Alzheimer’s disease (AD) is one of the most common and severe dementias, severely affecting the physical and mental health and quality of life of patients and imposing a heavy burden on society. Recently, transcranial electrical stimulation (tES) has shown great potential for improving cognitive function in AD. Transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) are the two main forms of tES. The present review mainly summarizes the neuromolecular mechanisms of tDCS and tACS for the improvement of AD. Both techniques show similarities in exerting neuroprotective effects, improving cerebral blood flow to alleviate cerebrovascular dysfunction, affecting the state and function of astrocytes, affecting the levels of amyloid β‑protein (Aβ) and phosphorylated tau (p-tau) proteins, and affecting neuroplasticity. Specifically, tDCS improves neuronal status, inhibits neuronal apoptosis, improves cholinergic neurons and reduces oxidative stress, etc., and further exerts neuroprotective effects, but tACS mainly maintains the normal function of cholinergic neurons to exert the effects. For the alleviation of cerebrovascular dysfunction, tDCS has particular advantages in optimizing the neural vascular unit and improving the blood-brain barrier. For astrocytes, tDCS attenuates inflammatory responses by inhibiting their activation. In contrast, the effect of tACS on the activation state of microglial cells is still controversial for enhancement in AD mice and inhibition in patients. For Aβ levels, the effects of tDCS in AD patients are also inconclusive, but in AD rodents, tDCS may regulate molecular pathways related to Aβ production and degradation, thereby removing Aβ. In addition, tACS reduces p-tau levels in AD patients, but tDCS shows a trend toward reduction. In short, the effect of tES on Aβ and p-tau needs further investigation. Regarding neuroplasticity, tDCS improves cortical and synaptic plasticity, but tACS improves only synaptic plasticity. However, both techniques do not affect the molecular level associated with plasticity. On the other hand, this review has summarized some interesting findings of tES in non-AD rodents that may be relevant to the pathological mechanisms of AD. For neuroprotection, tDCS can promote neurogenesis, GABAergic and glutamatergic neurotransmission, modulate neuroprotection-related signaling pathways, reduce oxidative stress, and protect hippocampal neurons. In addition, tDCS inhibits conversion of microglia to the M1 phenotype and promotes conversion to the M2 phenotype, thereby reducing neuroinflammation. Importantly, tDCS induces changes in molecular indices associated with synaptic plasticity. These findings in non-AD rodents provide a reference for understanding the potential effect and possible mechanism of tES in AD and for exploring new approaches to treat other diseases with similar pathological features. In addition, tES has shown some effects in AD rodents, such as tACS improving plasticity, that have not been studied in non-AD rodents. These effects suggest the particular complexity of the pathological mechanisms of AD, which should be considered when applying the results of tES studies in non-AD rodents to AD rodents. In conclusion, this review provides a comprehensive overview of the neuromolecular mechanisms of tES in AD research and highlights its promise as a non-invasive brain stimulation technique in the treatment of AD. Furthermore, tES will play an indispensable role in the treatment of neuropsychiatric disorders and in the study of brain function.

OBJECTIVE To analyze chemical components of Yao ethnic medicine Pittosporum pauciflorum， establish its fingerprint and investigate the spectrum-effect relationship of its anti-inflammatory effect. METHODS UHPLC-Q-Orbitrap-MS technology was used to analyze the chemical components of P. pauciflorum （batch S6）. The fingerprints for 10 batches of P. pauciflorum from different producing areas in Guangxi Province （batches S1-S10） were established by HPLC， and similarity assessment and chemometric pattern recognition analysis were conducted. RAW264.7 inflammatory cell model was induced by lipopolysaccharide， and the anti-inflammatory activity of P. pauciflorum was investigated. Using inhibition rates of nitric oxide （NO）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β as efficacy indicators， grey relational analysis and partial least squares regression analysis were adopted to evaluate the spectrum-effect relationship of the anti-inflammatory effect of P. pauciflorum. RESULTS There were 60 chemical components， including flavonoids， phenolic acids， lipids， etc.， identified in P. pauciflorum. The fingerprints for 10 batches of P. pauciflorum showed 14 common peaks，with similarity values ranging from 0.883 to 0.991. Three common peaks were assigned neochlorogenic acid （peak 5）， chlorogenic acid （peak 7）， and syringaldehyde （peak 10）. The classification results of the systematic clustering analysis and the principal component analysis were basically consistent. Batches S1 to S10 of P. pauciflorum significantly reduced the levels of NO， TNF-α， IL-6 （except for batch S5） and IL-1β in the cell supernatant （P＜0.05 or P＜0.01）. Inhibition rates of above inflammatory indexes were 10.26%-39.96%， 14.96%-31.36%， 1.38%-21.27%， 18.54%-28.00%， respectively. The contents of neochlorogenic acid， syringaldehyde， as well as the components corresponding to peaks 1， 3， 9， 12 and 14，exhibited a strong correlation with the anti-inflammatory effects of P. pauciflorum. CONCLUSIONS The present study has analyzed the chemical components of P. pauciflorum and established HPLC fingerprints for 10 batches of P. pauciflorum. Each batch of medicinal herbs demonstrates certain anti- inflammatory activities， among which neochlorogenic acid， syringaldehyde， and the components corresponding to peaks 1， 3， 9， 12 and 14 are likely to be the active anti-inflammatory components.

Objective To investigate the regulatory role of the programmed cell death protein 1 (PD-1) and its ligand programmed cell death protein ligand 1 (PD-L1) signaling on the subtypes and functions of natural killer (NK) cells at the maternal-fetal interface during the second trimester in mice following Toxoplasma gondii infection during the first trimester. Methods Twelve 6- to 8-week-old female mice of the C57BL/6J strain were divided into a control group and an infection group, of 6 mice in each group. On the 6.5th day of pregnancy (Gd6.5), each pregnant mouse in the infection group was intraperitoneally injected with 150 tachyzoites of the Toxoplasma gondii PRU strain, while mice in the control group were injected with an equal volume of physiological saline. On the 12.5th day of pregnancy (Gd12.5), uterus and placenta tissues were sampled from pregnant mice for pathological observations, and the mRNA expression levels of PD-1, PD-L1, and tumor necrosis factor-α (TNF-α) were quantified in uterus and placenta tissues. The PD-1 and DX5 expression was measured on NK cells at the maternal-fetal interface using flow cytometry. In addition, the in vitro JEG-3 trophoblast cells and NK-92MI cells co-culture system was established as the control group, and the addition of T. gondii tachyzoites in the co-culture system served as the infection group. The PD-1, PD-L1, and DX5 mRNA expression was quantified in cells using real-time fluorescence quantitative reverse transcription PCR (RT-qPCR) assay, and the TNF-α concentration was measured in the cell culture supernatant using enzyme-linked immunosorbent assay (ELISA). Results On Gd12.5, clear and intact cellular structures of placental decidual tissues were seen in pregnant mice in the control group, with no remarkable abnormal changes found in the uterine columnar epithelial cells, and inflammatory cell infiltration and blood stasis at varying degrees were found in uterine and placental tissues from pregnant mice in the infection group. The relative PD-1, PD-L1, and TNF-α mRNA expression was (1.004 ± 0.004), (1.001 ± 0.001), and (1.001 ± 0.001) in uterine tissues from pregnant mice in the control group and (2.480 ± 0.720), (3.355 ± 0.920), and (2.391 ± 0.073) in the infection group, respectively. The relative PD-1, PD-L1, and TNF-α mRNA expression was (1.007 ± 0.010), (1.006 ± 0.006), and (1.001 ± 0.001) in the uterine tissues in the control group and (6.948 ± 1.918), (3.225 ± 1.034), and (1.536 ± 0.150) in the infection group, respectively. The relative PD-1, PD-L1, and TNF-α mRNA expression was higher in both the uterine (t = 3.55, 4.43 and 33.02, all P values < 0.05) and placental tissues (t = 5.36, 3.72 and 6.18, all P values < 0.05) in the infection group than in the control group. Flow cytometry showed that the proportions of PD-1⁺ NK cells, PD-1⁺ DX5⁺ NK cells, and DX5⁺ NK cells were (12.200 ± 1.082)%, (9.373 ± 7.728)%, and (44.000 ± 4.095)% in uterine tissues from pregnant mice in the control group, and (21.733 ± 1.630)%, (18.767 ± 1.242)%, and (73.367 ± 0.611)% in the infection group, respectively. The proportions of PD-1⁺ NK cells, PD-1⁺ DX5⁺ NK cells, and DX5⁺ NK cells were (1.100 ± 0.510)%, (2.277 ± 1.337)%, and (96.167 ± 2.831)% in placental tissues from mice in the control group, and (26.867 ± 9.722)%, (23.433 ± 6.983)%, and (82.467 ± 2.248)% in the infection group, respectively. The proportions of PD-1⁺ NK cells (t = 8.45, P < 0.05) and DX5⁺ NK cells (t = 12.29, P < 0.05) were higher in uterine tissues from pregnant mice in the infection group than in the control group, and no significant difference was seen in the proportion of PD-1⁺ DX5⁺ NK cells (Z = -1.09, P > 0.05). The proportions of PD-1⁺ NK cells (t = 4.58, P < 0.05) and PD-1⁺ DX5⁺ NK cells (t = 5.15, P < 0.05) were higher in placental tissues from pregnant mice in the infection group than in the control group, while the proportion of DX5⁺ NK cells was lower in the infection group than in the control group (t = -6.56, P < 0.05). RT-qPCR assay revealed that the relative PD-1, PD-L1, and DX5 mRNA expression was (1.010 ± 0.005), (1.002 ± 0.003), and (1.001 ± 0.001) in the JEG-3 cells and NK92MI cells co-culture system and (3.638 ± 1.258), (0.397 ± 0.158), and (4.267 ± 1.750) in the control group, and ELISA measured that the TNF-α concentration was higher in the cell culture supernatant in the infection group [(22.056 ± 3.205) pg/mL] than in the control group [(12.441 ± 0.001) pg/mL] (t = 5.20, P < 0.05). The PD-1(t = 3.62, P < 0.05) and DX5 mRNA expression (t = 3.23, P < 0.05) was higher in the infection group than in the control group, and the PD-L1 mRNA expression was lower in the infection group than in the control group (t = -6.63, P < 0.05). Conclusions Following T. gondii infection, both PD-L1 expression and PD-1 expression on DX5⁺ NK cells at the maternal-fetal interface are upregulated in mice during the second trimester; however, the proportion of DX5⁺ NK cells decreases. These findings suggest that PD-1/PD-L1 signaling may suppress NK cell functions by modulating DX5⁺ NK cell subsets.

Objective To investigate the clinical effect of orthopedic robot combined with Starr pelvic reduction frame in the treatment of Tile type C pelvic ring fracture.Methods From October 2019 to May 2021,14 patients with type C pelvic ring fracture were treated with robotic combined with Starr pelvic reduction frame,including 9 males and 5 females.The age ranged from 33 to 69 years.All the 14 patients had fresh closed fractures without femur,tibia and fibula fracture.Surgery was complet-ed from 4 to 7 d after hospital admission.During the operation,the X-ray carbon bed was used,the pelvic ring was reduced by Starr pelvis reduction frame,and pelvic ring fracture was treated by orthopedic robot.Operation time,bleeding volume,fluo-roscopy times of single screw placement,fracture reduction quality,affected limb function and complications were observed.Radiological reduction was evaluated using Matta scoring standard,and clinical efficacy was evaluated by Majeed pelvic func-tion scoring system at the final follow-up.Results All of 14 patients successfully completed the operation,the operation time was 84 to 141 min,the bleeding volume was 20 to 50 ml,and the fluoroscopy times of single screw insertion was 4 to 9 times.All of 14 patients were followed up for 12 to 24 months.The healing time was 3 to 7 months.No complications such as fracture of internal fixation,screw loosening,infection and nerve injury were found.According to the evaluation criteria of Matta imag-ing reduction,9 cases were excellent,4 cases were good,and 1 case was fair.At the final follow-up,Majeed pelvic function scoring system was used:10 cases were excellent,4 cases were good.Conclusion The treatment of type C pelvic ring fracture with robotic combined Starr pelvis reduction frame is simple,time-saving,less trauma,less complications and effective.

To investigate the role of the nucleotide-binding domain and leucine-rich-repeat-contai-ning family member X1(NLRX1)in the replication of Newcastle disease virus(NDV),the ex-pression level of NLRX1 was examined following infection of 10-day-old specific pathogen-free(SPF)chicks and HD11 cells with the NDV NA-1 strain.Additionally,the proliferation of NDV,the expression of pro-inflammatory cytokines in HD11 cells,and the oxidative stress status were e-valuated in the presence of either overexpressed or underexpressed NLRX1.The results demonstra-ted that NA-1 infection led to an increase in NLRX1 expression both in vivo and in vitro.Further-more,overexpression of NLRX1 inhibited viral proliferation,enhanced the expression of cellularIL-1β,IL-6,and IFN-β,without affecting levels of autophagy or apoptotic cells.However,NLRX1 elevation resulted in elevated mRNA levels of iNOS,Keap1,Nrf2,NQO1,and HO-1 within 24 h.In conclusion,NLRX1 suppresses NDV proliferation by promoting early ROS production.

Objective To explore the differences in scapular motion and shoulder function between patients suffering from rotator cuff tears(RCT)with and without type Ⅲ scapular dyskinesis(SD).Meth-ods Between September 2021 and March 2023,sixteen patients suffering from rotator cuff tears with SD(SD group)and 17 counterparts without SD(non-SD group)were recruited from the Sports Hospital of the General Administration of Sport of China.Their scapular motion was assessed by measuring three parameters in the X-rays,including scapular spine line(LSS),scapular upward rotation angle(SU-RA),and coracoid upward shift distance(CUSD).Moreover,their shoulder range of motion in flexion,abduction and external rotation were recorded,and further evaluated using the Pain Visual Analog Scale(VAS)and American Shoulder and Elbow Surgeons Score(ASES).Results No significant differenc-es were found between the two groups in the average score of SURA,CUSD and LSS at 0°～30° shoul-der abduction,or in that of CUSD and LSS at 60°～90°shoulder abduction.However,the average SU-RA score of the SD group at 60°～90°shoulder abduction was significantly greater than the other group(P<0.05).The shoulder ranges of motion during active flexion,abduction and external rotation were significantly smaller in the SD group than in the non-SD group(P<0.05).Moreover,the average VAS score in the SD group was significantly higher than the non-SD group(P<0.05),while the average ASES score was significantly lower than the latter group(P<0.05).Conclusions RCT patients type III SD exhibits greater scapular upward rotation during shoulder abduction compared to those without SD.Moreover,the former patients suffer from more severe pain and have worse shoulder range of motion and functional performance than the latter.

Objective:To investigate the clinical features of 17q12 microdeletion cases before and after delivery, and provide a reference for prenatal diagnosis and genetic counseling.Methods:A retrospective analysis was conducted on five fetuses diagnosed with 17q12 microdeletion by single nucleotide polymorphism array in Quanzhou Women's and Children's Hospital between April 2020 and June 2023. Clinical data including prenatal ultrasonography findings, genetic causes, parental clinical features, and postnatal outcomes were summarized and analyzed using descriptive statistical analysis.Results:The five fetuses had normal results of karyotype analysis of amniotic fluid, but carried a microdeletion of 1.4 to 1.8 Mb in the 17q12 region of the chromosome, involving 20 genes listed in the Online Mendelian Inheritance in Man database. Pedigree verification was performed on all five cases and the results indicated one maternally inherited case with the mother having polycystic kidneys complicated by left hydronephrosis, one de novo case, and three paternally inherited cases with one father having multiple cysts in both kidneys and two fathers showing no abnormalities. Multiple abnormalities were found in the five fetuses by prenatal ultrasonography, including enhanced renal parenchymal echogenicity in four cases and pyelectasis in one case. Two cases chose to terminate the pregnancies, while the other three continued the pregnancies to full term. Postnatal follow-ups showed that one case was normal in growth and development with no abnormalities by renal ultrasound; one case developed polycystic kidney; one case with normal renal ultrasound findings had a speech disorder and symptoms of suspected autism at the age of three. Conclusions:The main manifestation of 17q12 microdeletion is enhanced renal parenchymal echogenicity in the fetal stage and postnatal polycystic kidney. In prenatally diagnosed cases, pedigree verification is necessary as an objective and scientific genetic counseling is helpful in pregnancy decision-making.

Occupational exposure limits for hazardous agents in the workplace—Part 1: Chemical hazardous agents (GBZ 2.1—2019) has been implemented since April 1, 2020. The document redefines the evaluation of occupational exposure by introducing a "reduction factor" to adjust the occupational exposure limits of chemical hazardous agents for long working hour systems to ensure a protection level reasonable for the workers and equivalent to conventional occupational exposure limits. This paper discussed common problems encountered in the context of using this adjustment strategy, such as the adjustment being unable to cover all working hours, and the adjustment of values of terms associated with occupational exposure limits. Corresponding solutions were proposed. Working cycle and average exposure time of each working cycle were introduced to evaluate the actual working hours of workers. Regarding involved terms, adjustments of their corresponding values were clarified according to their definitions and application scenarios. Examples were provided for occupational health service providers so that their occupational health practices could be carried out in a more scientific and reasonable manner.

Objective To summarize and analyze the preliminary clinical outcomes of the KokaclipTM transcatheter edge-to-edge mitral valve repair system for severe degenerative mitral regurgitation (DMR). Methods This study was a single-arm, prospective, single-group target value clinical trial that enrolled patients who underwent the KokaclipTM transcatheter edge-to-edge repair (TEER) system for DMR in the Department of Heart Surgery of Guangdong Provincial People's Hospital, Guangdong Cardiovascular Institute from June 2022 to January 2023. Differences in the grade of mitral regurgitation (MR) during the perioperative and follow-up periods were compared, and the incidences of adverse events such as all-cause death, thoracotomy conversion, reoperation, and severe recurrence of MR during the study period were investigated. Results The enrolled patient population consisted of 14 (50.0%) females with a mean age of 70.9±5.4 years. Twenty-eight (100.0%) patients were preoperatively diagnosed with typeⅡ DMR, with a prolapse width of 12.5 (11.0, 16.1) mm, a degree of regurgitation 4+ leading to pulmonary venous reflux, and a New York Heart Association cardiac function class≥Ⅲ. All patients completed the TEER procedure successfully, with immediate postoperative improvement of MR to 0, 1+, and 2+ grade in 2 (7.1%), 21 (75.0%), and 5 (17.9%) patients, respectively. Mitral valve gradient was 2.5 (2.0, 3.0) mm Hg. Deaths, thoracotomy conversion, or device complications such as unileaflet clamping, clip dislodgement, or leaflet injury were negative. Twenty-eight (100.0%) patients completed at least 3-month postoperative follow-up with a median follow-up time of 5.9 (3.6, 6.8) months, during which patients had a mean MR grade of 1.0+ (1.0+, 2.0+) grade and a significant improvement from preoperative values (P<0.001). There was no recurrence of ≥3+ regurgitation, pulmonary venous reflux, reoperation, new-onset mitral stenosis, or major adverse cardiovascular events. Twenty-two (78.6%) patients’ cardiac function improved to classⅠorⅡ. Conclusion The domestic KokaclipTM TEER system has shown excellent preliminary clinical results in selected DMR patients with a high safety profile and significant improvement in MR. Additional large sample volume, prospective, multicenter studies, and long-term follow-up are expected to validate the effectiveness of this system in the future.

Objective To evaluate the value of magnetic resonance imaging(MRI)in prenatal diagnosis of fetal Chiari malformation.Methods The prenatal MRI findings of 27 cases of Chiari malformation confirmed by follow-up in Obstetrics and Gynecology Hospital,Fudan University from Feb 2010 to Feb 2022 were retrospectively analyzed and compared with ultrasound findings.Results Twenty-seven pregnant women,aged from 16-36 years(average 28.0 years)and 27 fetuses with gestation from 15.3-38.4 weeks(average 24.3 weeks)were studied.There were 18 cases of Chiari Ⅱ(Chiari malformation type Ⅱ,CMⅡ),3 cases of Chiari Ⅲ(CMⅢ),6 cases of Chiari Ⅳ(CMⅣ).CMⅡ and CMⅢ images showed brain herniation,descending pons,narrowing or disappearance of the posterior fossa cistern and the fourth ventricle,the subarachnoid space disappears.There were 17 cases of hydrocephalus,2 cases of cerebrospinal fluid loss,17 cases of"lemon head"and"banana cerebellar"signs,4 cases of encephalocele,15 cases of spinal bifida,3 cases of lower spinal cord and 2 cases of spinal cavity,4 cases of spinal angular deformity and 6 cases of other malformations.In CMⅣ,there were 2 cases of undeveloped cerebellum and 4 cases of cerebellum and brainstem dysplasia,hydrocephalus in 5 cases,posterior fossa cistern widening in 4 cases,and other malformations in 4 cases.MRI showed the posterior fossa structure and spinal cord more clearly than ultrasound,and could find lesions not detected by ultrasound.Conclusion Prenatal MRI can be used as a complementary examination of ultrasound,which can improve the accuracy of diagnosis of Chiari malformation,reduce the rate of missed diagnosis,and clarify the classification of Chiari malformation.