Objective:To investigate the differences of comprehensively curative effect of neuro navigation system(NNS)-guided minimally invasive puncture(MIP)and conventional craniotomy hematoma evacuation(CHE)in treatment for traumatic intracerebral hemorrhage,and analyze the mechanisms of affecting the differences of the trajectories postoperative neurologically functional recovery between two kinds of surgical methods.Methods:Based on the design of multicenter prospective cohort study,a total of 240 patients with traumatic intracerebral parenchymal hemorrhage,who admitted to the Neurosurgery Center of Rugao Hospital of Traditional Chinese Medicine between June 2021 and May 2024,were selected.They were randomized into the NNS group(n=120)and the CHE group(n=120)by using a stratified block randomization method.The NNS group underwent NNS-guided surgical intervention,while the CHE group received conventional craniotomy.The primary endpoint was hematoma evacuation rate at the postoperative 7th day.The secondary endpoints encompassed surgical parameters,complications,and the prognostic indicators of function.Microstructural assessment was performed by using three-dimensional image fusion technique[three-dimensional-T1weighted imaging magnetic resonance imaging(3D-T1WI MRI)combined with thin-slice computed tomography(CT)]and tract-based spatial statistics(TBSS).Results:At the dimension of hematoma evacuation,the average hematoma evacuation rate of NNS group was(88.37±6.52)%at the postoperative 7th day,which was significantly higher than(76.15±10.32)%of CHE group,and the residual hematoma volume of NNS group was(5.23±2.15)mL at the postoperative 7th day,which was less than(11.49±4.78)ml,and the differences of them between two groups were significant(t=9.843,7.015,P<0.05),respectively.The surgical trauma parameters appeared polarization:the mean incision length in the NNS group was(3.15±0.73)cm,which reduced 76.3%of(13.24±2.15)cm of the CHE group,with statistically significant difference(Z=15.327,P<0.05).The operative duration of NNS group was(68.34±15.32)min,which was shorter than(142.56±23.48)min,and the difference was significant(t=29.846,P<0.05).The radiation dose of NNS group was(312.45±85.32)cGy·cm2,which was significantly higher than(45.23±12.15)cGy·cm2 of CHE group,and the difference was significant(Z=24.156,P<0.05).The volume of intraoperative blood transfusion of NNS group was(50.34±25.36)ml,which was significantly less than(325.67±158.32)ml,and the difference was significant(Z=18.943,P<0.05),The result of complication genealogy analysis indicated that the re-bleeding incidence of the NNS group was 6.67%,which decreased by 9.16%than 15.83%of the CHE group,and the difference of that between two groups was statistical significance(x2=5.627,P<0.05).However,there was not significant difference in infection rates and incidences of deep vein thrombosis between the two groups(P>0.05).For functional recovery,the proportion of patients whose modified Rankin Scale(mRS)scores was≤2 at the postoperative 90th day was 52.50%in the NNS group,which increased 13.33%than 39.17%in the CHE group,and the difference of that between two groups was statistical significance(x2=4.302,P<0.05).Additionally,the improvement value of National Institutes of Health Stroke Scale(NIHSS)was(9.34±4.156)in the NNS group,which existed marginal advantage of 2.19 points than(7.15±5.327)of the CHE group,and the difference was significant between two groups(Z=3.842,P<0.05).Conclusion:NNS-guided MIP appears notable advantages in enhancing hematoma evacuation efficiency and improving prognosis of neurological function.However,its increased amount of radiation exposure,and risks of specific complication should be considered.The craniotomy approach remains indispensable for complex hematoma morphologies.

Objective:To construct and validate a nomogram prediction model for the recurrence of common bile duct stones after endoscopic retrograde cholangiopancreatography (ERCP) in patients with common bile duct stones.Methods:The clinical data of 515 patients with common bile duct stones treated in Yancheng First People's Hospital from January 2018 to December 2022 were retrospectively analyzed, including 273 males and 242 females, aged (65.5±12.1) years. According to the ratio of 8∶2, all cases were randomly divided into a training set ( n=412) and a validation set ( n=103). According to whether common bile duct stones recurred after ERCP, 412 patients in the training set were divided into two groups: the recurrence group ( n=72) and the non-recurrence group ( n=340). The patients' gender, age, length and diameter of stones, number of stones, diameter of common bile duct and other clinical data were recorded. The logistic regression model was used to analyze the risk factors of recurrence, and a nomogram was constructed based on the analysis results. The concordanceindex, area under the receiver operating characteristic (ROC) curve and calibration chart were used to evaluate the model. Bootstrap self sampling method was used to internally verify the prediction model. Results:The recurrence rate of common bile duct stones in the training set was 17.5% (72/412). Multivariate logistic regression analysis showed that stone length, stone number, mixed stones, periampullary diverticulum, postoperative cholecystectomy, nipple incision were risk factors for recurrence of common bile duct stones after ERCP (all P<0.05). Small incision of nipple assisted with large balloon dilatation, incision of nipple titanium splint synthesis, and postoperative ursodeoxycholic acid were protective factors for recurrence of common bile duct stones after ERCP (all P<0.05). The concordance index of the nomogram model based on the above influencing factors was 0.791(95% CI: 0.633-0.892), and the area under the ROC curve for predicting postoperative recurrence of common bile duct stones in the training set and the validation set were 0.905(95% CI: 0.819-0.987) and 0.873(95% CI: 0.809-0.935), respectively. The calibration curve was basically consistent with the ideal curve, and the concordanceindex of internal validation was 0.781(95% CI: 0.628-0.874). Conclusion:The nomogram model based on the influencing factors of common bile duct stone recurrence can predict the risk of common bile duct stone recurrence after ERCP.

Objective:To investigate the differences of comprehensively curative effect of neuro navigation system(NNS)-guided minimally invasive puncture(MIP)and conventional craniotomy hematoma evacuation(CHE)in treatment for traumatic intracerebral hemorrhage,and analyze the mechanisms of affecting the differences of the trajectories postoperative neurologically functional recovery between two kinds of surgical methods.Methods:Based on the design of multicenter prospective cohort study,a total of 240 patients with traumatic intracerebral parenchymal hemorrhage,who admitted to the Neurosurgery Center of Rugao Hospital of Traditional Chinese Medicine between June 2021 and May 2024,were selected.They were randomized into the NNS group(n=120)and the CHE group(n=120)by using a stratified block randomization method.The NNS group underwent NNS-guided surgical intervention,while the CHE group received conventional craniotomy.The primary endpoint was hematoma evacuation rate at the postoperative 7th day.The secondary endpoints encompassed surgical parameters,complications,and the prognostic indicators of function.Microstructural assessment was performed by using three-dimensional image fusion technique[three-dimensional-T1weighted imaging magnetic resonance imaging(3D-T1WI MRI)combined with thin-slice computed tomography(CT)]and tract-based spatial statistics(TBSS).Results:At the dimension of hematoma evacuation,the average hematoma evacuation rate of NNS group was(88.37±6.52)%at the postoperative 7th day,which was significantly higher than(76.15±10.32)%of CHE group,and the residual hematoma volume of NNS group was(5.23±2.15)mL at the postoperative 7th day,which was less than(11.49±4.78)ml,and the differences of them between two groups were significant(t=9.843,7.015,P<0.05),respectively.The surgical trauma parameters appeared polarization:the mean incision length in the NNS group was(3.15±0.73)cm,which reduced 76.3%of(13.24±2.15)cm of the CHE group,with statistically significant difference(Z=15.327,P<0.05).The operative duration of NNS group was(68.34±15.32)min,which was shorter than(142.56±23.48)min,and the difference was significant(t=29.846,P<0.05).The radiation dose of NNS group was(312.45±85.32)cGy·cm2,which was significantly higher than(45.23±12.15)cGy·cm2 of CHE group,and the difference was significant(Z=24.156,P<0.05).The volume of intraoperative blood transfusion of NNS group was(50.34±25.36)ml,which was significantly less than(325.67±158.32)ml,and the difference was significant(Z=18.943,P<0.05),The result of complication genealogy analysis indicated that the re-bleeding incidence of the NNS group was 6.67%,which decreased by 9.16%than 15.83%of the CHE group,and the difference of that between two groups was statistical significance(x2=5.627,P<0.05).However,there was not significant difference in infection rates and incidences of deep vein thrombosis between the two groups(P>0.05).For functional recovery,the proportion of patients whose modified Rankin Scale(mRS)scores was≤2 at the postoperative 90th day was 52.50%in the NNS group,which increased 13.33%than 39.17%in the CHE group,and the difference of that between two groups was statistical significance(x2=4.302,P<0.05).Additionally,the improvement value of National Institutes of Health Stroke Scale(NIHSS)was(9.34±4.156)in the NNS group,which existed marginal advantage of 2.19 points than(7.15±5.327)of the CHE group,and the difference was significant between two groups(Z=3.842,P<0.05).Conclusion:NNS-guided MIP appears notable advantages in enhancing hematoma evacuation efficiency and improving prognosis of neurological function.However,its increased amount of radiation exposure,and risks of specific complication should be considered.The craniotomy approach remains indispensable for complex hematoma morphologies.

Objective:To construct and validate a nomogram prediction model for the recurrence of common bile duct stones after endoscopic retrograde cholangiopancreatography (ERCP) in patients with common bile duct stones.Methods:The clinical data of 515 patients with common bile duct stones treated in Yancheng First People's Hospital from January 2018 to December 2022 were retrospectively analyzed, including 273 males and 242 females, aged (65.5±12.1) years. According to the ratio of 8∶2, all cases were randomly divided into a training set ( n=412) and a validation set ( n=103). According to whether common bile duct stones recurred after ERCP, 412 patients in the training set were divided into two groups: the recurrence group ( n=72) and the non-recurrence group ( n=340). The patients' gender, age, length and diameter of stones, number of stones, diameter of common bile duct and other clinical data were recorded. The logistic regression model was used to analyze the risk factors of recurrence, and a nomogram was constructed based on the analysis results. The concordanceindex, area under the receiver operating characteristic (ROC) curve and calibration chart were used to evaluate the model. Bootstrap self sampling method was used to internally verify the prediction model. Results:The recurrence rate of common bile duct stones in the training set was 17.5% (72/412). Multivariate logistic regression analysis showed that stone length, stone number, mixed stones, periampullary diverticulum, postoperative cholecystectomy, nipple incision were risk factors for recurrence of common bile duct stones after ERCP (all P<0.05). Small incision of nipple assisted with large balloon dilatation, incision of nipple titanium splint synthesis, and postoperative ursodeoxycholic acid were protective factors for recurrence of common bile duct stones after ERCP (all P<0.05). The concordance index of the nomogram model based on the above influencing factors was 0.791(95% CI: 0.633-0.892), and the area under the ROC curve for predicting postoperative recurrence of common bile duct stones in the training set and the validation set were 0.905(95% CI: 0.819-0.987) and 0.873(95% CI: 0.809-0.935), respectively. The calibration curve was basically consistent with the ideal curve, and the concordanceindex of internal validation was 0.781(95% CI: 0.628-0.874). Conclusion:The nomogram model based on the influencing factors of common bile duct stone recurrence can predict the risk of common bile duct stone recurrence after ERCP.

Polygala tenuifolia,commonly known as Yuanzhi(YZ)in Chinese,has been shown to possess anti-insomnia properties.However,the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear.Herein,we investigated the active components and neurochemical mechanism of YZ extracts using liquid chromatography tandem mass spectrometry(LC-MS/MS)-based pharmaco-metabolomics and mass spectrometry imaging(MSI)-based spatial resolved metabolomics.According to the results,17 prototypes out of 101 ingredients in the YZ extract were detected in both the plasma and brain,which might be the major components contributing to the sedative-hypnotic effects.Network pharmacology analysis revealed that these prototypes may exert their effects through neuroactive ligand-receptor interaction,serotonergic synapse,dopaminergic synapse,and dopaminergic synapse,among other pathways.LC-MS/MS-based targeted metabolomics and Western blot(WB)revealed that tryptophan-serotonin-melatonin(Trp-5-HT-Mel)and tyrosine-norepinephrine-adrenaline(Tyr-Ne-Ad)are the key regulated pathways.Dopa decarboxylase(DDC)upregulation and phenylethanolamine N-methyltransferase(PNMT)downregulation further confirmed these pathways.Furthermore,MSI-based spatially resolved metabolomics revealed notable alterations in 5-HT in the pineal gland(PG),and Ad in the brainstem,including the middle brain(MB),pons(PN),and hypothalamus(HY).In summary,this study illustrates the efficacy of an integrated multidimensional metabolomics approach in unraveling the sedative-hypnotic effects and neurochemical mechanisms of a Chinese herbal medicine,YZ.

Objective To explore the effect and possible mechanism of berberine on the macro-phage polarization of human myeloid leukemia monocytic cell line THP-1 induced by oxidized low-density lipoprotein(ox-LDL).Methods THP-1 cells were induced into macrophages by PMA,and then according to different concentrations of berberine,the cells were divided into con-trol group,and 5,10,20,40 and 50 μmol/L berberine groups.After intervention for 24 or 48 h,CCK8 assay was used to detect cell viability for optimal concentration and time of berberine treat-ment.PMA-induced THP-1 macrophages were assigned into blank group,model group(ox-LDL),berberine group,inhibitor group(phosphatidyl inositol 3-kinase(PI3K)inhibitor LY294002)and berberine+inhibitor group(berberine+LY294002).The contents of inducible nitric oxide syn-thase(iNOS)and TGF-β1 were detected by ELISA.qPCR was employed to measure the mRNA expression of TNF-α,arginase 1(Arg1),PI3K and protein kinase B Akt1,and Western blotting was applied to detect the protein levels of Akt1 and phosphorylated protein kinase B antibody(p-Akt1).Results In 24 h after intervention,the macrophage activity was significantly lower in the 40 and 50 μmol/L berberine groups than the control group(P＜0.05),and after 48 h,the ac-tivity in all the 5 doses of berberine groups was obviously lower than that in the control group[(0.89±0.02)％,(0.82±0.03)％,(0.71±0.02)％,(0.62±0.03)％and(0.53±0.02)％vs(1.01±0.01)％,P＜0.05].Berberine treatment of 20 μmol/L for 24 h had little effect on cell viability,and the dose and the time were regarded as the best concentration and time.Compared with the blank group,iNOS content and TNF-α mRNA level were increased in the model group,while TGF-β1 content,mRNA levels of Arg1,PI3K and Akt1,and p-Akt1/Akt1 protein levels were de-creased(P＜0.05).iNOS content and TNF-α mRNA level were decreased,while TGF-β1 content,mRNA levels of Arg1,PI3K and Akt1 and protein levels of p-Akt1/Akt1s were increased in the berberine group than the model group(P＜0.05).Compared with the berberine group,iNOS con-tent and TNF-α mRNA level were increased,while mRNA levels of Arg1,PI3K and Akt1 and protein levels of p-Akt1/Akt1 were decreased in the berberine+inhibitor group(P＜0.05).Con-clusion Berberine can inhibit the inflammatory response of THP-1 macrophages induced by ox-LDL by activating PI3K/Akt1 pathway,and inhibit the M1 polarization and promote the M2 polarization of macrophages.

Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.
Animals ; Haplorhini ; Axons ; Motor Neurons ; Interneurons ; Macaca ; Dependovirus/genetics* ; Genetic Vectors

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

By consulting the ancient and moderm literature， this paper makes a textual research on the name， origin， quality evaluation， harvesting and processing of Olibanum， so as to provide a basis for the development of the famous classical formulas containing this medicinal material. According to the herbal textual research， the results showed that Olibanum was first described as a medicinal material by the name of Xunluxiang in Mingyi Bielu（《名医别录》）， until Ruxiang had been used as the correct name since Bencao Shiyi（《本草拾遗》） in Tang dynasty. The main origin was Boswellia carterii from Burseraceae family. The mainly producing areas in ancient description were ancient India and Arabia， while the modern producing areas are Somalia， Ethiopia and the southern Arabian Peninsula. The medicinal part of Olibanum in ancient and modern times is the resin exuded from the bark， which has been mainly harvested in spring and summer. It is concluded that the better Olibanum has light yellow， granular， translucent， no impurities such as sand and bark， sticky powder and aromatic smell. There were many processing methods in ancient times， including cleansing（water flying， removing impurities）， grinding（wine grinding， rush grinding）， frying（stir-frying， rush frying， wine frying）， degreasing， vinegar processing， decoction. In modern times， the main processing methods are simplified to cleansing， stir-frying and vinegar processing. Nowadays， the commonly used specifications include raw， fried and vinegar-processed products. Among the three specifications， raw products is the Olibanum after cleansing， fried products is a kind of Olibanum processed by frying method， vinegar-processed products is the processed products of pure frankincense mixed with vinegar. Based on the research results， it is recommended to select the resin exuded from the bark of B. carterii for the famous classical formulas such as Juanbitang containing Olibanum， processing method should be carried out in accordance with the processing requirements of the formulas， otherwise used the raw products if the formulas without clear processing requirements.