ObjectiveTo investigate the effects of mitotically-associated long non-coding RNA （lncRNA MANCR） on the proliferation，migration， and epithelial mesenchymal transition （EMT） of gastric cancer （GC） cells by regulating the microRNA-50-5p （miR-150-5p）/non-metastatic melanoprotein B （GPNMB） axis. MethodsThe mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in 42 cases of GC tissue and adjacent tissue resected during surgery in the First Hospital of Hebei Medical University from June 2022 to September 2023 were detected by Real-time PCR. Human gastric mucosal epithelial cells GES-1 and human GC cells BGC-823 were cultured in vitro， and their lncRNA MANCR expression was detected. BGC-823 cells were randomly separated into control group （routine culture），sh-NC group （with sh-NC transfected），sh-MANCR group （with sh-MANCR transfected），sh-MANCR + anti-NC group （with sh-MANCR and anti-NC both transfected），and sh-MANCR + anti-miR-150-5p group （with sh-MANCR and anti-miR-150-5p both transfected）. The mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in the BGC-823 cells of all groups were analyzed. EdU staining was used to detect the proliferation of BGC-823 cells. Transwell assay was used to detect the migration and invasion of BGC-823 cells. The expressions of EMT-related proteins E-cadherin，N-cadherin，Vimentin， and GPNMB were detected by Western blot. The interactions between lncRNA MANCR and miR-150-5p and between miR-150-5p and GPNMB were analyzed by dual luciferase reporter assay. ResultsThe mRNA expressions of lncRNA MANCR and GPNMB in GC tissue were higher than those in adjacent tissue，and the expression of miR-150-5p was lower than that in adjacent tissue （P<0.05）. Compared with that in GES-1，lncRNA MANCR expression in BGC-823 cells was increased （P<0.05）. Compared with those in the sh-NC group and control group，the EdU-positive cell rate，migration number，invasion number，the mRNA expressions of lncRNA MANCR and GPNMB， and the expressions of protein，N-cadherin protein， and Vimentin protein in the BGC-823 cells in the sh-MANCR group were lower ，and the protein expressions of miR-150-5p and E-cadherin were higher （P<0.05）. Compared with those in the sh-MANCR group and the sh-MANCR + anti-NC group，the protein expressions of miR-150-5p and E-cadherin in the sh-MANCR + anti-miR-150-5p group were decreased. The EdU-positive cell rate，migration number，invasion number，mRNA expressions of GPNMB， and expressions of protein，N-cadherin protein， and Vimentin protein were increased （P<0.05）. lncRNA MANCR could target the negative regulation of miR-150-5p，and miR-150-5p could target the negative regulation of GPNMB. ConclusionKnockout of lncRNA MANCR can inhibit the proliferation，migration， and EMT of GC cells by regulating the miR-150-5p/GPNMB axis.

ObjectiveTo investigate the effects of mitotically-associated long non-coding RNA （lncRNA MANCR） on the proliferation，migration， and epithelial mesenchymal transition （EMT） of gastric cancer （GC） cells by regulating the microRNA-50-5p （miR-150-5p）/non-metastatic melanoprotein B （GPNMB） axis. MethodsThe mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in 42 cases of GC tissue and adjacent tissue resected during surgery in the First Hospital of Hebei Medical University from June 2022 to September 2023 were detected by Real-time PCR. Human gastric mucosal epithelial cells GES-1 and human GC cells BGC-823 were cultured in vitro， and their lncRNA MANCR expression was detected. BGC-823 cells were randomly separated into control group （routine culture），sh-NC group （with sh-NC transfected），sh-MANCR group （with sh-MANCR transfected），sh-MANCR + anti-NC group （with sh-MANCR and anti-NC both transfected），and sh-MANCR + anti-miR-150-5p group （with sh-MANCR and anti-miR-150-5p both transfected）. The mRNA expressions of lncRNA MANCR，miR-150-5p， and GPNMB in the BGC-823 cells of all groups were analyzed. EdU staining was used to detect the proliferation of BGC-823 cells. Transwell assay was used to detect the migration and invasion of BGC-823 cells. The expressions of EMT-related proteins E-cadherin，N-cadherin，Vimentin， and GPNMB were detected by Western blot. The interactions between lncRNA MANCR and miR-150-5p and between miR-150-5p and GPNMB were analyzed by dual luciferase reporter assay. ResultsThe mRNA expressions of lncRNA MANCR and GPNMB in GC tissue were higher than those in adjacent tissue，and the expression of miR-150-5p was lower than that in adjacent tissue （P<0.05）. Compared with that in GES-1，lncRNA MANCR expression in BGC-823 cells was increased （P<0.05）. Compared with those in the sh-NC group and control group，the EdU-positive cell rate，migration number，invasion number，the mRNA expressions of lncRNA MANCR and GPNMB， and the expressions of protein，N-cadherin protein， and Vimentin protein in the BGC-823 cells in the sh-MANCR group were lower ，and the protein expressions of miR-150-5p and E-cadherin were higher （P<0.05）. Compared with those in the sh-MANCR group and the sh-MANCR + anti-NC group，the protein expressions of miR-150-5p and E-cadherin in the sh-MANCR + anti-miR-150-5p group were decreased. The EdU-positive cell rate，migration number，invasion number，mRNA expressions of GPNMB， and expressions of protein，N-cadherin protein， and Vimentin protein were increased （P<0.05）. lncRNA MANCR could target the negative regulation of miR-150-5p，and miR-150-5p could target the negative regulation of GPNMB. ConclusionKnockout of lncRNA MANCR can inhibit the proliferation，migration， and EMT of GC cells by regulating the miR-150-5p/GPNMB axis.

Objective:To study the clinical outcome of palmar approach to on-top plasty in the treatment of unequal radial polydactyly.Methods:A retrospective analysis was conducted on patients with unequal radial polydactyly in which neither thumb duplicates possess both well-developed proximal and distal components. All the patients underwent palmar approach to on-top plasty between September 2013 and September 2023 at Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine and Shanxi Children’s Hospital. At the final follow-up, the active flexion-extension range of motion of the first metacarpophalangeal and interphalangeal joints was measured, along with grip and pinch strength. The Vancouver scar scale was used to assess scar formation (total score 0-15, with higher scores indicating more severe scarring). Additionally, the pediatric quality of life inventory (total score 0-100, with higher scores indicating better quality of life, evaluated by the children themselves or by their parents/guardians on their behalf) and the satisfaction questionnaire (total score ranges from 1 to 5, with higher scores indicating greater satisfaction) were used to assess the patients’ daily quality of life and parents’satisfaction.Results:A total of 28 pediatric patients were included, comprising 15 males and 13 females, with an average age of 15 months (range: 10-36 months). All cases presented unilateral radial polydactyly, including 18 right hands and 10 left hands. The mean follow-up duration was 4.2 years (range: 1.5-6.0 years). All incisions healed in one stage, and the skin flaps survived well without infection. Joint stability was maintained without any deviation. All reconstructed thumbs demonstrated satisfactory aesthetic appearance. The reconstructed thumbs demonstrated mean active flexion-extension arcs of 76° (range 61°-85°) at the first metacarpophalangeal joint, and 42° (range 21°-65°) at the interphalangeal joint. The grip strength of the hand was 82% (63%-90%) of the normal opposite hand. The key, tip and tripod pinch strength were 76%(66%-83%), 77%(66%-85%) and 79%(68%-87%) of the normal opposite hand, respectively. No scar hyperplasia was found in all cases, and the Vancouver scar scale score was 1.2(0-3) points. The self-assessment score of the children on the pediatric quality of life inventory was 86 points, and the score of the parents/guardians was 91 points. In terms of family satisfaction, 23 patients scored 5, and 5 patients scored 4.Conclusion:The use of palmar approach to on-top plasty to treat unequal radial polydactyly can achieve functional and aesthetic results.

Objective: To investigate the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF) on histone H3 lysine 18 lactylation (H3K18la) in the hippocampus of rats with diabetes mellitus complicated with depression (DD) and predict the regulatory genes of H3K18la. Methods: Male Sprague-Dawley rats were divided into control, model, and positive drug (metformin [0.18 g/kg] and fluoxetine [1.8 mg/kg]) groups, and the three groups were treated with high, medium, and low ZGJTJYF doses (20.52, 10.26, and 5.13 g/kg, respectively), with 10 rats per group. After treatment, the forced swimming and water maze tests were performed to assess depressive-like behaviors and cognitive function. An enzyme-linked immunosorbent assay was used to measure blood insulin, glycosylated hemoglobin, lactate levels, and lactate content in the hippocampus. Western blotting was used to detect H3K18la expression in the hippocampus. Cleavage Under Targets and lagmentation(CUT&Tag) experiments targeted hippocampal H3K18la epigenetic modification regions to analyze the transcription factors bound by H3K18la. Kyoto Encyclopedia of Genes and Genomes and Protein-Protein Interaction networks were constructed to identify key pathways and target genes regulated by H3K18la. Results: Compared with the normal group, the model group rats showed prolonged immobility time in the forced swim test, increased escape latency in the water maze experiment, decreased target quadrant distance ratio (P<0.01), increased serum lactate content, and decreased lactate content in hippocampal homogenate (P<0.01), as well as decreased H3K18la protein expression in the hippocampus (P<0.01). Compared with the model group, ZGJTJYF reduced the immobility time in the forced swim test and the escape latency in the water maze test (P<0.01), while the distance ratio in the target quadrant increased (P<0.01) in model rats. Lowered fasting blood glucose, insulin, and glycosylated hemoglobin levels (P<0.05, P<0.01) were also observed. ZGJTJYF also increased the lactate content and H3K18la protein expression in hippocampal homogenate (P<0.05, P<0.01). The DNA sequences bound by H3K18la were predominantly enriched at the transcription start sites. ZGJTJYF modulated H3K18la-associated pathways, including cell adhesion junctions, tumor growth factor-beta (TGF-β) signaling, stem cell pluripotency regulation, mitogen-activated protein kinase(MAPK) signaling pathway, and insulin resistance, leading to the identification of 12 target genes. Conclusion ZGJTJYF enhances hippocampal lactate levels and H3K18la modification in DD rats, which may regulate neural cell interactions, neurogenic stem cell function, TGF-β signaling, MAPK signaling, and insulin resistance pathways.

Objective To identify clinicopathological parameters that differentiate between very high-risk and ordinary high-risk gas-trointestinal stromal tumors(GISTs)to provide guidance for clinical treatment and follow-up monitoring.Methods A retrospective cohort study was conducted,collecting 174 cases of high-risk GISTs initially diagnosed and surgically resected at Tianjin Medical University Cancer Institute and Hospital between January 1st,2011,and December 31st,2019.Based on long-term follow-up data,the X-tile software was used to identify key parameters for screening very high-risk GISTs from ordinary high-risk GISTs,and the results were validated by using high-risk GIST cases from the cBioPortal database.Results Among the 174 high-risk GIST cases,the X-tile software indicat-ed that the maximum tumor diameter of 14 cm,the mitotic count of 14/5 mm2,and the Ki-67 proliferation index of 10%were the optimal cutoff values for distinguishing very high-risk GISTs from ordinary high-risk GISTs.Univariate survival analysis confirmed that these cutoff values were associated with progression free survival(PFS,all P<0.05).Multivariate survival analysis confirmed that the maximum tumor diameter≥14 cm(HR=5.727,P<0.01),mitotic count≥14/5 mm2(HR=2.454,P=0.047),and Ki-67 proliferation index≥10%(HR=2.275,P=0.047)were independent risk factors for tumor progression in high-risk GIST patients.High-risk GISTs with any one of the three parameters more than or equal to its optimal cutoff value were defined as very high-risk GISTs,and the other GISTs were defined as ordinary high-risk GISTs.Compared to very high-risk GIST patients,the ordinary high-risk GIST patients had superior PFS(P<0.01),and a trend toward better overall survival(OS,P=0.082).Stratified analysis showed that,in subgroups of patients with gastric or non-gas-tric primary tumors,those receiving or not receiving adjuvant therapy,and those with KIT proto-oncogene,receptor tyrosine kinase(KIT)gene mutations,ordinary high-risk GIST patients all exhibited superior PFS compared to very high-risk GIST patients(all P<0.05).Both PFS and OS of ordinary high-risk GIST patients in the cBioPortal database were better than those of very high-risk GIST patients(both P=0.001).Stratified analysis of the cBioPortal database data showed that,in subgroups of patients with gastric or non-gastric primary tu-mors,those who received adjuvant therapy,and those with KIT gene mutations,ordinary high-risk GIST patients all exhibited superior PFS compared to very high-risk GIST patients(all P<0.05);conversely,among patients who did not receive adjuvant therapy,very high-risk GIST patients showed a trend toward poorer PFS(P=0.366).Conclusions This study has established a method utilizing commonly used clinical parameters to distinguish very high-risk GISTs in clinical practice.However,further validation through multicenter studies with larger sample sizes is still required.

Objective:To investigate the effects of circular RNA fascin actin-bundling protein 1(circFSCN1)on the malignant biological behaviors of gastric cancer cells by regulating the microRNA-429(miR-429)/glycoprotein nonmetastatic melanoma protein B(GPNMB)axis and its mechanisms.Methods:The gastric cancer tissues and corresponding para-cancerous tissues of 54 patients who underwent surgical resection at the First Hospital of Hebei Medical University between September 2022 and September 2023 were collected.The expressions of circFSCN1,miR-429 and GPNMB mRNA in gastric cancer tissues were detected by qPCR.Gastric cancer MGC803 cells were routinely cultured and divided into the control group,the sh-NC group,the sh-circFSCN1 group,the sh-circFSCN1+anti-NC group,and the sh-circFSCN1+anti-miR-429 group.The expressions of circFSCN1,miR-429 and GPNMB mRNA in MGC803 cells of each group were detected by qPCR.The proliferation,migration,invasion and apoptosis of MGC803 cells in each group were detected by CCK-8 method,colony formation assay,Transwell assay and flow cytometry,respectively.Immunofluorescence was used to detect the expressions of GPNMB protein in cells of each group.WB assay was used to detect the expressions of PCNA,MMP-2,GPNMB and Cleaved Caspase-3 proteins in MGC803 cells of each group.Dual luciferase reporter assay and RNA-binding protein immunoprecipitation(RIP)assay were used to verify the binding regulatory relationship between circFSCN1 and miR-429,and between miR-429 and GPNMB.Results:circFSCN1 and GPNMB mRNA were both highly expressed in gastric cancer tissues(both P<0.05),while miR-429 was lowly expressed(P<0.05).Knockdown of circFSCN1 could promote the expression of miR-429 and inhibit the expression of GPNMB mRNA.Inhibition of miR-429 could promote the expression of GPNMB mRNA.Knockdown of circFSCN1 could significantly inhibit the proliferation,migration and invasion abilities of MGC803 cells and promote their apoptosis.Inhibition of miR-429 could partially reverse the effect of circFSCN1 knockdown.Knockdown of circFSCN1 could inhibit the expressions of PCNA,MMP-2 and GPNMB proteins in MGC803 cells and inhibit the expression of cleaved caspase-3 protein.There was a targeted binding and negative regulatory relationship between circFSCN1 and miR-429 and between miR-429 and GPNMB mRNA.Conclusion:Knocking down circFSCN1 inhibits the malignant biological behaviors of gastric cancer cells through the miR-429/GPNMB axis,indicating that circFSCN1 is a potential therapeutic target for gastric cancer.

Objective:To study the clinical outcome of palmar approach to on-top plasty in the treatment of unequal radial polydactyly.Methods:A retrospective analysis was conducted on patients with unequal radial polydactyly in which neither thumb duplicates possess both well-developed proximal and distal components. All the patients underwent palmar approach to on-top plasty between September 2013 and September 2023 at Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine and Shanxi Children’s Hospital. At the final follow-up, the active flexion-extension range of motion of the first metacarpophalangeal and interphalangeal joints was measured, along with grip and pinch strength. The Vancouver scar scale was used to assess scar formation (total score 0-15, with higher scores indicating more severe scarring). Additionally, the pediatric quality of life inventory (total score 0-100, with higher scores indicating better quality of life, evaluated by the children themselves or by their parents/guardians on their behalf) and the satisfaction questionnaire (total score ranges from 1 to 5, with higher scores indicating greater satisfaction) were used to assess the patients’ daily quality of life and parents’satisfaction.Results:A total of 28 pediatric patients were included, comprising 15 males and 13 females, with an average age of 15 months (range: 10-36 months). All cases presented unilateral radial polydactyly, including 18 right hands and 10 left hands. The mean follow-up duration was 4.2 years (range: 1.5-6.0 years). All incisions healed in one stage, and the skin flaps survived well without infection. Joint stability was maintained without any deviation. All reconstructed thumbs demonstrated satisfactory aesthetic appearance. The reconstructed thumbs demonstrated mean active flexion-extension arcs of 76° (range 61°-85°) at the first metacarpophalangeal joint, and 42° (range 21°-65°) at the interphalangeal joint. The grip strength of the hand was 82% (63%-90%) of the normal opposite hand. The key, tip and tripod pinch strength were 76%(66%-83%), 77%(66%-85%) and 79%(68%-87%) of the normal opposite hand, respectively. No scar hyperplasia was found in all cases, and the Vancouver scar scale score was 1.2(0-3) points. The self-assessment score of the children on the pediatric quality of life inventory was 86 points, and the score of the parents/guardians was 91 points. In terms of family satisfaction, 23 patients scored 5, and 5 patients scored 4.Conclusion:The use of palmar approach to on-top plasty to treat unequal radial polydactyly can achieve functional and aesthetic results.

Objective To identify clinicopathological parameters that differentiate between very high-risk and ordinary high-risk gas-trointestinal stromal tumors(GISTs)to provide guidance for clinical treatment and follow-up monitoring.Methods A retrospective cohort study was conducted,collecting 174 cases of high-risk GISTs initially diagnosed and surgically resected at Tianjin Medical University Cancer Institute and Hospital between January 1st,2011,and December 31st,2019.Based on long-term follow-up data,the X-tile software was used to identify key parameters for screening very high-risk GISTs from ordinary high-risk GISTs,and the results were validated by using high-risk GIST cases from the cBioPortal database.Results Among the 174 high-risk GIST cases,the X-tile software indicat-ed that the maximum tumor diameter of 14 cm,the mitotic count of 14/5 mm2,and the Ki-67 proliferation index of 10%were the optimal cutoff values for distinguishing very high-risk GISTs from ordinary high-risk GISTs.Univariate survival analysis confirmed that these cutoff values were associated with progression free survival(PFS,all P<0.05).Multivariate survival analysis confirmed that the maximum tumor diameter≥14 cm(HR=5.727,P<0.01),mitotic count≥14/5 mm2(HR=2.454,P=0.047),and Ki-67 proliferation index≥10%(HR=2.275,P=0.047)were independent risk factors for tumor progression in high-risk GIST patients.High-risk GISTs with any one of the three parameters more than or equal to its optimal cutoff value were defined as very high-risk GISTs,and the other GISTs were defined as ordinary high-risk GISTs.Compared to very high-risk GIST patients,the ordinary high-risk GIST patients had superior PFS(P<0.01),and a trend toward better overall survival(OS,P=0.082).Stratified analysis showed that,in subgroups of patients with gastric or non-gas-tric primary tumors,those receiving or not receiving adjuvant therapy,and those with KIT proto-oncogene,receptor tyrosine kinase(KIT)gene mutations,ordinary high-risk GIST patients all exhibited superior PFS compared to very high-risk GIST patients(all P<0.05).Both PFS and OS of ordinary high-risk GIST patients in the cBioPortal database were better than those of very high-risk GIST patients(both P=0.001).Stratified analysis of the cBioPortal database data showed that,in subgroups of patients with gastric or non-gastric primary tu-mors,those who received adjuvant therapy,and those with KIT gene mutations,ordinary high-risk GIST patients all exhibited superior PFS compared to very high-risk GIST patients(all P<0.05);conversely,among patients who did not receive adjuvant therapy,very high-risk GIST patients showed a trend toward poorer PFS(P=0.366).Conclusions This study has established a method utilizing commonly used clinical parameters to distinguish very high-risk GISTs in clinical practice.However,further validation through multicenter studies with larger sample sizes is still required.

Objective:To investigate the effects of long intergenic non-coding RNA00894(LINC00894)on the malignant biological behaviors of gastric cancer(GC)cells via regulating the microRNA-205-5p(miR-205-5p)/glycoprotein non-metastatic melanoma protein B(GPNMB)axis.Methods:Twenty-five pairs of gastric cancer tissues and corresponding adjacent tissues were collected from patients undergoing surgical resection at the First Hospital of Hebei Medical University between November 2022 and September 2023.BGC823 cells were routinely cultured and into control,sh-NC,sh-LINC00894,sh-LINC00894+anti-NC,and sh-LINC00894+anti-miR-205-5p groups,followed by corresponding plasmids transfection using transfection reagents.The mRNA expression of LINC00894,miR-205-5p,and GPNMB in BGC823 cells and cancer tissues of each group was detected using qPCR.Dual luciferase reporter gene assay and AGO2-RNA immunoprecipitation were used to verify the targeted binding relationships between LINC00894 and miR-205-5p,as well as between miR-205-5p and GPNMB.Colony formation assay,EdU staining,wound-healing assay,and Transwell assay were performed to detect cell proliferation,migration and invasion abilities.Western blotting was used to detect the protein expression of CDK1,MMP-2 and MMP-9 in each group of cells.A nude mouse xenograft model was established to determine the effect of LINC00894 knockdown on tumor growth,and immunohistochemistry was used to detect the protein expression of GPNMB in xenograft tissues.Results:LINC00894 and GPNMB were significantly upregulated in gastric cancer tissues and cells,while miR-205-5p was downregulated(both P<0.05).LINC00894 negatively regulated miR-205-5p,while miR-205-5p negatively regulated GPNMB(all P<0.05).Knocking down LINC00894 promoted miR-205-5p expression and inhibited GPNMB expression in BGC823 cells(all P<0.05).Additionally,LINC00894 knockdown suppressed the proliferation,migration and invasion abilities of BGC823 cells,as well as the protein expression of CDK1,MMP-2,and MMP-9(all P<0.05).Inhibition of miR-205-5p reversed these effects(all P<0.05).Knocking down LINC00894 inhibited the growth of BGC823 cell-transplanted tumors,promoted miR-205-5p expression,and inhibited GPNMB protein expression(all P<0.05).Conclusion:LINC00894 is highly expressed in gastric cancer tissues and cells,while miR-205-5p is downregulated.Knockdown of LINC00894 can regulate the expression of miR-205-5p/GPNMB pathway-related proteins in BGC823 cells,thereby inhibiting their malignant biological behaviors.

Objective To explore the alterations in gray matter volume(GMV)in adolescents with bipolar disorder(BD).Methods 36 BD patients(BD group)and 37 healthy controls(HC group)who underwent magnetic resonance imaging(MRI)for artificial visual inspection in Affiliated Hangzhou First People's Hospital,School of Medicine,Westlake University from September 2019 to December 2021 were selected.Structural MRI data were processed by using FreeSurferv6.0.0,and statistical analysis were conducted by using SPSS 26.0 and R language software.Receiver operating characteristic(ROC)curve were employed to assess the diagnostic efficacy of various brain regions.Results Compared to HC group,patients in BD group exhibited significant reductions in GMV in the right superior frontal gyrus,right nucleus accumbens,left insula,right lateral orbitofrontal cortex,and right medial orbitofrontal cortex(P＜0.05).ROC curve analysis indicated that area under the curve(AUC)for the right superior frontal gyrus and right nucleus accumbens were 0.739 and 0.712 respectively,while the combined AUC for multiple brain regions was 0.820.Conclusion Adolescents with BD show significant reductions in GMV in specific brain regions,provide reference for the early identification and pathological mechanism research of BD.