ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids （MA） in ameliorating depression by network pharmacology， molecular docking， and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. Protein-protein interaction （PPI） network was constructed by protein interaction analysis （STRING） database. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed through Bioinformatics （DAVID） database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone （CORT） once a day for 35 consecutive days. Sixty mice were randomly allocated into control （0.9% normal saline）， model （CORT， 20 mg·kg^-1）， positive control （fluoxetine hydrochloride， 3.6 mg·kg^-1）， and MA （10， 5， and 2.5 mg·kg^-1） groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling （TUNEL） was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor （BDNF）， dopamine （DA）， 5-hydroxytryptamine （5-HT）， and norepinephrine （NE） in mice. The mRNA levels of cyclic adenosine monophosphate （cAMP） pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 （Cx43）. ResultsA total of 434 component targets and 545 depression targets were obtained， including 84 common targets， among which 10 core targets were screened out. GO analysis predicted 34 biological processes， 15 cell components， and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group， CORT prolonged the immobility time of mice in forced swimming and tail suspension tests （P<0.01）， lowered the serum levels of NE， BDNF， and 5-HT （P<0.05）， up-regulated the mRNA levels of nuclear factor-κB （NF-κB） and interleukin-6 （IL-6） in the brain tissue （P<0.05）， and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein （CREB） and BDNF （P<0.05） and the protein levels of protein kinase （PRKACA）， phosphorylation （p）-CREB/CREB， BDNF， and Cx43 （P<0.05） in the brain tissue. Compared with the model group， high-dose MA reduced the immobility time of mice in forced swimming （P<0.05） and tail suspension （P<0.01） tests， raised the serum levels of NE， BDNF， and 5-HT （P<0.01）， down-regulated the mRNA level of NF-κB （P<0.01）， and up-regulated the mRNA level of BDNF （P<0.01） and protein levels of PRKACA， p-CREB/CREB， BDNF， and Cx43 （P<0.05）. ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway， improving synaptic plasticity and gap junction function， and reducing neuroinflammation.

ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids （MA） in ameliorating depression by network pharmacology， molecular docking， and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. Protein-protein interaction （PPI） network was constructed by protein interaction analysis （STRING） database. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed through Bioinformatics （DAVID） database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone （CORT） once a day for 35 consecutive days. Sixty mice were randomly allocated into control （0.9% normal saline）， model （CORT， 20 mg·kg^-1）， positive control （fluoxetine hydrochloride， 3.6 mg·kg^-1）， and MA （10， 5， and 2.5 mg·kg^-1） groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling （TUNEL） was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor （BDNF）， dopamine （DA）， 5-hydroxytryptamine （5-HT）， and norepinephrine （NE） in mice. The mRNA levels of cyclic adenosine monophosphate （cAMP） pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 （Cx43）. ResultsA total of 434 component targets and 545 depression targets were obtained， including 84 common targets， among which 10 core targets were screened out. GO analysis predicted 34 biological processes， 15 cell components， and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group， CORT prolonged the immobility time of mice in forced swimming and tail suspension tests （P<0.01）， lowered the serum levels of NE， BDNF， and 5-HT （P<0.05）， up-regulated the mRNA levels of nuclear factor-κB （NF-κB） and interleukin-6 （IL-6） in the brain tissue （P<0.05）， and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein （CREB） and BDNF （P<0.05） and the protein levels of protein kinase （PRKACA）， phosphorylation （p）-CREB/CREB， BDNF， and Cx43 （P<0.05） in the brain tissue. Compared with the model group， high-dose MA reduced the immobility time of mice in forced swimming （P<0.05） and tail suspension （P<0.01） tests， raised the serum levels of NE， BDNF， and 5-HT （P<0.01）， down-regulated the mRNA level of NF-κB （P<0.01）， and up-regulated the mRNA level of BDNF （P<0.01） and protein levels of PRKACA， p-CREB/CREB， BDNF， and Cx43 （P<0.05）. ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway， improving synaptic plasticity and gap junction function， and reducing neuroinflammation.

Breast cancer is the most common malignant tumor among women, and early diagnosis, coupled with optimized treatment strategies is crucial for improving the prognosis. In recent years, with the advancement of nanotechnology, manganese-based nanomaterials have shown potential in various aspects of early breast cancer diagnosis, drug delivery, and tumor treatment. Compared to other nanomaterials, manganese-based nanomaterials exhibit excellent biocompatibility and have become a significant focus in the research of breast cancer diagnosis and treatment.

Objective:To investigate the strategies and clinical effects of free tissue flaps in repairing massive destructive burn wounds.Methods:This study was a retrospective observational study. From June 2014 to October 2023, 51 burn patients with 53 massive destructive burn wounds which met the inclusion criteria were admitted to Tongren Hospital of Wuhan University & Wuhan Third Hospital, including 47 males and 4 females, aged 21 to 77 years. After debridement, the wound area needed to be repaired by tissue flaps ranged from 20.0 cm×12.5 cm to 50.0 cm×15.0 cm. Emergency, early, or delayed transplantation of tissue flaps was performed to repair the wounds. Six head, face, and neck wounds, 5 upper limb wounds, and 1 lower limb wound were repaired with latissimus dorsi myocutaneous flaps. Eleven upper limb wounds and 6 lower limb wounds were repaired with anterolateral thigh flaps. Seven upper limb wounds, 5 lower limb wounds, and 2 face and neck wounds were repaired with paraumbilical perforator flaps. One lower limb wound was repaired with lower abdominal flap. Two face and neck wounds, 2 upper limb wounds, and 1 lower limb wound were repaired with inguinal flaps. One upper limb wound was repaired with scapular flap. One trunk wound was repaired with the "fillet flap" from the abandoned upper limb after amputation. Three head, face, and neck wounds, 3 lower limb wounds, and 1 upper limb wound were repaired with omental flaps. Four wounds were repaired by combined transplantation of the above-mentioned tissue flaps. Three wounds were repaired by fractional transplantation of the above-mentioned tissue flaps. The size of a single harvested tissue flap ranged from 15.0 cm×5.0 cm to 45.0 cm×25.0 cm. The arterial and venous anastomoses were added as the circumstances might require to improve tissue flap circulation. The wounds in the flap donor sites were sutured directly or repaired by split-thickness skin grafts from head. The general condition of patients during treatment was recorded. After surgery, the survival of tissue flaps, the healing of wounds in the recipient sites, limb salvage, the healing of wounds in the flap donor sites, and the survival of skin grafts were observed. The healing of wounds in the recipient sites was observed during follow-up. At the last follow-up, the upper limb function after successful limb salvage was evaluated by the Arm, Shoulder, and Hand Disability Scoring Scale, the weight-bearing walking ability of patients with successful lower limb salvage was evaluated by the Holden walking ability classification, and the patient's satisfaction with the efficacy was assessed by 5-grade Likert scale.Results:During treatment, one case with electrical burn of the head suffered from aggravated cerebral edema, cerebral hernia and coma recurred. After dehydration, hormone therapy, and so on, the patient recovered and incomplete hemiplegia on the right limb was left. The shock symptoms of 4 patients got worse, which were gradually controlled after anti-shock with fluid supplement and colloid injection. One patient developed hemorrhagic shock after tissue flap transplantation, which was corrected by fluid infusion and red blood cell suspension transfusion. Vascular crisis occurred in 3 tissue flaps after surgery, of which 2 survived and 1 eventually became necrotic after exploration. Partial necrosis occurred in 2 tissue flaps and slight necrosis occurred at the edge of 5 tissue flaps, which all healed after tissue flap trimming, vacuum sealing drainage (VSD), and skin grafting treatment. All the other tissue flaps survived. There were 12 recipient wounds with residual necrotic tissue after surgery, which healed after debridement, VSD, and skin grafting treatment. The remaining 41 wounds healed well. Among the 40 limb wounds of 39 patients, 5 patients had 3 upper limb and 2 lower limb amputations. The remaining 35 limbs of 34 patients were successfully salvaged. The donor site wounds healed well, and the skin grafts survived well. During the follow-up of 6 to 52 months, all the head, face, neck, and trunk wounds were well repaired. The fester recurred in 7 limb wounds 3 to 9 months after surgery and healed after debridement, drainage, and tissue flap repair. At the last follow-up, the functional scores of 22 upper limbs after successful limb salvage ranged from 0 to 100 (with an average of 50), and the Holden walking ability classification of 12 patients with 13 lower limbs after successful limb salvage was level Ⅴ in 8 cases, level Ⅳ in 2 cases, and level Ⅲ in 2 cases. The patients were very satisfied with the efficacy in 33 cases, relatively satisfied in 12 cases, and not quite satisfied in 6 cases.Conclusions:Systematic evaluation and treatment of the whole body condition, choosing the appropriate repair time, and using appropriate tissue flaps to repair massive destructive burn wounds will help ensure the safety of treatment, improve the repair effect, and reduce the injury of donor sites, thus optimizing the repair effect.

Objective To analyze the situation of life sciences and medical research involving human subjects conducted in a public hospital in Ningxia from 2020 to 2022 and explore the problems in the current management of such research and pro-vides suggestions for improvement.Methods Data were collected from research project application documents,task assign-ments,progress reports,final reports,and statistical tables of clinical drug trials conducted in the hospital from 2021 to 2022.Statistical analysis was performed on the life sciences and medical research involving human subjects.Results The number of research projects involving human subjects in the hospital increased annually from 2020 to 2022,accounting for more than 50%of the total projects.Over the three years,the sample size exceeded 100,000,and the number of projects with a cumulative collec-tion of more than 3,000 individuals showed an upward trend.However,the project registration rate was less than 10%.These types of research involve a large number of biological samples and information data,which have research value.However,re-searchers lack awareness of project registration,highlighting the need for greater attention from the hospital.Conclusion It is a trend to explore the medical value of this type of research in depth.The hospital should closely follow relevant national and re-gional policies,conduct dynamic monitoring and evaluation,and enhance supervision and management capabilities as a key factor in protecting biological samples and information data.This study also provides reference for other public hospitals in carrying out related regulatory work.

Objective To explore the molecular mechanism of N6-methyladenosine(m6A)methylation mediated by methyltransferase 3(METTL3)in regulating lipopolysaccharide(LPS)-induced endothelial cell permeability changes.Methods Human umbilical vein endothelial cells(HUVECs)were cultured in vitro.HUVECs were treated with LPS 50,125,250,500,1 000,2 000 ng/ml for 24 h.METTL3 mRNA expression was detected by Real-time PCR.After HUVECs were intervened with 500 ng/ml for 24 h,the methylation level of m6A was detec-ted,and cell permeability was measured by cell permeability test.Real-time PCR and Western blot were used to detect mRNA and protein expression of intercellular junction proteins(Claudin-5,Occludin and VE-caherin).METTL3 overexpressed stable cell lines were constructed to measure the changes of m6A methylation level and per-meability of endothelial cells during METTL3 overexpression.Results Compared to the control group,LPS inhibi-ted the expression of HUVECs METTL3 mRNA,decreased the methylation of m6A,increased the cell permeabili-ty,and decreased the mRNA and protein expression of intercellular junction proteins(Claudin-5,Occludin and VE-Caherin).When METTL3 was overexpressed,the m6A methylation levels of endothelial cells were enhanced,and the increase of endothelial cell permeability induced by LPS was reversed.Conclusion METTL3-mediated m6A methylation can improve the permeability of endothelial cells induced by sepsis.

Objective:To evaluate the effect of ultrasound-guided adductor canal block with bupivacaine liposome on analgesia in elderly patients undergoing total knee arthroplasty.Methods:This was a prospective study. Sixty American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ patients, regardless of gender, aged 65-83 yr, weighing 50-80 kg, scheduled for elective unilateral total knee arthroplasty under subarachnoid anesthesia from April 2023 to January 2024 in Zhengzhou Orthopaedic Hospital, were divided into 2 groups ( n=30 each) using a random number table method: bupivacaine liposome group (LB group) and ropivacaine group (R group). Ultrasound-guided adductor canal block was performed at 30 min before subarachnoid anesthesia, bupivacaine liposome diluent 20 ml (133 mg) was injected in LB group, and 0.5% ropivacaine 20 ml was injected in R group. Patient-controlled intravenous analgesia was performed after operation, and tramadol was used for rescue analgesia when the visual analogue scale (VAS) score ≥3. VAS scores at rest and during activity were recorded at 8, 12, 24, 48 and 72 h after surgery. The time to the first pressing analgesia pump and rescue analgesia were recorded within 72 h after surgery. The quadriceps muscle strength was measured at 1 day before surgery and 12, 24, 48 and 72 h after surgery. The knee joint range of motion was assessed at 1 day before surgery and 24, 48 and 72 h after surgery. Patient′s satisfaction with analgesia was recorded at 72 h after surgery. The adverse reactions within 72 h after surgery were also recorded. Results:Compared with R group, VAS scores at rest and during activity were significantly decreased at 12, 24, 48 and 72 h after surgery, the time to the first pressing analgesia pump was prolonged, the rate of rescue analgesia after surgery was decreased, the score for the patient′s satisfaction with analgesia was increased, the knee joint range of motion was increased ( P<0.05), and no significant change was found in the quadriceps muscle strength and incidence of adverse reactions in LB group ( P>0.05). Conclusions:Ultrasound-guided adductor canal block with bupivacaine liposome provides better analgesia than ropivacaine in elderly patients undergoing total knee arthroplasty.

Objective:To investigate the clinical effects of free transplantation of inguinal flap in repairing electrical burn wounds of mice in the limbs.Methods:A retrospective observational study was conducted. From January 2012 to May 2023, 24 male patients with electrical burns in the limbs meeting the inclusion criteria, aged 20 to 69 years, were admitted to the Department of Burns of Tongren Hospital of Wuhan University & Wuhan Third Hospital. Totally 27 limbs were involved, including 18 upper limbs and 9 lower limbs. After debridement, the wound area in the limbs proposed to be repaired with the inguinal flap was 5.0 cm×1.5 cm-20.0 cm×9.0 cm. A total of 26 operations were performed in 24 patients, and 27 free inguinal flaps with area being 5.0 cm×3.5 cm-22.0 cm×12.0 cm were resected, including 6 for lobed transplantation, 2 for chimeric transplantation with iliac bone graft, 3 for conjoined transplantation with pedicled latissimus dorsi myocutaneous flap, and 1 for conjoined transplantation with free paraumbilical perforator flap. Indocyanine green angiography was used to evaluate the blood supply of the inguinal flap during operation, to guide arterial supercharge during transplantation. Among the transplanted inguinal flaps, 5 were pedicled with the common trunk of the superficial circumflex iliac artery and the superficial abdominal wall artery, 13 were pedicled with the superficial circumflex iliac artery alone, 6 were pedicled with the superficial abdominal wall artery alone, and the remaining 3 were simultaneously anastomosed with the superficial circumflex iliac artery and the superficial abdominal wall artery for arterial supercharge. In another patient, the deep branch of the superficial circumflex iliac artery was used as a bridging vessel to recanalize the proper artery of the index finger in the distal segment. The wound in the donor area were sutured directly. The blood supply status of the inguinal flap immediately after resection but before cutting off blood vessels and after transplantation and vascular anastomosis was recorded. The survival of the tissue flap, the fixation of the iliac bone graft, and the healing of secondary defect in the donor area were observed after surgery. The appearance of the inguinal flap and the functional recovery of the recipient area were followed up. At the last follow-up, the function of the affected upper limb was scored using the Arm, Shoulder, and Hand Disability (DASH) scoring scale, and the satisfaction of patients with the efficacy of each surgical treatment was investigated by referring to the 5-level Likert scale.Results:Totally 27 inguinal flaps showed good arterial blood perfusion and venous return immediately after resection but before cutting off blood vessels and after transplantation and vascular anastomosis. Except for one inguinal flap that developed necrosis 12 days after operation and was repaired by split-thickness skin graft from the head, the remaining 26 inguinal flaps and conjointly transplanted tissue flaps survived completely without vascular crisis. The iliac bone graft was fixed securely after operation. All secondary defects in donor area healed well after operation. After 6 to 36 months of follow-up, the inguinal flap was soft in texture, without obvious swelling, the function of the recipient area was significantly improved as compared with that before surgery, and the protective feeling of the inguinal flap was restored. At the last follow-up, the functional scores of DASH scoring scale of the 18 affected upper limbs ranged from 0 to 100 (with a mean of 27). The patients were very satisfied with the efficacy of 17 surgical treatments and relatively satisfied with the efficacy of 9 surgical treatments.Conclusions:The donor area of the inguinal flap is concealed, and the damage resulted from flap resection in this area is small. This flap has a rich blood supply. In the electrical burn wounds of mice in the limbs repaired with lobed transplantation, chimeric transplantation, and conjoined transplantation with other flaps, the appearance and function of the recipient area are well restored, and the patients' satisfaction with the efficacy of surgical treatment is high, which is worthy of clinical promotion.

Objective:This study aimed to evaluate the efficacy of decitabine (DAC) and identify factors influencing treatment responses in patients with primary immune thrombocytopenia (ITP) who had failed glucocorticoid therapy.Methods:Clinical data of 61 patients with glucocorticoid-resistant ITP who received DAC therapy (5 mg·m -2·d -1×3 d via intravenous infusion) for at least three cycles with 3-4-week intervals at the Department of Hematology, Qilu Hospital of Shandong University, from November 2015 to June 2021 were analyzed retrospectively. Results:The 61 patients comprised 20 males and 41 females, with a median age of 45 years (range: 15-81 years). Among them, 43 patients were glucocorticoid-dependent (glucocorticoid-dependent group), while 18 patients were glucocorticoid-resistant (glucocorticoid-resistant group). Following DAC treatment, 12 patients (19.67% ) achieved complete response (CR), and 16 patients (26.23% ) exhibited response (R), resulting in an overall response (OR) rate of 45.90% (28/61). Comparison between the OR group ( n=28) and the non-response (NR) group ( n=33) revealed significant differences in responses to glucocorticoids (dependent or resistant) and platelet counts before treatment ( χ2=8.789, P=0.003; z=-2.416, P=0.016). The glucocorticoid-dependent group showed higher platelet counts than the glucocorticoid-resistant group after the second and third cycles of DAC treatment ( P=0.032, 0.024). Moreover, the OR rates after the first, second, and third cycles of DAC treatment in the glucocorticoid-dependent group were all higher than those in the glucocorticoid-resistant group ( P=0.042, P=0.012, P=0.029). A significant correlation was observed between glucocorticoid dependence and responses to DAC treatment ( OR=9.213, 95% CI 1.937-43.820, P=0.005) . Conclusion:DAC demonstrates definitive efficacy with mild adverse effects in a subset of patients with glucocorticoid-resistant primary ITP. Glucocorticoid dependence and higher platelet counts before treatment are associated with a favorable response to DAC therapy.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.