Transmembrane protein 33(TMEM33)is up-regulated in the majority of cancers.To change the expression of TMEM33 can significantly affect the proliferation,migration,and invasion of renal and cervical cancer cells.Its mechanisms of action may involve four aspects:1)participation in lipid metabolism;2)regu-lation of endoplasmic reticulum;3)regulation of intracellular calcium homeostasis;4)participation in angio-genesis.

Objective This study aimed to explore the expression pattern of transmembrane protein 33(TMEM33)in lung adenocarcinoma and its correlation with clinical pathological features.Methods Bioinformatics tools and public databases(e.g.,TCGA and GEO)were used to analyze TMEM33 expression data in lung cancer.Then,immunoblotting and real-time quantitative PCR were performed to detect TMEM33 protein and mRNA levels in four cell lines.Immunofluorescence and immunohistochemistry were also used to assess TMEM33 expression and localization in lung adenocarcinoma and normal lung tissue samples.Results Bioinformatics analysis revealed higher TMEM33 expression in lung adenocarcinoma than in normal lung tissue(P＜0.05)and a significant correlation between TMEM33 and SLC30A9 expression(P＜0.0001).Logistic regression analysis indicated an association between TMEM33 expression and tumor T stage(OR=0.48,P=0.044).Experimental results showed higher TMEM33 protein(P＜0.01)and mRNA(P＜0.001)levels in lung adenocarcinoma cell lines than in normal lung epithelial cells.Similarly,TMEM33 protein(P＜0.05)and mRNA(P＜0.01)levels were higher in lung adenocarcinoma tissues than in adjacent tissues.Immunohistochemistry confirmed high TMEM33 expression in lung adenocarcinoma tissues.Conclusion TMEM33 is highly expressed in lung adenocarcinoma,associated with malignancy and T stage,and may be a potential prognostic and therapeutic target.

Objective To investigate the impact of DNA damage-regulated autophagy factor 2(DRAM2)on the proliferation and migration of non-small cell lung cancer(NSCLC)cells through tumor protein p53(p53)and autophagy.Methods DRAM2 gene was knocked down using lentiviral technology to establish NSCLC cell lines,and autophagy markers were detected by immunofluorescence and Western blot.CCK8 and Transwell assays were used to detect cell proliferation and migration.The effects of autophagy activation and p53 knockdown on autoph-agy and functions of DRAM2?knockdown cells were examined.Results Knockdown of DRAM2 inhibited NSCLC cells,with upregulation of p62 expression(P<0.05)and decreased level of LC3?Ⅱ(P<0.05).Knockdown of DRAM2 suppressed the proliferation(P<0.001)and migration(P<0.001)of NSCLC cells.Activation of auto?phagy partially reversed the inhibitory effects of DRAM2 knockdown on cell proliferation(P<0.01)and migration(P<0.01).When DRAM2 and p53 were knocked down simultaneously,autophagy,cell proliferation(P<0.05)and migration abilities(P<0.001)were restored.Conclusions Knockdown of DRAM2 inhibits the proliferation and migration of lung cancer cell line A549,providing a potential intervention direction for the devel?opment of therapeutic strategies.

Objective To explore the clinical efficacy of applying exoskeleton robots in lower limb functional rehabilitation for patients after minimally invasive surgery for cervical spondylotic myelopathy(CSM).Methods A retrospective analysis was conducted on the clinical data of 56 patients who underwent spinal endoscopic minimally invasive surgery between April 2021 and October 2022.Based on the rehabilitation methods,patients were divided into the observation group(robot-assisted rehabilitation group)and the control group(conventional rehabilitation group).The Japanese Orthopaedic Association(JOA)scores for cervical spinal cord function,lower limb somatosensory evoked potential amplitudes,and gait analysis indicators(step frequency,walking speed,and stance phase ratio)were assessed preoperatively,4 weeks postoperatively,and 8 weeks postoperatively.Results In 4 and 8 weeks after surgery,both groups showed significant improvements in JOA scores,lower-limb somatosensory evoked potential amplitudes,and gait parameters(step frequency,walking speed,and stance phase ratio)com-pared with preoperative data(P<0.05).Furthermore,the improvements in JOA scores,somatosensory evoked potential amplitudes,and gait parameters in the observation group were significantly greater than those in the control group at both 4 and 8 weeks postoperatively(P<0.05).However,at the 2-year follow-up,there were no statistically significant differences(P>0.05)between the two groups in any of these measures.Conclusions Rehabilitation using lower limb exoskeleton robots can accelerate spinal cord function recovery and improve lower limb walking ability in patients after minimally invasive surgery for CSM,demonstrating superior short-term clinical efficacy com-pared to conventional rehabilitation.However,no significant differences were observed between the two methods during long-term follow-up.

Objective To explore the clinical efficacy of applying exoskeleton robots in lower limb functional rehabilitation for patients after minimally invasive surgery for cervical spondylotic myelopathy(CSM).Methods A retrospective analysis was conducted on the clinical data of 56 patients who underwent spinal endoscopic minimally invasive surgery between April 2021 and October 2022.Based on the rehabilitation methods,patients were divided into the observation group(robot-assisted rehabilitation group)and the control group(conventional rehabilitation group).The Japanese Orthopaedic Association(JOA)scores for cervical spinal cord function,lower limb somatosensory evoked potential amplitudes,and gait analysis indicators(step frequency,walking speed,and stance phase ratio)were assessed preoperatively,4 weeks postoperatively,and 8 weeks postoperatively.Results In 4 and 8 weeks after surgery,both groups showed significant improvements in JOA scores,lower-limb somatosensory evoked potential amplitudes,and gait parameters(step frequency,walking speed,and stance phase ratio)com-pared with preoperative data(P<0.05).Furthermore,the improvements in JOA scores,somatosensory evoked potential amplitudes,and gait parameters in the observation group were significantly greater than those in the control group at both 4 and 8 weeks postoperatively(P<0.05).However,at the 2-year follow-up,there were no statistically significant differences(P>0.05)between the two groups in any of these measures.Conclusions Rehabilitation using lower limb exoskeleton robots can accelerate spinal cord function recovery and improve lower limb walking ability in patients after minimally invasive surgery for CSM,demonstrating superior short-term clinical efficacy com-pared to conventional rehabilitation.However,no significant differences were observed between the two methods during long-term follow-up.

Objective To investigate the impact of DNA damage-regulated autophagy factor 2(DRAM2)on the proliferation and migration of non-small cell lung cancer(NSCLC)cells through tumor protein p53(p53)and autophagy.Methods DRAM2 gene was knocked down using lentiviral technology to establish NSCLC cell lines,and autophagy markers were detected by immunofluorescence and Western blot.CCK8 and Transwell assays were used to detect cell proliferation and migration.The effects of autophagy activation and p53 knockdown on autoph-agy and functions of DRAM2?knockdown cells were examined.Results Knockdown of DRAM2 inhibited NSCLC cells,with upregulation of p62 expression(P<0.05)and decreased level of LC3?Ⅱ(P<0.05).Knockdown of DRAM2 suppressed the proliferation(P<0.001)and migration(P<0.001)of NSCLC cells.Activation of auto?phagy partially reversed the inhibitory effects of DRAM2 knockdown on cell proliferation(P<0.01)and migration(P<0.01).When DRAM2 and p53 were knocked down simultaneously,autophagy,cell proliferation(P<0.05)and migration abilities(P<0.001)were restored.Conclusions Knockdown of DRAM2 inhibits the proliferation and migration of lung cancer cell line A549,providing a potential intervention direction for the devel?opment of therapeutic strategies.

OBJECTIVE: To explore the pathogenesis of two siblings (including a fetus) from a pedigree affected with Joubert syndrome. METHODS: Peripheral blood samples of the proband and his parents as well as amniotic fluid and abortion tissues of the fetus were collected. Part of the samples were used for the extraction of DNA, and whole exome sequencing (WES) was carried out to screen potential variants in the proband and his parents. Suspected variants were subjected to bioinformatics analysis with consideration of the clinical phenotype, and were verified by Sanger sequencing of the proband, fetus and their parents.The remainders were used for the extraction of RNA, and the mechanism of splicing variant was validated by reverse transcription-PCR (RT-PCR). RESULTS: WES showed that both patients have carried c.175C>T (p.R59X) and c.553+1G>A compound heterozygous variants of the TMEM237 gene. Among these, c.175C>T was a nonsense mutation inherited from the asymptomatic mother, while c.553+1G>A was an alternative splicing mutation inherited from the asymptomatic father. RT-PCR showed that this variant has resulted in aberrant splicing by exon skipping. CONCLUSION The compound heterozygous variants of the TMEM237 gene probably underlay the etiology of Joubert syndrome in this pedigree. Above finding has enriched the phenotype and variant spectrum of the TMEM237 gene, and facilitated genetic counseling and prenatal diagnosis for the family.
Abnormalities, Multiple/genetics* ; Cerebellum/abnormalities* ; Eye Abnormalities ; Female ; Genotype ; Humans ; Kidney Diseases, Cystic ; Mutation ; Pedigree ; Phenotype ; Pregnancy ; Retina/abnormalities*

BACKGROUND:Transplanted neural stem cel s can survive, proliferate and differentiate into neurons and/or glial cel s in the host, thereby promoting partial function recovery in the host.
OBJECTIVE:To study the therapeutic effects of neural stem cel transplantation on cerebral palsy rats. METHODS:Twenty-four rats were randomly divided into three groups:control group, model group and transplantation group. Animal models of cerebral palsy were made in the latter two groups. One week after modeling, rats in the transplantation group were injected 1 mL stem cel suspension (1×105) via the jugular vein, and rats in the control and model group were given the same volume of normal saline. Toe distance, step length and elevated body swing test in rats were detected, and histopathological changes in the rat brain were observed 3 weeks after transplantation.
RESULTS AND CONCLUSION:In the model group, the toe distance and step length of the front left palm were significantly lower than those of the front right palm (P<0.05). Compared with the model group, the toe distance and step length in the transplantation and control groups were significantly increased (P<0.05). In the elevated body swing test, rats in the model group presented with asymmetric swing of the
body, but rats in the other two groups exhibited symmetric swing of the body (P<0.05). Additional y, the ratio of right to left hemispheric areas was significantly higher in the transplantation and control groups compared with the model group (P<0.05). In conclusion, neural stem cel transplantation via the jugular vein can improve brain function and restore motor function in rats with cerebral palsy.

OBJECTIVE:To observe clinical efficacy and safety of naloxone hydrochloride combined with Danshen injection in the treatment of neonatal hypoxic ischemic encephalopathy(HIE). METHODS:104 patients with HIE were randomly divided into observation group and control group with 52 cases in each group. The control group was treated with Naloxone hydrochloride injec-tion 0.02 mg/kg,ivgtt,qd and conventional symptomatic treatment;while observation group was additionally treated with Danshen injection 4-6 ml+10% Glucose injection 20 ml,ivgtt,qd,on the basis of the control group. Treatment course of 2 groups lasted for 7 d. Clinical efficacy,symptom and sign recovery of 2 groups were compared,as well as levels of serum MMP-9,IL-6 and TNF-α,cerebral hemodynamic parameters and ADR. RESULTS:There was no statistical significance in MMP-9,IL-6,TNF-α and cerebral hemodynamic parameters before treatment(P>0.05). The total effective rate of observation group(92.31%)was signifi-cantly higher than that of control group (75.00%);after treatment,the recovery time of consciousness disturbance,primitive re-flex and muscle tension in the observation group were shorter than those in the control group;the levels of serum MMP-9,IL-6 and TNF-α in observation group were significantly lower than those in control group;peak systolic flow velocity(PSFV),end-dia-stolic flow velocity (EDTV) were higher in the observation group than in the control group,with statistical significance (P<0.05);resistance index (RI) was lower than in control group,but without statistical significance (P>0.05). No ADR was ob-served in 2 groups. CONCLUSIONS:Naloxone hydrochloride combined with Danshen injection can significantly promote HIE and signs recovery,reduce the levels of serum MMP-9,IL-6 and TNF-α,and improve hemodynamic parameters with good safety.

Objective To investigate the effect of sulforaphane synergistic with lithium chloride on neuroprotective of rats with traumatic brain injury. Methods According to feeney method free fall production models of traumatic brain injury induced injury models, and rats were divided into control group, model group, SFN group and collaborative group, each group 15 rats, control group without impact experiment, after operation the SFN group received daily intraperitoneal injection of sulforaphane, collaborative group were given sulforaphane and chloride lithium intraperitoneal injection, the model group received daily intraperitoneal injection of saline, the degree of nerve function impairment score (mNSS) in rats of each group postoperative 1 d, 3 d, 5 d and 7 d, and brain tissue of rats, the water content of brain tissue, HE staining of brain tissue and activity of SOD, IL-6, TNF-alpha, the level of MDA in each group postoperative 7 d were compared. Results Compared with the control group, mNSS scores in the model group, SFN group, collaborative group at each time point were significantly increased (P<0.05); After 5 d, 7 d of operation, synergy scores in SFN group and mNSS group rats were significantly lower than those in the model group (P<0.05), and mNSS score in collaborative group was significantly lower than that of SFN group(P<0.05); After 7 d of operation, the brain tissue water content in control group of rats was (69.29±2.06)%, the model group was(75.40±1.73)%, SFN group was (73.08±1.06)%, collaborative group was (71.27±1.52)%; Brain tissue HE staining results showed that the nerve cell injury of rats in SFN group and cooperative group was obviously alleviated than those in the model group, necrotic cells decreased, and the collaborative group relieve neuronal injury was the most remarkable; The SOD in model group, SFN group, collaborative group decreased significantly compared with the control group (P<0.05), IL-6, TNF-alpha, MDA levels increased significantly(P<0.05);The activity of SOD in SFN group and collaborative group increased significantly compared with the model group(P<0.05), IL-6, TNF-alpha, MDA levels decreased significantly (P<0.05), and collaborative TNF-alpha and IL-6 levels were significantly lower than that of SFN group (P<0.05). Conclusion Sulforaphane in combination with lithium chloride have remarkable neuroprotection on traumatic brain injury in rats, its mechanism may be related with the reduction of brain edema in rats, nerve cell damage, inhibition of oxidative stress and related to the release of inflammatory factors.