Purpose To investigate the cortical thickness features in Parkinson's disease(PD)patients at various stages and their association with dopamine transporter(DAT)levels in the putamen.Materials and Methods We retrospectively enrolled 30 PD patients and 15 healthy subject who underwent 11C-CFT PET and T1 MRI scans at the Department of Nuclear Medicine/PET Center of Huashan Hospital from August 2016 to October 2020.DAT average radioactivity in the anterior and posterior putamen was analysis using SPM12 software,with the occipital lobe as the reference region.Cortical segmentation and reconstruction were performed on T1 images using Freesurfer v7.2.The differences in cortical thinning between the groups were compared using a general linear model.Additionally,the relationship between cortical thickness in various brain regions and DAT uptake in the putamen were assessed.Results Compared to healthy subjects,significant cortical thinning was observed in the left inferior parietal lobule and the right and left inferior middle frontal gyrus of PD patients(all P<0.05).There was a significant positive correlation between the cortical thickness of the left inferior parietal lobule and right inferior middle frontal gyrus and DAT uptake in the corresponding anterior/posterior parts of the putamen(r=0.30-0.47,all P<0.05).Furthermore,the DAT uptake in the right precentral gyrus was positively correlated with the ipsilateral posterior putamen,exhibiting a stronger correlation than on the contralateral side(r=0.32,P=0.029).Conclusion The results show that the thickness of the thinning cortex area in the PD patients correlates significantly positively with DAT levels in the putamen,highlighting the importance of the basal ganglia cortical circuit and providing a basis for further research into the neural mechanisms of PD.

AIM:This study aims to investigate the impact of TWIK-1 channels on abnormal pacemaker activi-ties induced by hypokalemia and to elucidate the underlying mechanisms.METHODS:The gene sequences encoding hu-man TWIK-1,specific TWIK-1 shRNA and TWIK-1-T118i mutant were synthesized and subsequently subcloned into lenti-viral vectors.To knock down the TWIK-1 gene in human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs),the cells were transduced with lentivirus carrying the specific TWIK-1 shRNA sequences.For the overexpression of TWIK-1 or the TWIK-1-T118i mutant in HL-1 mouse cardiomyocytes,the cells received lentiviral transduction containing the respective gene sequences.Patch-clamp techniques were employed to assess the effects of 1 mmol/L extracellular K+on the membrane potentials and whole-cell currents of the cardiomyocytes.RESULTS:Under conditions of 1 mmol/L extra-cellular K+,depolarization of membrane potentials was observed in the hiPSC-CMs and the HL-1 mouse cardiomyocytes ex-pressing human TWIK-1 channel,leading to the induction of abnormal pacemaker activities.This phenomenon could be reversibly abolished by the removal of extracellular Na+or inhibited through TWIK-1 knockdown.In contrast,the mem-brane potentials of HL-1 mouse cardiomyocytes expressing human TWIK-1-T118i mutant hyperpolarized,with no occur-rence of abnormal pacemaker activities.The hiPSC-CMs exhibiting abnormal pacemaker activities at 1 mmol/L extracellu-lar K+demonstrated TWIK-1-like Na+leak currents,which were blocked by quinine,a non-selective blocker of TWIK-1.CONCLUSION:The TWIK-1 channels play a critical role in the development of hypokalemia-induced abnormal pace-maker activities in human cardiomyocytes by facilitating Na+leak currents.

Objective:To investigate the application of pedicled or perforator flaps transfer in the stage Ⅰ tissue defect repair after vulvar cancer surgery.Methods:From January 2005 to December 2023, 20 patients with vulvar cancer who underwent extensive episiectomy or extended episiectomy±inguinal lymph node resection+vulvar defect flap transfer were collected in Huanxing Cancer Hospital of Chaoyang District and Cancer Hospital and Peking Union Medical College, Chinese Academy of Medical Sciences. The survival status, appearance structure, sexual function satisfaction, tumor recurrence, and survival were analyzed.Results:(1) The median age of the 20 patients was 59 years (ranged: 29-73 years). There were 14 patients with recurrence and 6 patients with initial treatment. Pathological types: 14 cases of squamous cell carcinoma, 4 cases of Paget′s disease, 1 case of malignant melanoma, 1 case of adenoid cystic carcinoma (salivary gland type carcinoma). (2) Among the 20 patients, 6 cases underwent extensive episiotomy and 14 underwent extended episiotomy (1 of them underwent extensive excision of inguinal masses). Simultaneous inguinal lymphadenectomy (or dissection) were performed in 11 cases, including 7 cases of bilateral inguinal lymph node resection (or dissection) and 4 cases of unilateral inguinal lymph node resection (or dissection). Flap source: pedicled flap in 12 cases, perforator flap in 8 cases. All the 20 patients were removed at 10-14 days after operation, and all of them survived with rosy skin color and good elasticity. Seventeen cases of transferred flaps healed at stage Ⅰ, 2 cases healed at about 6 weeks due to incision leakage, and 1 case healed at 6 weeks after incision infection debridement. Six months after the operation, 2 cases felt that the pubic mound was thick and swollen. The other 18 cases showed vulva fullness and elasticity, no displacement of urethral opening, no deviation of urethra during urination, no stenosis of vaginal opening, no vulvar scar pain. In addition to 1 unmarried 29-year-old patient and 6 patients over 65 years old who had no sexual life before and after surgery, the other 13 patients had normal sexual life after surgery. (3) The follow-up period were 6 to 100 months, and 9 cases (45%, 9/20) relapsed during the follow-up period. There were 5 deaths (25%, 5/20), who were due to recurrence of vulvar cancer. The 5-year survival rate of 20 patients was 75%, including 83% in 6 patients with initial treatment and 71% in 14 patients with recurrence and reoperation.Conclusions:The combination of flap transfer for episioplasty with vulvar cancer surgery does not affect the wound healing. Because the external structure of the vulva is repaired, it could effectively improve the local wound healing ability and improve the organ function, and has good clinical application value.

Objective·To construct and validate a nomogram for distinguishing primary Sj?gren's syndrome(PSS)from immunoglobulin G4-related sialadenitis(IgG4-RS)based on ultrasound scoring parameters and clinical indicators.Methods·A total of 141 patients with PSS and 31 patients with IgG4-RS were retrospectively recruited from Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from January 2018 to December 2023.The ultrasound scoring parameters,including parotid gland ultrasound(PGUS)score,submandibular gland ultrasound(SMGUS)score,and salivary gland ultrasound(SGUS)score,along with clinical indicators such as gender,age,anti-SSB/La antibody,anti-SSA/Ro60 antibody,anti-SSA/Ro52 antibody,IgG,and rheumatoid factor(RF),were collected.The optimal US scoring parameters and clinical indicators were screened by least absolute shrinkage and selection operator(LASSO)regression,and a nomogram model was constructed to distinguish PSS from IgG4-RS.The internal validation of the model was carried out through bootstrap method.Receiver operator characteristic(ROC)curve,calibration curve and decision curve analysis(DCA)were used to estimate the discrimination,calibration,and clinical utility of the nomogram model,respectively.Results·LASSO regression identified six major variables:gender,age,anti-SSA/Ro60 antibody,anti-SSA/Ro52 antibody,PGUS score,and SMGUS score.These variables were used to construct the nomogram.ROC curve of the nomogram showed that the area under the curve(AUC)was 0.976,indicating the nomogram had strong discrimination ability.The bootstrap method was used for internal validation with 1 000 resampling iterations,and the average absolute error was 0.018.Calibration curve demonstrated good agreement between predicted and observed values.DCA indicated that the nomogram had certain clinical utility.Conclusion·The nomogram based on ultrasound scoring parameters and clinical indicators demonstrates excellent discrimination and calibration in differentiating PSS from IgG4-RS.It has the potential to assist in clinical diagnosis and decision-making.

Objective·To construct a nanoengineered T cell system and explore its synergistic efficacy in the in vitro treatment of oral squamous cell carcinoma,and provide a new strategy for this disease.Methods·Zr-MOF nanoparticles with a highly hydrophilic hyaluronic acid(HA)coating(PCN224-HA NPs)were prepared,and their carboxyl groups were activated to enable coupling with anti-CD45 antibodies through an amide reaction.High-purity CD8+T cells were then extracted from the spleens of mice,and the PCN224-HA NPs were loaded onto the T cells via the CD45 antigens on their surface.The coupling was observed using bioelectron microscopy and confocal microscopy,and free radical generation was detected under ultrasound irradiation.The viability of Cal27 cells was recorded by a microplate reader to explore therapeutic effects in vitro.Results·PCN224-HA NPs were successfully synthesized and confirmed to be coupled onto the surface of CD8+T cells,constructing a nanoengineered T cell system(T cells@PCN224-HA NPs).Free radical production was monitored after ultrasound irradiation and the viability of Cal27 cells decreased to 31.70%after in vitro treatment.Conclusions·Preliminary experiments demonstrated that the nanoparticles can be successfully loaded onto the surface of T cells,providing combined sonodynamic therapeutic effects from the nanoparticles and immunocidal effects from the T cells.This offers a novel strategy for the treatment of oral squamous cell carcinoma,with potential for further in vivo anti-tumor experiments and therapeutic applications.

Objective: To understand the moderating effect of cohabitation with parents on the association between peer dating behavior and sexual behaviors among secondary vocational school students, so as to provide a scientific basis for preventing sexual behaviors among secondary vocational school students. Methods: From March to April 2021, an electronic questionnaire survey was conducted among 3 180 students from 6 vocational schools in Shanghai (urban, suburban, exurban) and Shaanxi (Shangluo, Ankang, Baoji) using cluster sampling. Spearman correlation analysis was used to investigate the relationship of cohabitation with parents, peer dating behavior and sexual behaviors among secondary vocational school students. Binary Logistic regression analysis was performed to investigate the role of cohabitation with parents on peer dating behavior and sexual behaviors among secondary vocational students. Results: There was a significant negative between cohabitation with parents and sexual ( r =-0.04); and there was a positive correlation between peer dating behavior and sexual behaviors ( r =0.24), as well as cohabitation with parents and peer dating behavior ( r =0.04)( P <0.05). Multivariable Logistic regression analysis showed an association between peer dating behavior and the occurrence of sexual behaviors ( OR=2.79-12.95, P <0.05). Cohabitation with parents played a moderating role in the association between peer dating behavior and sexual behaviors, and a signification interaction was found between cohabitation with parents and reporting that a small part or about half of their peers had dating behavior ( OR =0.48, P <0.05). Conclusions The more peers dating behavior are associated with a higher risk of sexual behaviors among secondary vocational school students, and cohabitation with parents can partly reduce this risk. School and family sexuality education for secondary vocational students should be strengthened to improve their interpersonal skills and decision-making, and ability to resist peer pressure, so as to reduce their risk of sexual behaviors.

Objective To exploring the expression of microRNA-93-5p(miRNA-93-5p)and neuregulin protein 1(NRG1)in thyroid cancer tissues and their relationship with clinicopathological characteristics and survival prognosis.Methods Frozen tissue specimens of 136 patients with thyroid diseases who underwent surgical treatment in the hospital from January 2018 to May 2020 were selected,including 84 cases of thyroid cancer(thyroid cancer group),52 cases of benign thyroid diseases(benign thyroid disease group),and another 40 cases of normal thyroid tissues(control group).The relative expression levels of miRNA-93-5p and the positive expression rate of NRG1 in the tissues of the thyroid cancer group,the benign thyroid disease group and the control group were compared,and the relationship between the expression of miRNA-93-5p and NRG1 in patients with thyroid cancer and the clinicopathological characteristics was analyzed.Multivariate Logistic regression was used to analyze the influencing factors of miRNA-93-5p and NRG1 expression.Kaplan-Meier survival curve was used to analyze the relationship between the expression of miRNA-93-5p and NRG1 and survival prognosis in patients with thyroid cancer.Results There were statistically significant differences in the relative expression levels of miRNA-93-5p and the positive expression rate of NRG1 among the thyroid cancer group,the benign thyroid disease group and the control group(P＜0.05).The relative expression level of miRNA-93-5p in thyroid cancer tissues was negatively correlated with the positive expression rate of NRG1(r=-0.216,P=0.013).The proportion of tumor maximum diameter＞1 cm,the rate of moderate and low differentiation,the rate of capsular invasion,the rate of lymphatic metastasis,and the proportion of TNM stage Ⅲ+Ⅳ in the miRNA-93-5p high-expression group were higher than those in the miRNA-93-5p low-ex-pression group(P＜0.05),and the above indicators in the NRG1 high-expression group were all lower than those in the NRG1 low-expression group(P＜0.05).Multivariate Logistic regression analysis revealed that the maximum diameter of the tumor,degree of differentiation,capsular invasion,lymphatic metastasis and TNM stage were all influencing factors for the expression of miRNA-93-5p and NRG1.The 3-year cumulative survival rate of the miRNA-93-5p high-expression group was lower than that of the miRNA-93-5p low-expres-sion group(P＜0.05),and the 3-year cumulative survival rate of the NRG1 high-expression group was higher than that of the NRG1 low-expression group(P＜0.05).Conclusion In thyroid cancer tissues,miRNA-93-5p is highly expressed and NRG1 is lowly expressed.Both can be used as biomarkers for evaluating the survival prognosis of patients.

AIM:This study aims to investigate the impact of TWIK-1 channels on abnormal pacemaker activi-ties induced by hypokalemia and to elucidate the underlying mechanisms.METHODS:The gene sequences encoding hu-man TWIK-1,specific TWIK-1 shRNA and TWIK-1-T118i mutant were synthesized and subsequently subcloned into lenti-viral vectors.To knock down the TWIK-1 gene in human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs),the cells were transduced with lentivirus carrying the specific TWIK-1 shRNA sequences.For the overexpression of TWIK-1 or the TWIK-1-T118i mutant in HL-1 mouse cardiomyocytes,the cells received lentiviral transduction containing the respective gene sequences.Patch-clamp techniques were employed to assess the effects of 1 mmol/L extracellular K+on the membrane potentials and whole-cell currents of the cardiomyocytes.RESULTS:Under conditions of 1 mmol/L extra-cellular K+,depolarization of membrane potentials was observed in the hiPSC-CMs and the HL-1 mouse cardiomyocytes ex-pressing human TWIK-1 channel,leading to the induction of abnormal pacemaker activities.This phenomenon could be reversibly abolished by the removal of extracellular Na+or inhibited through TWIK-1 knockdown.In contrast,the mem-brane potentials of HL-1 mouse cardiomyocytes expressing human TWIK-1-T118i mutant hyperpolarized,with no occur-rence of abnormal pacemaker activities.The hiPSC-CMs exhibiting abnormal pacemaker activities at 1 mmol/L extracellu-lar K+demonstrated TWIK-1-like Na+leak currents,which were blocked by quinine,a non-selective blocker of TWIK-1.CONCLUSION:The TWIK-1 channels play a critical role in the development of hypokalemia-induced abnormal pace-maker activities in human cardiomyocytes by facilitating Na+leak currents.

The efficient production of L-glutamate is dependent on the product's rapid efflux, hence researchers have recently concentrated on artificially modifying its transport system and cell membrane wall structure. Considering the unique composition and structure of the cell wall of Corynebacterium glutamicum, we investigated the effects of CmpLs on L-glutamate synthesis and transport in SCgGC7, a constitutive L-glutamate efflux strain. First, the knockout strains of CmpLs were constructed, and it was confirmed that the deletion of CmpL1 and CmpL4 significantly improved the performance of L-glutamate producers. Next, temperature-sensitive L-glutamate fermentation with the CmpL1 and CmpL4 knockout strains were carried out in 5 L bioreactors, where the knockout strains showcased temperature-sensitive characteristics and enhanced capacities for L-glutamate production under high temperatures. Notably, the CmpL1 knockout strain outperformed the control strain in terms of L-glutamate production, showing production and yield increases of 69.2% and 55.3%, respectively. Finally, the intracellular and extracellular metabolites collected at the end of the fermentation process were analyzed. The modification of CmpLs greatly improved the L-glutamate excretion and metabolic flux for both L-glutamate production and transport. Additionally, the CmpL1 knockout strain showed decreased accumulation of downstream metabolites of L-glutamate and intermediate metabolites of tricarboxylic acid (TCA) cycle, which were consistent with its high L-glutamate biosynthesis capacity. In addition to offering an ideal target for improving the stability and performance of the industrial strains for L-glutamate production, the functional complementarity and redundancy of CmpLs provide a novel target and method for improving the transport of other metabolites by modification of the cell membrane and cell wall structures in C. glutamicum.
Corynebacterium glutamicum/genetics* ; Glutamic Acid/biosynthesis* ; Fermentation ; Metabolic Engineering ; Bacterial Proteins/metabolism* ; Bioreactors/microbiology* ; Gene Knockout Techniques