,fewer side effects,and a higher surgical resection rate in later stages.It has been gradually applied in clinical practice and has achieved certain results.This article discusses the application and development of arterial infusion chemotherapy in the neoadjuvant therapy for gastric cancer.

Objective:To investigate the efficacy of arthroscopic anatomical reconstruction of the ligament with autologous semitendinosus tendon in the treatment of chronic lateral ankle instability (CLAI) complicated with multiple ligament laxity.Methods:A retrospective study was conducted to analyze the 34 patients with CLAI plus multiple ligament laxity who had been treated at Foot and Ankle Surgery Center, The Fourth Hospital of Wuhan from March 2014 to December 2021. They were 8 males and 26 females with an age of (32.2±5.6) years. The patients were divided into 2 groups based on their treatment methods. A reconstruction group of 20 cases were treated by arthroscopic reconstruction of the ligament with autologous semitendinosus tendon while a repair group of 14 cases treated by arthroscopic repair of the ligament with the modified Brostr?m procedure. The 2 groups were compared in terms of surgical time, and the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, visual analog scale (VAS) pain score, talar tilt (TT), anterior translation of the talus (ATT), and complications at the last follow-up.Results:The 2 groups were comparable because there were no statistically significant differences in the general data, AOFAS ankle-hindfoot score, VAS pain score, TT, or ATT before surgery between the 2 groups ( P > 0.05). The surgical time for the reconstruction group [(97.5±11.4) min] was significantly longer than that for the repair group [(53.6±10.7) min] ( P < 0.05). All the 34 patients were followed up for (35.4±3.5) months. The TT, ATT, AOFAS ankle-hindfoot score, and VAS pain score at the last follow-up were all significantly improved compared with the preoperative values in both groups ( P < 0.05). The AOFAS ankle-hindfoot score [(90.6±3.6) points], TT (6.0°±1.5°), and ATT [(3.6±1.4) mm] at the last follow-up in the reconstruction group were all significantly better than those in the repair group [(84.1±11.0) points, 8.6°±4.3°, and (6.6±4.1) mm] ( P < 0.05). There was no statistically significant difference in the VAS pain score between the 2 groups at the last follow-up ( P > 0.05). All incisions healed at one stage without such complications as nerve or vascular injury. CLAI recurrence occurred in 5 cases in the repair group, significant worse than that in the reconstruction group (no recurrence) ( P=0.015). Conclusion:In the treatment of CLAI complicated with multiple ligament laxity, arthroscopic anatomical reconstruction of the ligament with autologous semitendinosus tendon can effectively improve ankle function, enhance ankle stability, and reduce recurrence of the condition.