BACKGROUND:Cervical disc herniation can cause pain in the neck and shoulder area,as well as radiating pain in the upper limbs.The incidence rate is increasing year by year and tends to affect younger individuals.Fully understanding the biomechanical characteristics of the cervical spine in adolescents is of great significance for preventing and delaying the onset of cervical disc herniation in this age group. OBJECTIVE:To reconstruct cervical spine models for both healthy adolescents and adolescent patients with cervical disc herniation utilizing finite element analysis techniques,to analyze the motion range of the C1-T1 cervical vertebrae as well as the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and the cartilage of the small joints. METHODS:A normal adolescent's cervical spine and an adolescent patient with cervical disc herniation were selected in this study.The continuous scan cervical spine CT raw image data were imported into Mimics 21.0 in DICOM format.The C1-T1 vertebrae were reconstructed separately.Subsequently,the established models were imported into the 3-Matic software for disc reconstruction.The perfected models were then imported into Hypermesh software for meshing of the vertebrae,nucleus pulposus,annulus fibrosus,and ligaments,creating valid geometric models.After assigning material properties,the final models were imported into ABAQUS software to observe the joint motion range of the C1-C7 cervical vertebrae segments under different conditions,and to analyze the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and small joint cartilage of each cervical spine segment. RESULTS AND CONCLUSION:(1)In six different conditions,the joint motion range of the C1 vertebra in the cervical spine models of both normal adolescent and adolescent patient with cervical disc herniation was higher than that of the other vertebrae.Additionally,the joint motion range of each cervical spine segment in normal adolescent was greater than that in adolescent patient with cervical disc herniation.(2)In the cervical spine model of normal adolescent,the maximum stress values in the annulus fibrosus and nucleus pulposus were found on the left side during C2-3 flexion conditions(0.43 MPa and 0.17 MPa,respectively).In the cervical spine model of adolescent patient with cervical disc herniation,the maximum stress values were found on the left side during C7-T1 flexion conditions(0.54 MPa and 0.18 MPa,respectively).(3)In the cervical spine model of normal adolescent,the maximum stress value on the endplate was found on the left side of the upper endplate of C3 during flexion conditions(1.46 MPa).In the model of adolescent patient with cervical disc herniation,the maximum stress value on the endplate was found on the left side of the lower endplate of C7 during flexion conditions(1.32 MPa).(4)In the cervical spine model of normal adolescent,the maximum stress value in the small joint cartilage was found in the C2-3 left rotation conditions(0.98 MPa).In adolescent patient with cervical disc herniation,the stress in the small joint cartilage significantly increased under different conditions,especially in C1-2,with the maximum stress found during left flexion(3.50 MPa).(5)It is concluded that compared to normal adolescent,adolescent patient with cervical disc herniation exhibits altered cervical curvature and a decrease in overall joint motion range in the cervical spine.In adolescent with cervical disc herniation,there is a significant increase in stress on the annulus fibrosus,nucleus pulposus,and endplates in the C7-T1 segment.The stress on the left articular cartilage of the C1-2 is notable.Abnormal cervical curvature may be the primary factor causing these stress changes.

Skin wounds are global public problems,especially in terms of the difficult healing of chronic wounds,which may seriously affect patients'lives.Most skin-wound animal models are currently established by physical method,and different animal models have different biological characteristics.This review therefore classifies mouse,rat,and other animal models of skin wounds according to the literature,summarizes and analyzes the construction of skin-wound animal models based on physical method and evaluation indicators,and considers the advantages and disadvantages of different animal models,to provide a basis for the rational construction of skin-wound animal models and drug research and development.

Objective To establish a rapid detection method for invasive candidiasis based on droplet digital polymerase chain reaction(ddPCR).Methods We developed an assay system using a microtitre-based digital PCR platform and designed primer probes specific for four Candida species,namely Candida albicans,Candida smoothii,Candida near-smoothii,and Candida tropicalis.(1)The Limit of Blank(LOB)range and positive judg-ment value were determined by analyzing No Template Control(NTC)samples.(2)The Limit of Detection(LOD)range was determined by diluting positive samples with 10 replicate extractions at each concentration gradient.(3)The Linear Limit of Quantitation(LOQ)range was determined by repetitive testing of diluted samples.(4)The linear range limit was determined through gradient dilution of the positive samples.(5)The coefficient of variation(CV),calculated from the logarithmic values of the resultant concentrations,was assessed by extracting and test-ing positive samples in 12 repetitions at both high and low concentrations.(6)Method reliability was evaluated by calculating the CV from the logarithmic values of the resultant concentrations obtained from clinical samples with fungal culture results.Results The ddPCR assay detected Candida LOB at a range of 0～81 copies/mL,with a positive threshold set at≥3 positive microdroplets.The LOD and LOQ were determined to be 3×102 copies/mL.The linear range for detecting different concentration gradients was found to be between 3×102 and 3×107 copies/mL,with high correlation coefficients observed for Candida albicans(R2=0.999 5),Candida smoothii(R2=0.998 9),Candida near-smoothii(R2=0.999 4),and Candida tropicalis(R2=0.999).Additionally,the coefficient of variation for the resultant concentration logarithmic values was less than 5%,meeting precision requirements.Furthermore,preliminary validation using clinical specimens demonstrated consistent results compared to clinical culture findings.Conclusion ddPCR exhibits rapidity,high sensitivity,good repeatability,and high specificity in detecting inva-sive candidiasis in critically ill patients.This study highlights the potential value of droplet digital PCR as a diag-nostic tool for invasive candidiasis.

In the context of the digital economy， the operational relationship between traditional Chinese medicine （TCM） and Internet healthcare organizations as well as related governance institutions has attracted much attention. As the market scale of the Internet healthcare has continued to grow in recent years， the quality of Internet TCM healthcare has also been improved. By analyzing the development status of Internet TCM healthcare， it is proposed that Internet TCM health service should seize the opportunities and challenges in future， promote the growth of market scale from varied aspects， enhance patient-centered care awareness， and strengthen the promotion and popularization of digital services， thereby promoting the high-quality development of Internet TCM health service in the context of the digital economy.

Objective:To examine the effects of apelin-13 on ferroptosis of the C2C12 skeletal muscle cell line induced by a high-iron environment and explore potential underlying mechanisms.Methods:C2C12 cells were cultured in Dulbecco's Modified Eagle Medium(DMEM)and divided into a control group, a ferric citrate(FAC)group, an apelin-13 group, an FAC+ apelin-13 group, a ferroptosis inducer RSL3 group and an FAC+ apelin-13+ RSL3 group.Cell viability was detected by the 3-(4, 5-dimethyl thiazole-2)-2, 5-diphenyl thiazolyl blue(MTT)assay.The intracellular concentrations of total iron and divalent iron were measured by colorimetry; the levels of glutathione(GSH), malondialdehyde(MDA)and intracellular reactive oxygen species(ROS)in cells were detected by an enzyme-linked immunosorbent assay, visible spectrophotometry and a chemifluorescence method, respectively.The ultrastructure of C2C12 cells was examined by transmission electron microscopy.The protein expression of glutathione peroxidase 4(GPX-4), ferritin heavy chain 1(FTH-1), heme oxygenase 1(HO-1)and nuclear factor E2-related factor 2(Nrf-2), were detected by Western blotting.Results:Compared with the FAC group, the FAC+ Apelin-13 group had significantly elevated cell viability(optical density: 0.52±0.06 vs.0.28±0.04, t=7.837, P=0.007)and higher concentrations of GSH(2.41±0.35 vs.0.91±0.12 μmol/g Pro, t=9.778, P=0.003), but significantly decreased levels of ROS(22.06±5.79 vs.52.71±7.28 a. u./mg Pro, t=8.064, P=0.006), MDA(4.63±0.51 vs.9.11±0.84 mmol/mg Pro, t=8.642, P=0.006), total iron(1.53±0.24 vs.3.17±0.55 μmol/g Pro, t=6.135, P=0.013)and divalent iron(0.75±0.08 vs.1.94±0.36 μmol/g Pro, t=5.068, P=0.027), as well as reduced intracellular iron deposition.In the control group and the apelin-13 group, the morphology of the mitochondria was clear and normal.In contrast, the mitochondria in the FAC group had increased membrane density, membrane shrinkage and rupture, vacuolar degeneration, and obvious mitochondrial damage, which were consistent with the morphological characteristics of ferroptosis.Compared with the FAC group, the FAC+ apelin-13 group showed significant improvement in mitochondrial damage.Moreover, compared with the FAC+ apelin-13 group, the cell viability of the FAC+ apelin-13+ RSL3 group was significantly decreased(optical density: 0.23±0.04 vs.0.48±0.06, t=7.642, P=0.007). Compared with the FAC group, the FAC+ apelin-13 group had significantly up-regulated cellular expression of GPX-4(relative expression: 0.96±0.14 vs.0.31±0.07, t=7.712, P=0.008), FTH-1(0.57±0.08 vs.0.27±0.05, t=6.944, P=0.011), and HO-1(0.49±0.07 vs.0.28±0.05, t=6.472, P=0.012), as well as increased nuclear expression of Nrf-2(relative expression: 0.42±0.04 vs.0.19±0.05, t=7.114, P=0.008)with a higher ratio of nuclear expression over total cellular expression[(58.36±5.24)% vs.(36.58±5.32)%, t=5.858, P=0.015]and a higher level of HO-1 protein expression(relative expression: 0.49±0.07 vs.0.28±0.05, t=6.472, P=0.012). Conclusions:Apelin-13 inhibits ferroptosis induced by a high iron environment in C2C12 cells, and the underlying molecular mechanisms may be related to the Nrf-2/HO-1 signaling pathway.

Objective:To explore the safety of inactivating coronavirus disease 2019(covid-19)vaccine in liver transplantation(LT)recipients.Methods:Retrospective analysis was performed for clinical data of 151 LT recipients from March 2003 to October 2019.They had stable conditions and completed the course of covid-19 vaccine.Frequencies of pain at injection site, fatigue, headache and pruritus after vaccination were recorded.The safety profiles were compared between recipients with and without local and general adverse reactions after vaccination.At the same time, recipients completing two doses of covid-19 vaccines were grouped.According to vaccine companies, they were classified into Sinovac Biotech Ltd and Beijing Biological.Based upon more than or less than 60 years, they were grouped into <60 years and ≥60 years.The safety profiles of inactivating COVID-19 vaccine were compared in subgroups.Results:Among 151 eligible LT recipients, 98 of them were in group of age <60 years and 53 in group of age >60 years.The median period between vaccination and LT was 8.44(4.37, 12.39)years and the median concentration of tacrolimus 2.5(1.8, 3.9)ng/L.Eighty-three cases completed two doses of Sinovac Biotech Ltd(Sinovac Biotech Ltd group)and 40 cases Beijing Biological(Beijing Biological group); 14 cases had combined course of Sinovac Biotech Ltd and Beijing Biological, four recipients were vaccinated with inactivated vaccine from other companies and ten recipients did not know their inactivated vaccine' companies.After immunization, 24/151(15.9%)recipients had a local and general adverse reaction.The prevalence of pain at injection site, fatigue, headache and pruritus was 9.9%( n=15), 5.2%( n=8), 1.3%( n=2)and 0.7%( n=1)respectively.No significant differences existed in age( P=0.602), gender( P=0.752), period after LT( P=0.890), trough concentration of tacrolimus( P=0.377)or versions of covid-19 vaccine( P=0.582)between 24 cases with general adverse reaction and 127 without.Local and general reactions occurred in 16/83(19.3%)in Sinovac group and 5/40(12.5%)in Beijing Biological.There was no significant inter-group difference( P=0.769). There were 98 cases(64.9%)in <60 years group, 17 cases(17.3%)had local and general reaction, 53 cases(35.1%)in ≥60 years group and 7 cases(13.2%)had a local and systemic reaction.There was no significant inter-group difference( P=0.507). Conclusions:Covid-19 vaccine is safe for long-term survival LT recipients with normal liver function.Few participants present with mild fatigue and pain at injection site.

ObjectiveTo compare the functional connectivity of brain networks in stroke patients with upper limb motor dysfunction during unilateral or bilateral upper limb movement using functional near-infrared spectroscopy (fNIRS). MethodsFrom April to June, 2021, 40 stroke patients with upper limb motor dysfunction in Department of Rehabilitation Medicine, Huashan Hospital, finished unilateral (affected) and bilateral upper limb movement. Eight-minute fNIRS data were collected before and after movement, and the functional activities and connectivity of prefrontal cortex (PFC), upper limb and hand functional area (H), primary sensory cortex (S1) were analyzed based on oxygenated hemoglobin. ResultsFunctional activities increased in affected H after unilateral task (t = -3.135, P < 0.05), while the functional connectivity increased between affected H and affected S1, affected H and unaffected S1, and affected S1 and unaffected S1 (|t| > 3.218, P < 0.05). There was no significant difference in the functional activities and connectivity of all the areas after bilateral upper limb task (|t| < 2.385, P > 0.05). The improvement of affected H was more after unilateral task than after bilateral upper limb task (t = 2.026, P < 0.05). ConclusionUnilateral affected upper limb training is more effective on functional activities and connectivity for corresponding brain regions than bilateral task.

Objective:To observe the effect of Apelin-13 on diabetes-related sarcopenia in rats model and explore the underlying mechanism.Methods:This experiments were divided into 3 groups.In the normal control group, Wistar rats were fed by ordinary feed, intraperitoneally injected daily with the equal amount of normal saline.In the model+ control group, diabetic-related sarcopenia model was established in rats with fat-fed Goto-Kakizaki rats for 12 weeks and intraperitoneally injected daily with the equal amount of normal saline.In the model+ apelin-13 group, apelin-13(0.1 mol/kg)was intraperitoneally injected into diabetic-related sarcopenia model daily for 12 weeks.The water intake, food intake, and body weight were measured.The fasting blood glucose, fasting insulin and blood lipid levels of rats were measured, and the insulin resistance index was calculated.The wet weight of the rats' gastrocnemius muscle was weighed, and the morphological changes of the gastrocnemius muscle were observed.Western blot was used to detect the protein expressions of phosphatidylinositol-3 kinase(PI3K)and phosphorylated Akt(p-Akt)in the gastrocnemius muscle of rats.Results:Compared with the model+ normal saline group, the model+ apelin-13 group showed that the following parameters were significantly improved.(1)The water intake of rats was significantly decreased at 8, and 12 weeks( F=7.17 and 7.91), and food intake was significantly decreased( F=5.84 and 6.12)and body weight were significantly increased at 8 and 12 weeks( F=5.76 and 6.07)(all P<0.05). (2)The levels of fasting blood glucose were significantly decreased at 8 and 12 weeks( F=8.07 and 8.24, all P<0.05). (3)Serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, the levels fasting insulin and the insulin resistance index were significantly decreased at week 12( F=5.17, 7.94, 10.27, 8.32, 6.94 and 11.31, all P<0.05); (4)The wet weight of gastrocnemius muscle was significantly increased(0.63±0.04 g and 1.02±0.05 g, t=4.32, P<0.05). (5)Compared with the model+ normal saline group, the model+ apelin-13 group showed the protein expressions of PI3K and p-Akt in the gastrocnemius muscle of rats were significantly up-regulated( t=7.32, 8.07, both P<0.05). Conclusions:Apelin-13 has an inhibitory effect on diabetes-related sarcopenia, and its mechanism may be related to the up-regulation of PI3K and p-Akt expression in skeletal muscle.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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