This study was aimed at exploring the mechanism underlying the effects of nitidine chloride against Talaromyces marnef-fei through network pharmacology analysis.We collected NC and TM action targets from various databases;constructed a protein-protein interaction(PPI)network by using common drug and disease targets;and performed KEGG pathway and GO enrichment analy-ses.In vitro cellular experiments were conducted to test the antibacterial ability of NC at various concentrations,qPCR was used to de-tect the mRNA expression of genes in the target pathway,and WB was used to examine the expression of proteins associated with tar-get signaling pathways in cells.We identified 153 target genes for NC and 2 095 target genes for TM,among which 23 targets over-lapped.By integrating the PPI network with KEGG enrichment analysis,we selected key target genes in the MAPK signaling pathway,such as FLT1,FLT3,CD38,and PRF1.The CFU results indicated that NC had favorable antibacterial capability.Moreover,qPCR demonstrated that NC downregulated the mRNA expression of FLT1,FLT3,and RPS6KA3,and upregulated the mRNA expression of MAP3K8.WB findings indicated that NC downregulated the expression of RSK2,VEGF,and FLT3 proteins,and upregulated the ex-pression of MAP3K8 protein.NC may exert its anti-TM effects by downregulating the expression of RSK2,VEGF,and FLT3 proteins,thereby inhibiting MAPK pathway activation.The potential targets and signaling pathways underlying NC's anti-TM action may pro-vide new insights to guide the clinical application of NC.

OBJECTIVE To investigate the effect of hyperoside on high glucose-induced excessive proliferation of retinal endo-thelial cells(RECs)and its possible mechanism.METHODS Diabetic retinopathy(DR)models were established in male Sprague-Dawley(SD)rats.DR rats were treated with low-and high-dose hyperoside(DR+L-HY group and DR+H-HY group).Additional-ly,the normal control(NC)group,DR non-intervention(DR)group and DR+calcium dobesilate intervention(DR+CD)group were set up.The differences in the number of RECs in retinal blood vessels were observed and compared among all groups after intervention.In addition,RECs were inoculated into cell culture plates after normal culture and subculture.They were divided into 5 groups according to different treatments:normal glucose(NG)group,high glucose(HG)group,mannitol(MT)group,high glucose+low concentration of hyperoside(HG+H100)group and high glucose+high concentration of hyperoside(HG+H400)group.The activ-ity,cell migration and tubule formation of RECs in each group were detected and compared by CCK-8,cell migration and tubule for-mation assays.Western blot and qPCR were used to detect the expression of NADPH Oxidase 4(NOX4)and thioredoxin interacting protein(TXNIP)in each group.RESULTS The number of RECs in the DR group was significantly increased compared to the NC group(P<0.01).In contrast,the DR+L-HY,DR+H-HY,and DR+CD groups all showed significant decreases in RECs number compared to the DR group(P<0.05,P<0.01),and the reduction of RECs in the DR+H-HY group was significantly greater than that in the DR+L-HY group(P<0.05).Furthermore,the cell activity,migration number and tube formation number of RECs in the HG group were significantly higher than those in the NG group(P<0.05,P<0.01).The protein and mRNA expression levels of NOX4 and TXNIP in the HG group were also significantly higher than those in the NG group(P<0.01).However,the RECs activity,RECs mi-gration number and tube formation number in the HG+H100 group and the HG+H400 group were significantly lower than those in the HG group(P<0.05,P<0.01).The expression levels of NOX4 and TXNIP in both groups were significantly lower than those in the HG group(P<0.05,P<0.01),and the RECs activity,migration number,tube formation number,and the expression of NOX4 and TXNIP in the HG+H400 group were further significantly decreased compared with those in the HG+H100 group(P<0.01).CONCLU-SION Hyperoside could significantly inhibit the high glucose-induced excessive proliferation of RECs.The mechanism may be relat-ed to the inhibition of NOX4/TXNIP activation in high-glucose environment.

Reach-to-grasp movements require integrating information on both object location and grip type, but how these elements are planned and to what extent they interact remains unclear. We designed a new experimental paradigm in which monkeys sequentially received reach and grasp cues with delays, requiring them to retain and integrate both cues to grasp the goal object with appropriate hand gestures. Neural activity in the dorsal premotor cortex (PMd) revealed that reach and grasp were similarly represented yet not independent. Upon receiving the second cue, the PMd continued encoding the first, but over half of the neurons displayed incongruent modulations: enhanced, attenuated, or even reversed. Population-level analysis showed significant changes in encoding structure, forming distinct neural patterns. Leveraging canonical correlation analysis, we identified a shared subspace preserving the initial cue's encoding, contributed by both congruent and incongruent neurons. Together, these findings reveal a novel perspective on the interactive planning of reach and grasp within the PMd, providing insights into potential applications for brain-machine interfaces.
Animals ; Motor Cortex/physiology* ; Hand Strength/physiology* ; Macaca mulatta ; Psychomotor Performance/physiology* ; Neurons/physiology* ; Male ; Cues ; Movement/physiology* ; Gestures

This study was aimed at exploring the mechanism underlying the effects of nitidine chloride against Talaromyces marnef-fei through network pharmacology analysis.We collected NC and TM action targets from various databases;constructed a protein-protein interaction(PPI)network by using common drug and disease targets;and performed KEGG pathway and GO enrichment analy-ses.In vitro cellular experiments were conducted to test the antibacterial ability of NC at various concentrations,qPCR was used to de-tect the mRNA expression of genes in the target pathway,and WB was used to examine the expression of proteins associated with tar-get signaling pathways in cells.We identified 153 target genes for NC and 2 095 target genes for TM,among which 23 targets over-lapped.By integrating the PPI network with KEGG enrichment analysis,we selected key target genes in the MAPK signaling pathway,such as FLT1,FLT3,CD38,and PRF1.The CFU results indicated that NC had favorable antibacterial capability.Moreover,qPCR demonstrated that NC downregulated the mRNA expression of FLT1,FLT3,and RPS6KA3,and upregulated the mRNA expression of MAP3K8.WB findings indicated that NC downregulated the expression of RSK2,VEGF,and FLT3 proteins,and upregulated the ex-pression of MAP3K8 protein.NC may exert its anti-TM effects by downregulating the expression of RSK2,VEGF,and FLT3 proteins,thereby inhibiting MAPK pathway activation.The potential targets and signaling pathways underlying NC's anti-TM action may pro-vide new insights to guide the clinical application of NC.

OBJECTIVE To investigate the effect of hyperoside on high glucose-induced excessive proliferation of retinal endo-thelial cells(RECs)and its possible mechanism.METHODS Diabetic retinopathy(DR)models were established in male Sprague-Dawley(SD)rats.DR rats were treated with low-and high-dose hyperoside(DR+L-HY group and DR+H-HY group).Additional-ly,the normal control(NC)group,DR non-intervention(DR)group and DR+calcium dobesilate intervention(DR+CD)group were set up.The differences in the number of RECs in retinal blood vessels were observed and compared among all groups after intervention.In addition,RECs were inoculated into cell culture plates after normal culture and subculture.They were divided into 5 groups according to different treatments:normal glucose(NG)group,high glucose(HG)group,mannitol(MT)group,high glucose+low concentration of hyperoside(HG+H100)group and high glucose+high concentration of hyperoside(HG+H400)group.The activ-ity,cell migration and tubule formation of RECs in each group were detected and compared by CCK-8,cell migration and tubule for-mation assays.Western blot and qPCR were used to detect the expression of NADPH Oxidase 4(NOX4)and thioredoxin interacting protein(TXNIP)in each group.RESULTS The number of RECs in the DR group was significantly increased compared to the NC group(P<0.01).In contrast,the DR+L-HY,DR+H-HY,and DR+CD groups all showed significant decreases in RECs number compared to the DR group(P<0.05,P<0.01),and the reduction of RECs in the DR+H-HY group was significantly greater than that in the DR+L-HY group(P<0.05).Furthermore,the cell activity,migration number and tube formation number of RECs in the HG group were significantly higher than those in the NG group(P<0.05,P<0.01).The protein and mRNA expression levels of NOX4 and TXNIP in the HG group were also significantly higher than those in the NG group(P<0.01).However,the RECs activity,RECs mi-gration number and tube formation number in the HG+H100 group and the HG+H400 group were significantly lower than those in the HG group(P<0.05,P<0.01).The expression levels of NOX4 and TXNIP in both groups were significantly lower than those in the HG group(P<0.05,P<0.01),and the RECs activity,migration number,tube formation number,and the expression of NOX4 and TXNIP in the HG+H400 group were further significantly decreased compared with those in the HG+H100 group(P<0.01).CONCLU-SION Hyperoside could significantly inhibit the high glucose-induced excessive proliferation of RECs.The mechanism may be relat-ed to the inhibition of NOX4/TXNIP activation in high-glucose environment.

Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.

Objective:To evaluate the effectiveness of left ventricular assist device (LVAD)implantation via minimally invasive thoracotomy.Methods:From April 2022 to October 2023, we retrospectively collected and analyzed the perioperative data of 16 patients underwent LVAD via minimally invasive thoracotomy in our institute. 16 patients included 10 males and 6 females, the mean age was(58.6±7.6)(49-76)years old, BSA was (1.75±0.90)(1.35-2.01)m 2, 6 cases of dilated cardiomyopathy (DCM), 8 cases of ischemic cardiomyopathy (ICM) and 2 cases of end-stage valvular heart disease. LVAD type included 8 cases of CH-VAD, 7 cases of HeartCon and 1 case of Corheart-6. All the 16 patients underwent LVAD implantation were performed in condition of CPB, 13 patients on-beating heart, 3 patients with heart arrest. The outflow graft of 15 patients were place at ascending aorta, 1 patient was descending aorta. Results:The average surgical time was about 5.09 h, CPB time was(137±32)min, and the mechanical ventilation time was (20.8±13.6)h, stay in the ICU was(10.0±6.3)days, and the length of stay was(45.4±17.0)days. No case transition to sternotomy, no case in right ventricular failure, and no death case during 30 days.Conclusion:Minimally invasive thoracotomy approach is a safe and reliable method for left ventricular assist devices implantation, and can be used as a choice for LVAD implantation.

Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.

Objective　To explore the effect of Mp1p on host macrophages through transcriptomics combined with metabolomics. Methods Firstly, a THP-1 macrophage strain (THP-1-Mp1p+) stably expressing Mp1p was constructed using lentivirus. Secondly, using high-throughput RNA sequencing (RNA Seq) technology, the expression level of intracellular mRNA was detected in transcriptomics analysis to determine differentially expressed genes; In metabolomics analysis, metabolite identification was performed through database comparison, and pathway analysis was performed on differential metabolites to reveal potential mechanisms of action. Finally, the results of metabolomics and transcriptomics were combined for analysis, and differential metabolites and genes were analyzed to further elucidate the mechanism of action of Mp1p on macrophages. Results Transcriptome analysis showed that, compared with the negative control group, the THP-1-Mp1p+ group had a total of 1 180 differentially expressed genes (DEGs), with 345 upregulated genes and 835 downregulated genes. GO enrichment analysis of DEGs showed that there were 135 differentially expressed genes, including 105 in biological processes (BP), 28 in cellular components (CC), and 2 in molecular functions (MF). The KEGG analysis results showed that the effect of Mp1p on THP-1 macrophages was highly correlated with the TNF pathway. The metabolomic analysis found that both the blank control group and the THP-1-Mp1p+ macrophage group achieved good separation between QC samples in both positive and negative ion modes. The threshold for significant differential metabolites was set at: VIP≥1 and T-test P<0.05, resulting in the identification of 488 differential metabolites, with 230 in the positive ion mode and 258 in the negative ion mode. Pathway enrichment analysis of the identified metabolites pointed to significant enrichment in metabolic pathways. The combined analysis confirmed that the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and NF-kappaB signaling pathway were important metabolic pathways involved. Conclusions The virulence factor Mp1p may affect host macrophages by modulating the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and NF-kappaB signaling pathway. The findings contribute to a better understanding of the mechanisms of action of Mp1p and may offer potential directions for the selection of relevant diagnostic and therapeutic targets in the future.

Objective:To explore the technical points and efficacy of gradual traction-unlocking closed reduction technique (GT-UCRT) for Tile C old pelvic fractures.Methods:From August 2012 to June 2021, 6 patients with Tile C old pelvic fracture were treated and followed up at Department of Orthopedics, The Fourth Medical Center, General Hospital of Chinese PLA. They were 4 males and 2 females with an age of (35.8±10.5) years. By Tile classification: 4 cases of type C1.2, 1 case of type C1.3, and 1 case of type C2; time from injury to surgery: 153.8 (64.3, 204.8) days. The 6 patients were treated with GT-UCRT. The time for gradual traction reduction, operation time, hospital stay, intraoperative blood loss and complications were recorded. The modified Matta score was used to evaluate the reduction quality of pelvic fractures, and the Majeed score was used to evaluate the pelvic function at the last follow-up.Results:The 6 patients were followed up for (40.3±22.9) months (from 12 to 72 months) after surgery. The time for gradual traction reduction was (26.7±4.6) days, operation time (119.2±4.6) minutes, hospital stay (11.5±2.9) days, and intraoperative blood loss (533.3±189.6) mL. By the modified Matta score, the pelvic reduction after surgery was rated as satisfactory in 5 cases and as unsatisfactory in 1 case. The length disparity between both lower limbs in the 6 patients was (6.9±1.6) cm before surgery and (1.0±0.4) cm immediately after surgery, showing a statistically significant difference ( t=11.135, P<0.001). One fracture healed 3 months after surgery and 5 fractures 6 months after surgery. The Majeed pelvic score at the last follow-up was (80.8±9.0) points for the 6 patients, yielding 2 excellent cases, 3 good cases and 1 fair case. Delayed wound healing was reported in 1 patient, calf intermuscular venous thrombosis in 2 cases, and emotional anxiety and sleep disorder in 1 patient. No new lumbosacral plexus injury was found in any patient. Conclusions:In the treatment of Tile C old pelvic fractures, since our self-designed GT-UCRT combines the advantages of Ilizarov technique and unlocking closed reduction technique, it can not only protect the lumbosacral plexus but also obtain satisfactory reduction of the fracture.