BACKGROUND:Previous studies have found that neuronal damage caused by continuous excessive fluoride exposure is related to Ca2+overload,but the mechanism of Ca2+flow conversion between intracellular calcium stores and cell apoptosis damage is still unclear.OBJECTIVE:To investigate the effect of fluoride exposure on Ca2+transport channel proteins and apoptosis levels in the mitochondria-associated endoplasmic reticulum membrane of primary cultured neural cells.METHODS:Primary nerve cells of neonatal SD rats were cultured in vitro and identified by immunofluorescence staining with neuronal nucleus-specific antibody up to day 7.The nerve cells were divided into control group(containing 0 mmol/L sodium fluoride),low fluoride group(containing 0.5 mmol/L sodium fluoride),and high fluoride group(containing 1 mmol/L sodium fluoride).The cell morphological changes were observed by light microscope 24 hours after fluorine exposure.The expression levels of apoptosis-related protein BAX/BCL-2 and calcium transfer-related pathways VDAC1,GRP 75,and IP3R were detected using western blot assay.The expression levels of VDAC1,GRP 75,and IP3R mRNA were detected by RT-PCR.Ca2+levels were detected by Rhood-2AM Ca2+probe.Mitochondrial membrane potential detection kit was used to detect the change in mitochondrial membrane potential.The level of apoptosis was determined by flow cytometry and TUNEL staining.RESULTS AND CONCLUSION:(1)The purity of neurons cultured on day 7 had been determined to be over 90％,with few impurities,good growth status,and tight cell network connections,meeting the requirements of subsequent experiments.(2)Compared with the control group,growth of neural cell clusters in the low-fluoride group and the high-fluoride group increased;the processes were broken;the cell body was rounded,and the connection network between cells was destroyed.Compared with the low-fluoride group,the cell damage changes in the high-fluoride group were more obvious.(3)Compared with the control group,the protein expressions of VDAC1,GRP75,and IP3R were increased in the low-fluoride group and the high-fluoride group(P＜0.05),and the ratio of apoptosis-related protein BAX/BCL-2 was increased(P＜0.05).Compared with the control group,the expression of VDAC1 and GRP75 mRNA in the low-fluoride group was significantly increased(P＜0.05);the expression levels of VDAC1,GRP75,and IP3R mRNA in the high-fluoride group were significantly increased(P＜0.01).(4)The level of cell apoptosis increased significantly after fluoride exposure,and the high-fluoride group was significantly higher than the control and low-fluoride groups(P＜0.01).(5)After fluoride exposure,the concentration of mitochondrial Ca2+in nerve cells increased significantly(P＜0.05),the mitochondrial membrane potential decreased(P＜0.01),and the degree of damage in the high-fluoride group was more obvious(P＜0.05).The results show that fluoride exposure impairs the morphological structure of primary neural cells,resulting in upregulation of Ca2+transfer pathway protein expression between the endoplasmic reticulum and mitochondria,mitochondrial Ca2+overload,mitochondrial damage,and increased levels of apoptosis.

BACKGROUND:Previous studies have found that neuronal damage caused by continuous excessive fluoride exposure is related to Ca2+overload,but the mechanism of Ca2+flow conversion between intracellular calcium stores and cell apoptosis damage is still unclear.OBJECTIVE:To investigate the effect of fluoride exposure on Ca2+transport channel proteins and apoptosis levels in the mitochondria-associated endoplasmic reticulum membrane of primary cultured neural cells.METHODS:Primary nerve cells of neonatal SD rats were cultured in vitro and identified by immunofluorescence staining with neuronal nucleus-specific antibody up to day 7.The nerve cells were divided into control group(containing 0 mmol/L sodium fluoride),low fluoride group(containing 0.5 mmol/L sodium fluoride),and high fluoride group(containing 1 mmol/L sodium fluoride).The cell morphological changes were observed by light microscope 24 hours after fluorine exposure.The expression levels of apoptosis-related protein BAX/BCL-2 and calcium transfer-related pathways VDAC1,GRP 75,and IP3R were detected using western blot assay.The expression levels of VDAC1,GRP 75,and IP3R mRNA were detected by RT-PCR.Ca2+levels were detected by Rhood-2AM Ca2+probe.Mitochondrial membrane potential detection kit was used to detect the change in mitochondrial membrane potential.The level of apoptosis was determined by flow cytometry and TUNEL staining.RESULTS AND CONCLUSION:(1)The purity of neurons cultured on day 7 had been determined to be over 90％,with few impurities,good growth status,and tight cell network connections,meeting the requirements of subsequent experiments.(2)Compared with the control group,growth of neural cell clusters in the low-fluoride group and the high-fluoride group increased;the processes were broken;the cell body was rounded,and the connection network between cells was destroyed.Compared with the low-fluoride group,the cell damage changes in the high-fluoride group were more obvious.(3)Compared with the control group,the protein expressions of VDAC1,GRP75,and IP3R were increased in the low-fluoride group and the high-fluoride group(P＜0.05),and the ratio of apoptosis-related protein BAX/BCL-2 was increased(P＜0.05).Compared with the control group,the expression of VDAC1 and GRP75 mRNA in the low-fluoride group was significantly increased(P＜0.05);the expression levels of VDAC1,GRP75,and IP3R mRNA in the high-fluoride group were significantly increased(P＜0.01).(4)The level of cell apoptosis increased significantly after fluoride exposure,and the high-fluoride group was significantly higher than the control and low-fluoride groups(P＜0.01).(5)After fluoride exposure,the concentration of mitochondrial Ca2+in nerve cells increased significantly(P＜0.05),the mitochondrial membrane potential decreased(P＜0.01),and the degree of damage in the high-fluoride group was more obvious(P＜0.05).The results show that fluoride exposure impairs the morphological structure of primary neural cells,resulting in upregulation of Ca2+transfer pathway protein expression between the endoplasmic reticulum and mitochondria,mitochondrial Ca2+overload,mitochondrial damage,and increased levels of apoptosis.

Objective:To observe the effect of ankle joint proprioception training on ankle joint proprioception, balance and gait in patients with thalamic infarction.Methods:Fifty-six patients with thalamic infarction were divided into a control group and a treatment group, each of 28, using a random number table. Both groups were given conventional lower limb rehabilitation training, but the treatment group was additionally provided with ankle joint proprioception training. Before and after 4 weeks of the treatment, the Tecnobody proprioception testing system was used to determine the average trajectory error rate (ATE) and the time taken in the test. The Berg Balance Scale (BBS) and a balance tester were used to assess balance. A gait analyzer was used to collect spatial-temporal measures of the patients′ walking, including the stride amplitude, stride rate, the proportion of the time spent in the swing phase, and foot dorsiflexion and plantarflexion angles.Results:After the treatment, the time used, ATE, ankle proprioception, BBS scores, static balance test scores, stability limits, stride length, stride rate, swing phase time percentage, and foot dorsiflexion and plantarflexion angles had improved in both groups compared with before the treatment ( P≤0.05). Compared with the control group, the treatment group had a smaller average ATE, spent less time on the ankle proprioception test, had higher BBS scores, had lower scores on the static balance test, had larger limits of stability, took longer strides at a faster rate, and spent a greater percentage of time in the swing phase. That group also showed greater ankle dorsiflexion and plantarflexion on average ( P≤0.05). ATE difference of the affected lower limb and the time to complete the ankle proprioception test were positively correlated with the gap in the static balance ability test, and negatively correlated with the gaps in the BBS score, the limits of stability, stride length, stride rate, and the time share of the swing phase, as well as the dorsiflexion and plantarflexion angles of the foot. Conclusions:Ankle proprioception training, in addition to effectively improving ankle proprioception, can improve the balance and gait of persons with thalamic infarction. It is worthy of clinical application and promotion.

Objective:To observe the effect of ankle joint proprioception training on ankle joint proprioception, balance and gait in patients with thalamic infarction.Methods:Fifty-six patients with thalamic infarction were divided into a control group and a treatment group, each of 28, using a random number table. Both groups were given conventional lower limb rehabilitation training, but the treatment group was additionally provided with ankle joint proprioception training. Before and after 4 weeks of the treatment, the Tecnobody proprioception testing system was used to determine the average trajectory error rate (ATE) and the time taken in the test. The Berg Balance Scale (BBS) and a balance tester were used to assess balance. A gait analyzer was used to collect spatial-temporal measures of the patients′ walking, including the stride amplitude, stride rate, the proportion of the time spent in the swing phase, and foot dorsiflexion and plantarflexion angles.Results:After the treatment, the time used, ATE, ankle proprioception, BBS scores, static balance test scores, stability limits, stride length, stride rate, swing phase time percentage, and foot dorsiflexion and plantarflexion angles had improved in both groups compared with before the treatment ( P≤0.05). Compared with the control group, the treatment group had a smaller average ATE, spent less time on the ankle proprioception test, had higher BBS scores, had lower scores on the static balance test, had larger limits of stability, took longer strides at a faster rate, and spent a greater percentage of time in the swing phase. That group also showed greater ankle dorsiflexion and plantarflexion on average ( P≤0.05). ATE difference of the affected lower limb and the time to complete the ankle proprioception test were positively correlated with the gap in the static balance ability test, and negatively correlated with the gaps in the BBS score, the limits of stability, stride length, stride rate, and the time share of the swing phase, as well as the dorsiflexion and plantarflexion angles of the foot. Conclusions:Ankle proprioception training, in addition to effectively improving ankle proprioception, can improve the balance and gait of persons with thalamic infarction. It is worthy of clinical application and promotion.

Objective To evaluate the application value of the second generation snap shot freeze(SSF2)combined with artificial intelligence reconstruction in free heart rate coronary computed tomography angiography(CCTA).Methods The examination data of 37 patients undergoing CCTA were divided into two groups for reconstruction.Group A,reconstruction by artificial intelligence after SSF2 algorithm correction;group B,original images automatically split and multi-phase reconstruction by artificial intelligence.Image quality were compared on volume rendering(VR),curve planar reformation(CPR),maximum intensity projection(MIP)image,subjective evaluation,objective scoring,and signal-to-noise ratio(SNR).Independent samples t-test and Chi-square test were used,and P<0.05 was considered statistically significant.Results There were statistically significant differences in the image quality score and SNR of the two reconstruction methods(P=0.009).Group A scored better,with higher signal intensity,lower noise intensity,and better SNR.The difference in the number of right coronary artery(RCA)analyzable segments between the two groups was statistically significant(P<0.05).The excellent and good rate of subjective evaluation of coronary artery segments in group A RCA(98.6%)was higher than that in group B(69.6%).Conclusion Using SSF2 combined with artificial intelligence reconstruction technology can significantly improve the image quality of CCTA,improve the success rate of CCTA examination,and improve the overall work efficiency.

Objective:To compare the characteristics of gait disorders between patients with idiopathic normal pressure hydrocephalus(iNPH)and Parkinson's disease(PD)patients.Methods:General clinical data and gait assessment results of 16 iNPH patients, 20 PD patients, and 23 healthy adults seeking treatment at Tianjin Huanhu Hospital between January 2020 and December 2020 were retrospectively analyzed.Gait analysis was conducted using the Mobility Lab? system with APDM Opal sensors from the US.Results:The 16 patients in the iNPH group had a mean age of(68.81±8.73), the 20 patients in the PD group had a mean age of(65.05±10.15), and the 23 adults in the control group had a mean age of(59.96±6.20).There was no significant difference in age between the iNPH group and the PD group( P>0.05).However, the iNPH group was older than the healthy control group( t=3.71, P<0.05).The disease duration of the iNPH group was(22.94±23.19)months, which was shorter than(92.60±53.70)months in the PD group( t=5.23, P<0.05).The mini-mental state examination(MMSE)score(17.13±7.08)and the Montreal Cognitive Assessment(MoCA)score(11.75±5.43)of the iNPH group were significantly lower than those in the PD group[(24.17±4.73), t=3.45, P<0.05、(21.29±5.82), t=4.86, P<0.05]and the control group[(26.70±1.61), t=5.31, P<0.05、(22.78±3.30), t=7.89, P<0.05].Compared with the PD group, the iNPH group had a significantly lower foot clearance[right: (1.65±0.76)cm vs.(2.56±1.30)cm]and smaller bilateral toe-off angles[left: (20.59±6.11)° vs.(28.43±6.36)°; right: (20.78±6.88)° vs.(28.12±7.49)°, t=3.74、3.02, respectively, all P<0.05].There were statistically significant differences in all gait parameters in iNPH patients compared with the control group( P<0.05). Conclusions:iNPH patients exhibit clear gait disturbance, which is more prominent than in PD patients.The wearable gait analysis system can accurately assess gait disorders in iNPH patients, and can be applied to gait assessment and the development of rehabilitation plans.

Objective:To investigate the efficacy and safety of selective dorsal rhizotomy with small incision under electrophysiological monitoring in lower limb spasticity.Methods:Twenty patients with lower limb spasticity due to craniocerebral injury admitted to Department of Neurosurgery,Tianjin Huanhu Hospital from January 2019 to December 2023 were selected. Target muscles (Ashworth Scale graded 1 + or higher) were identified preoperatively. Intraoperatively, the lower L 1 spinous process and the upper L 2 spinous process were resected to expose the cauda equina nerves. A bipolar stimulator was applied to electrically stimulate the cauda equina nerves root by root to identify the sensory nerves of the target muscles; subsequently, strings of electrical stimulation were given, 50% cauda equina nerves were cut off if no contraction of the contralateral muscles was seen, and 75% were cut off if contraction of the contralateral muscles was noted. Motor function and muscle tension were assessed and compared before and 6 months after surgery by Gross Motor Function Measure (GMFM)-66, Gross Motor Function Classification System (GMFCS), and Ashworth spasticity scale. Complications early after surgery and 6 months after surgery were observed. Results:The most common targeted muscles in these 20 patients included the gastrocnemius (the medial and lateral side, n=20), followed by the biceps femoris ( n=12) and the adductor muscles of thigh ( n=9). Number of nerves intraoperatively cut in patients with GMFCS grading 1-4 was 5.40±1.84, 9.50±6.36, 11.67±5.86, and 14.00±5.66, respectively, with significant differences ( F=5.506 , P=0.009). Grading of Ashworth spasticity scale of the target muscles before surgery in these 20 patients showed significant difference compared with that at 6 months after surgery ( P<0.05), and average rank indicated that Ashworth spasticity scale of target muscles 6 months after surgery was graded obviouly better than that before surgery. In addition, the GMFM-66 total scores and major joint motion scores of the patients 6 months after surgery were significantly higher than those before surgery ( P<0.05). Fifteen patients had fever early after surgery, 18 patients had incisional pain, and 1 patient developed reversible hypesthesia of the lower extremities; these symptoms disappeared 0.5-4.0 years after surgery. No patients developed lower limb hypokinesia, urinary and defecation disorders, or spinal deformities. Conclusion:Selective dorsal rhizotomy with small incision under electrophysiological monitoring used in this study can effectively reduce surgical trauma and relieve lower limb spasticity due to craniocerebral injury, enjoying high surgical safety.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Purpose: Drug resistance is one of the main causes of chemotherapy failure in patients with small cell lung cancer (SCLC), and extensive biological studies into chemotherapy drug resistance are required. Materials and Methods: In this study, we performed lncRNA microarray, in vitro functional assays, in vivo models and cDNA microarray to evaluate the impact of lncRNA in SCLC chemoresistance. Results: The results showed that KCNQ1OT1 expression was upregulated in SCLC tissues and was a poor prognostic factor for patients with SCLC. Knockdown of KCNQ1OT1 inhibited cell proliferation, migration, chemoresistance and promoted apoptosis of SCLC cells. Mechanistic investigation showed that KCNQ1OT1 can activate transforming growth factor-β1 mediated epithelial-to-mesenchymal transition in SCLC cells. Conclusion Taken together, our study revealed the role of KCNQ1OT1 in the progression and chemoresistance of SCLC, and suggested KCNQ1OT1 as a potential diagnostic and prognostic biomarker in SCLC clinical management.

Objective To explore the effect of motor imagery therapy combined with balance evaluation and training on balance and performance in the activities of daily living (ADL) after an initial stroke.Methods A total of 48 stroke patients were randomly divided into a control group (n =25) and an observation group (n =23).All of the patients in both groups were given routine rehabilitation and balance training.In addition,the patients of the observation group were given motor imagery therapy.Balance and ADL performance were assessed before the training and 2 weeks and 4 weeks after the training began.The subjects' balance was analyzed using the center of the gravity shift index,shift angle,total length of shift trace and envelope area using a balance evaluation system and the balance subscale of the Fugl-Meyer assessment (FM-B).Performance in the activities of daily living was assessed using the modified Barthel index (MBI).Results Before the training there were no significant differences between the two groups in terms of any of the measurements.After 2 weeks and 4 weeks of training,all the measurements in both groups were significantly better than those before training,but the improvement of the observation group was significandy greater than that of the control group (except in terms of the MBI).Conclusion Motor imagery therapy combined with balance training can distinctly improve the balance and activities of daily living of stroke survivors.The combination is worthy of application in the clinic.