Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objectives:To investigate the effect of circular RNA (circRNA) hsa_circ_0019217 on the biological function of chorionic trophoblast cell line (HTR8/SVneo) and its mechanism in the occurrence of pre-eclampsia (PE).Methods:The circRNA expression database was used to analyze the differentially expressed circRNA in placental tissues of PE women. The expression levels of hsa_circ_0019217 and miR-526b-5p were detected by reverse transcription real-time fluorescent quantitative PCR (RT-qPCR), and the subcellular localization of hsa_circ_0019217 was detected by fluorescence in situ hybridization. The proliferation, migration and invasion of trophoblast cells were detected by cell counting kit-8 (CCK-8) assay and transwell assay. Western blot and enzyme-linked immunosorbent assay (ELISA) were used to verify the effects of hsa_circ_0019217, miR-526b-5p and decorin (DCN) on matrix metalloproteinase 2 (MMP2), tissue inhibitor of metalloproteinase 2 (TIMP2), placental growth factor (PlGF) and human chorionic gonadotropin (hCG) protein expression levels. Dual luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay were used to verify the interaction between hsa_circ_0019217, miR-526-5p and DCN.Results:(1) The analysis of circRNA expression database showed that the expression level of hsa_circ_0019217 was significantly increased in the placental tissues of PE women (fold change=67, P<0.05), and it was mainly located in the cytoplasm. (2) Knockdown of hsa_circ_0019217 promoted the proliferation, migration and invasion of HTR8/SVneo cells, increased the expression levels of MMP2 and PlGF, and decreased the expression levels of TIMP2 and hCG in HTR8/SVneo cells. (3) Hsa_circ_0019217 targeted adsorption of miR-526b-5p, and inhibition of miR-526b-5p reduced the proliferation, migration and invasion of HTR8/SVneo cells. The expression levels of MMP2 and PlGF in HTR8/SVneo cells were increased, and the expression levels of TIMP2 and hCG were decreased. Hsa_circ_0019217 knockdown and inhibiting miR-526b-5p could reverse the effect of hsa_circ_0019217 knockdown on promoting the proliferation, migration and invasion of HTR8/SVneo cells, and reversed the effect of hsa_circ_0019217 knockdown on the protein expression levels of MMP2, PlGF, TIMP2 and hCG. (4) miR-526b-5p targeted DCN in HTR8/SVneo cells, hsa_circ_0019217 knockdown reduced the expression level of DCN, and inhibiting miR-526b-5p increased the expression level of DCN. When hsa_circ_0019217 and miR-526b-5p were inhibited simultaneously, there was no significant change in the protein expression level of DCN. (5) Overexpression of miR-526b-5p promoted the proliferation, migration and invasion of HTR8/SVneo cells, while overexpression of DCN inhibited the proliferation, migration and invasion of HTR8/SVneo cells. Simultaneous overexpression of miR-526b-5p and DCN reversed the effects of miR-526b-5p overexpression on cell proliferation, migration and invasion. Overexpression of miR-526b-5p increased the expression levels of MMP2 and PlGF and decreased the expression levels of TIMP2 and hCG in HTR8/SVneo cells. Overexpression of DCN reduced the expression levels of MMP2 and PlGF and increased the expression levels of TIMP2 and hCG. Overexpression of miR-526b-5p and DCN reversed the effects of miR-526b-5p on the expression of these proteins. Conclusion:Hsa_circ_0019217 regulates the expression of DCN by adsorption of miR-526b-5p, thereby affecting the proliferation, migration and invasion of trophoblast cells and regulating the protein expression levels of MMP2, TIMP2, PlGF and hCG, which might be used as a target for early prevention of PE.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective:This study aimed to explore the utility of transcutaneous electrical acupoint stimulation (TEAS) combined with skin sympathetic response (SSR) in assessing the effectiveness of perigastric autonomic nerve preservation during radical gastrectomy.Methods:A retrospective cohort analysis was conducted involving 221 patients who underwent laparoscopic radical gastrectomy at the Department of Gastric Surgery, Taizhou People's Hospital, affiliated with Nanjing Medical University, between June 2022 and September 2024. The cohort comprised 109 patients who underwent laparoscopic radical total gastrectomy without autonomic nerve preservation (total gastrectomy without nerve preservation group). Additionally, 112 patients underwent laparoscopic radical distal gastrectomy, including 34 patients who received autonomic nerve preservation (nerve preservation group) and 78 patients who did not (without nerve preservation group). TEAS was administered at the Zusanli and Tianshu acupoints one day before and one day after surgery, during which SSR latency and voltage amplitudes in the upper and lower extremities were recorded and compared across groups. Differences in SSR latency and voltage amplitude between the nerve preservation and non-nerve preservation groups of the distal gastrectomy cohort were also analyzed. Further, TEAS was applied at the same acupoints for 15 minutes on the 1st, 2nd, and 3rd postoperative days, and changes in intestinal sounds and intestinal functional recovery time were monitored. Surgical parameters, including operative duration, intraoperative blood loss, and harvested lymph node, were documented. Postoperative inflammatory indicators, including interleukin-6 (IL-6), C-reactive protein (CRP), procalcitonin (PCT), and the incidence of anastomotic leakage, were evaluated. At three months postoperatively, gastroscopy was performed to assess residual gastric food and bile reflux. Additionally, the prognostic nutritional index (PNI) was evaluated across all patient groups.Results:Following total gastrectomy, TEAS of Zusanli combined with arms' SSR revealed a latency of (23 59.71±410.55) ms and a voltage amplitude of (0.43±1.67) mV; for the legs, latency was (2 596.88±369.01) ms and voltage amplitude was (0.25±0.08) mV. TEAS of Tianshu combined with arms' SSR demonstrated a latency of (2 746.47±224.37) ms and a voltage amplitude of (0.31±0.14) mV; for the legs, latency was (2 891.90±193.61) ms and voltage amplitude was (0.19±0.72) mV. Postoperative latency was significantly prolonged, and voltage amplitude was markedly reduced (all P < 0.01). In the distal gastrectomy with nerve preservation group, TEAS of Zusanli combined with arms' SSR showed a latency of (1 668.04±261.91) ms and a voltage amplitude of (0.78±0.26) mV; for the legs, latency was (1 568.86±220.09) ms and voltage amplitude was (0.61±0.24) mV. TEAS of Tianshu combined with arms' SSR demonstrated a latency of (1 519.36±206.99) ms and a voltage amplitude of (0.66±0.34) mV; for the legs, latency was (2 004.80±508.53) ms and voltage amplitude was (0.55±0.28) mV. In the distal gastrectomy without nerve preservation group, TEAS of Zusanli combined with arms' SSR revealed a latency of (2 385.95±710.27) ms and a voltage amplitude of (0.23±0.11) mV; for the legs, latency was (2 506.81±779.37) ms and voltage amplitude was (0.26±1.29) mV. TEAS of Tianshu combined with arms' SSR indicated a latency of (2 697.78±385.55) ms and a voltage amplitude of (0.21±0.14) mV; for the legs, latency was (2 949.14±506.61) ms and voltage amplitude was (0.17±0.11) mV. The group without nerve preservation exhibited significantly prolonged latencies and reduced voltage amplitudes (all P<0.01). No statistically significant differences were observed between the groups in operative time, intraoperative bleeding, the number of dissected lymph nodes, inflammatory indicators (IL-6, CRP, PCT) at 3 days postoperatively, or anastomotic leakage rates (all P>0.05). In the group without nerve preservation, bowel sounds on postoperative days 1, 2, and 3 were (0.36±0.58), (1.04±0.97), and (1.74±1.10) times/min, respectively, with bowel function recovery time of (62.24±9.91) hours. The PNI at 3 months postoperatively was (37.42±3.01). Incidences of food residue in the residual stomach and bile reflux were 21.79% (17/78) and 29.49% (23/78), respectively. In the group with nerve preservation, bowel sounds on postoperative days 1, 2, and 3 were (0.76±0.82), (2.03±1.34), and (3.71±1.27) times/min, respectively, with bowel function recovery time of (44.94±8.05) hours. The PNI at 3 months postoperatively was (41.34±3.40). Incidences of food residue and bile reflux were 5.88% (2/34) and 11.76% (4/34), respectively. Statistically significant differences were observed between the groups (all P < 0.05). Conclusion:TEAS of Zusanli and Tianshu combined with SSR provides an objective measure for assessing the preservation of perigastric autonomic nerves during radical gastrectomy.

As a pharmaceutical excipient with low caloric value, low hygroscopicity, and high stability, mannitol is widely used in various dosage forms, such as solid, lyophilized and inhalation preparations, etc. It has different crystal structures (α, β and δ) and cocrystal, and the changes in the crystal structure will affect formulation properties of pharmaceutical formulations. This paper reviews structural features, physicochemical properties, and preparation methods of mannitol polymorphs and cocrystal formation, with emphasis on polymorphic transformation pathways, monitoring methods and the effect of polymorphic transformation on properties and application in pharmaceutical formulations, including tabletability, disintegration and dissolution properties. By systematically summarizing the crystallographic study of mannitol, this study attempts to provide new ideas for the development of novel pharmaceutical excipients and applications in pharmaceutical formulations.

As a pharmaceutical excipient with low caloric value, low hygroscopicity, and high stability, mannitol is widely used in various dosage forms, such as solid, lyophilized and inhalation preparations, etc. It has different crystal structures (α, β and δ) and cocrystal, and the changes in the crystal structure will affect formulation properties of pharmaceutical formulations. This paper reviews structural features, physicochemical properties, and preparation methods of mannitol polymorphs and cocrystal formation, with emphasis on polymorphic transformation pathways, monitoring methods and the effect of polymorphic transformation on properties and application in pharmaceutical formulations, including tabletability, disintegration and dissolution properties. By systematically summarizing the crystallographic study of mannitol, this study attempts to provide new ideas for the development of novel pharmaceutical excipients and applications in pharmaceutical formulations.

Objectives:To investigate the effect of circular RNA (circRNA) hsa_circ_0019217 on the biological function of chorionic trophoblast cell line (HTR8/SVneo) and its mechanism in the occurrence of pre-eclampsia (PE).Methods:The circRNA expression database was used to analyze the differentially expressed circRNA in placental tissues of PE women. The expression levels of hsa_circ_0019217 and miR-526b-5p were detected by reverse transcription real-time fluorescent quantitative PCR (RT-qPCR), and the subcellular localization of hsa_circ_0019217 was detected by fluorescence in situ hybridization. The proliferation, migration and invasion of trophoblast cells were detected by cell counting kit-8 (CCK-8) assay and transwell assay. Western blot and enzyme-linked immunosorbent assay (ELISA) were used to verify the effects of hsa_circ_0019217, miR-526b-5p and decorin (DCN) on matrix metalloproteinase 2 (MMP2), tissue inhibitor of metalloproteinase 2 (TIMP2), placental growth factor (PlGF) and human chorionic gonadotropin (hCG) protein expression levels. Dual luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay were used to verify the interaction between hsa_circ_0019217, miR-526-5p and DCN.Results:(1) The analysis of circRNA expression database showed that the expression level of hsa_circ_0019217 was significantly increased in the placental tissues of PE women (fold change=67, P<0.05), and it was mainly located in the cytoplasm. (2) Knockdown of hsa_circ_0019217 promoted the proliferation, migration and invasion of HTR8/SVneo cells, increased the expression levels of MMP2 and PlGF, and decreased the expression levels of TIMP2 and hCG in HTR8/SVneo cells. (3) Hsa_circ_0019217 targeted adsorption of miR-526b-5p, and inhibition of miR-526b-5p reduced the proliferation, migration and invasion of HTR8/SVneo cells. The expression levels of MMP2 and PlGF in HTR8/SVneo cells were increased, and the expression levels of TIMP2 and hCG were decreased. Hsa_circ_0019217 knockdown and inhibiting miR-526b-5p could reverse the effect of hsa_circ_0019217 knockdown on promoting the proliferation, migration and invasion of HTR8/SVneo cells, and reversed the effect of hsa_circ_0019217 knockdown on the protein expression levels of MMP2, PlGF, TIMP2 and hCG. (4) miR-526b-5p targeted DCN in HTR8/SVneo cells, hsa_circ_0019217 knockdown reduced the expression level of DCN, and inhibiting miR-526b-5p increased the expression level of DCN. When hsa_circ_0019217 and miR-526b-5p were inhibited simultaneously, there was no significant change in the protein expression level of DCN. (5) Overexpression of miR-526b-5p promoted the proliferation, migration and invasion of HTR8/SVneo cells, while overexpression of DCN inhibited the proliferation, migration and invasion of HTR8/SVneo cells. Simultaneous overexpression of miR-526b-5p and DCN reversed the effects of miR-526b-5p overexpression on cell proliferation, migration and invasion. Overexpression of miR-526b-5p increased the expression levels of MMP2 and PlGF and decreased the expression levels of TIMP2 and hCG in HTR8/SVneo cells. Overexpression of DCN reduced the expression levels of MMP2 and PlGF and increased the expression levels of TIMP2 and hCG. Overexpression of miR-526b-5p and DCN reversed the effects of miR-526b-5p on the expression of these proteins. Conclusion:Hsa_circ_0019217 regulates the expression of DCN by adsorption of miR-526b-5p, thereby affecting the proliferation, migration and invasion of trophoblast cells and regulating the protein expression levels of MMP2, TIMP2, PlGF and hCG, which might be used as a target for early prevention of PE.