AIM:To explore the effect of miR-1246 on high glucose-induced retinal microvascular endothelial cells(RMECs)injury by regulating methyltransferase like 3(METTL3)mediated sirtuin 1(SIRT1)N6-methyladenosine(m6A)modification.METHODS:Dual luciferase assay was used to detect miR-1246 regulation of METTL3 expression; RMECs cells were divided into control group, high glucose(HG)group, high glucose+knocking down control(HG+anti-miR-NC)group, high glucose+knocking down miR-1246 expression(HG+anti-miR-1246)group, high glucose+overexpression control(HG+NC)group, high glucose+overexpression METTL3(HG+METTL3)group, high glucose+overexpression miR-1246+control(HG+miR-1246+NC)group, and high glucose+overexpression miR-1246+METTL3(HG+miR-1246+METTL3)group. After induction of high glucose for 48 h, CCK-8 method was used to detect cell survival; Annexin V-FITC/PI method was used to detect cell apoptosis; Transwell experiment was used to detect cell migration and invasion; ELISA method was used to detect cell oxidative stress and inflammation levels; Colorimetric method was used to detect m6A methylation level in total RNA; MeRIP-qPCR method was used to detect SIRT1 m6A methylation level; Real-time quantitative PCR was used to detect miR-1246, METTL3, SIRT1 mRNA expression in cells; Western blot was used to detect METTL3, SIRT1 and endothelial mesenchymal transition(EndMT)markers protein expression in cells.RESULTS: The MiR-1246 regulated METTL3 expression. Compared with the control group, cell survival rate was decreased in the HG group, apoptosis rate was increased, and the number of migrating and invading cells were increased, lactate dehydrogenase(LDH)activity, tumor necrosis factor-α(TNF-α), and interleukin(IL)-6 levels in cell culture supernatant were increased, IL-10 level was decreased, malondialdehyde(MDA)level was increased, superoxide dismutase(SOD)activity was decreased, miR-1246 expression was increased, total RNA m6A level and SIRT1 m6A level were decreased, METTL3, SIRT1, cluster of differentiation 31(CD31)and vascular endothelial cadherin(VE-cadherin)expression were decreased, while Vimentin and Snail1 expression were increased(all P<0.05); compared with the HG+anti-miR-NC group, cell survival rate was increased in the HG+anti-miR-1246 group, apoptosis rate was decreased, and the number of migrating and invading cells were decreased, LDH activity, TNF-α, and IL-6 levels in cell culture supernatant were decreased, IL-10 level was increased, MDA level was decreased, SOD activity was increased, miR-1246 expression was decreased, total RNA m6A level and SIRT1 m6A level were increased, METTL3, SIRT1, CD31 and VE-cadherin expression were increased, while Vimentin and Snail1 expression were decreased(all P<0.05); compared with the HG+NC group, cell survival rate was increased in the HG+METTL3 group, apoptosis rate was decreased, and the number of migrating and invading cells were decreased, LDH activity, TNF-α, and IL-6 levels in cell culture supernatant were decreased, IL-10 level was increased, MDA level was decreased, SOD activity was increased, miR-1246 expression was decreased, total RNA m6A level and SIRT1 m6A level were increased, METTL3, SIRT1, CD31 and VE-cadherin expression were increased, while Vimentin and Snail1 expression were decreased(all P<0.05); compared with the HG+miR-1246+NC group, cell survival rate was increased in the HG+miR-1246+METTL3 group, apoptosis rate was decreased, and the number of migrating and invading cells were decreased, LDH activity, TNF-α, and IL-6 levels in cell culture supernatant were decreased, IL-10 level was increased, MDA level was decreased, SOD activity was increased, miR-1246 expression was decreased, total RNA m6A level and SIRT1 m6A level were increased, METTL3, SIRT1, CD31 and VE-cadherin expression were increased, while Vimentin and Snail1 expression were decreased(all P<0.05).CONCLUSION:The miR-1246 promotes high glucose-induced apoptosis, invasion and metastasis, oxidative stress, inflammatory response, and EndMT process in RMECs cells by regulating METTL3 mediated SIRT1 m6A modification.

Objective:To explore the clinical efficacy of the first dorsal metatarsal artery pedicled lateral toe bilobed flap in repairing the finger pulp defects of two adjacent fingers.Methods:This study was a retrospective observational study. From January 2018 to December 2022, 9 patients with finger pulp defects in two adjacent fingers who met the inclusion criteria were admitted to the Department of Burns and Plastic Surgery of the 988 th Hospital of Joint Logistics Support Force of PLA, including 6 males and 3 females, aged 26 to 48 years. The injured fingers were the index finger and middle finger (5 cases) or the middle finger and ring finger (4 cases). After debridement, the wound area of a single finger ranged from 1.2 cm×0.8 cm to 3.2 cm×2.8 cm. The finger pulp defects of two adjacent fingers were repaired with the first dorsal metatarsal artery pedicled lateral toe bilobed flap, and the two adjacent fingers were sutured together. The area of single flap ranged from 1.5 cm×1.0 cm to 3.5 cm×3.0 cm. The wound in the flap donor site was sutured directly or repaired with full-thickness skin graft from the groin region. The finger separation surgery was performed 3 weeks after surgery. The survival and blood supply of flaps, and survival of skin grafts and wound healing of the donor sites were observed after surgery. During follow-up, the texture, sliding, and shape of the flap, movement function of the finger, and the shape and function of the foot donor site were observed. At the last follow-up, the sensory of the flap was evaluated according to the sensory evaluation standard of the British Medical Research Council, and the hand function was evaluated according to the functional evaluation trial standard for severed finger replantation of the Hand Surgery Society of the Chinese Medical Association. Results:After surgery, all the flaps of 9 patients survived without vascular crisis. The flaps were soft in texture and good in shape. One patient had partial necrosis at the edge of the skin graft in the toe, and the wound healed after dressing change; the skin grafts in the toe in the other 8 patients survived, and the wounds healed well. During follow-up of 12 to 18 months after surgery, the flaps had soft texture, good elasticity, low sliding, and good shape. The finger movement function was normal. The wound in foot donor site recovered well without ulceration and deformity, and walking was not affected. At the last follow-up, the sensation of the flaps was sensitive, of which 8 flaps reached S3 and 10 flaps reached S3 + in sensation, and the two-point discrimination distance of the flaps was 9-13 mm. The functional scores of the affected fingers were 85 to 95, all of which were excellent. Conclusions:The first dorsal metatarsal artery pedicled lateral toe bilobed flap can repair finger pulp defects of two adjacent fingers at the same time, and the appearance, sensation, and function of the affected fingers recovered well after surgery, with less damage to the foot donor site. It is one of good methods to repair finger pulp defects of two adjacent fingers in clinic.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Objective:To explore the clinical efficacy of the first dorsal metatarsal artery pedicled lateral toe bilobed flap in repairing the finger pulp defects of two adjacent fingers.Methods:This study was a retrospective observational study. From January 2018 to December 2022, 9 patients with finger pulp defects in two adjacent fingers who met the inclusion criteria were admitted to the Department of Burns and Plastic Surgery of the 988 th Hospital of Joint Logistics Support Force of PLA, including 6 males and 3 females, aged 26 to 48 years. The injured fingers were the index finger and middle finger (5 cases) or the middle finger and ring finger (4 cases). After debridement, the wound area of a single finger ranged from 1.2 cm×0.8 cm to 3.2 cm×2.8 cm. The finger pulp defects of two adjacent fingers were repaired with the first dorsal metatarsal artery pedicled lateral toe bilobed flap, and the two adjacent fingers were sutured together. The area of single flap ranged from 1.5 cm×1.0 cm to 3.5 cm×3.0 cm. The wound in the flap donor site was sutured directly or repaired with full-thickness skin graft from the groin region. The finger separation surgery was performed 3 weeks after surgery. The survival and blood supply of flaps, and survival of skin grafts and wound healing of the donor sites were observed after surgery. During follow-up, the texture, sliding, and shape of the flap, movement function of the finger, and the shape and function of the foot donor site were observed. At the last follow-up, the sensory of the flap was evaluated according to the sensory evaluation standard of the British Medical Research Council, and the hand function was evaluated according to the functional evaluation trial standard for severed finger replantation of the Hand Surgery Society of the Chinese Medical Association. Results:After surgery, all the flaps of 9 patients survived without vascular crisis. The flaps were soft in texture and good in shape. One patient had partial necrosis at the edge of the skin graft in the toe, and the wound healed after dressing change; the skin grafts in the toe in the other 8 patients survived, and the wounds healed well. During follow-up of 12 to 18 months after surgery, the flaps had soft texture, good elasticity, low sliding, and good shape. The finger movement function was normal. The wound in foot donor site recovered well without ulceration and deformity, and walking was not affected. At the last follow-up, the sensation of the flaps was sensitive, of which 8 flaps reached S3 and 10 flaps reached S3 + in sensation, and the two-point discrimination distance of the flaps was 9-13 mm. The functional scores of the affected fingers were 85 to 95, all of which were excellent. Conclusions:The first dorsal metatarsal artery pedicled lateral toe bilobed flap can repair finger pulp defects of two adjacent fingers at the same time, and the appearance, sensation, and function of the affected fingers recovered well after surgery, with less damage to the foot donor site. It is one of good methods to repair finger pulp defects of two adjacent fingers in clinic.

OBJECTIVE To investigate the effect of bs-5-YHEDA iron chelating peptide combined with semaglutide on the cognitive ability and pathological characteristics of D-Gal-induced Alzheimer's disease(AD) model mice. METHODS Forty mice were randomly divided into 5 groups, namely the healthy control group, PBS group, bs-5-YHEDA iron chelating peptide group, combined treatment group and positive control group, with 8 mice in each group, half of each sex. Except for the healthy control group, D-galactose was injected to induce the AD mice model for 6 weeks. For 3 consecutive weeks starting from the 4th week, the bs-5-YHEDA iron chelating peptide group was injected with bs-5-YHEDA(1 mg·mL–1) once every other day at 200 µL in the tail vein; the bs-5-YHEDA iron chelating peptide(1 mg·mL–1) and semaglutide(25 nmol·kg–1·d–1) were given alternately once a day in the combination treatment group; the positive control group was given memantine(3.3 mg·kg–1·d–1) by gavage every other day. The healthy control group and PBS group were injected with the equal dose of PBS. At the end of treatment, the learning memory ability of mice was detected by the Morris water maze method, whole brain and whole blood were dissected, and pathological changes in hippocampal region were observed by HE staining, and Aβ expression and Tau protein phosphorylation levels were detected by immunohistochemistry, enzyme-linked immunosorbent assay and immunoblotting. RESULTS In the Morris water maze spatial exploration experiment, the differences in the number of times the mice traversed the platform, the ratio of swimming distance to the target quadrant, and the time ratio were statistically significant in each group(P<0.05); compared with the PBS group, the ratio of swimming distance to the target quadrant increased in the combined treatment group, and the differences were statistically significant(P<0.05). The results of HE staining showed that compared with the healthy control mice, the hippocampal area in the PBS group showed reduced levels of pyramidal cells, disorganized arrangement, cell edema, and deep staining of nuclei consolidation. Cellular disorganization, deep staining of nuclei and apoptosis in the hippocampus were significantly improved in each treatment group after drug treatment. Immunohistochemistry and Western blotting results showed that the Aβ expression levels and Tau protein phosphorylation levels were significantly higher in the PBS-administered mice compared with the healthy control mice, and the Aβ expression levels and Tau protein phosphorylation levels were reduced in each group after drug treatment, with statistically significant differences(P<0.01 or P<0.001 ). CONCLUSION The combination of bs-5-YHEDA iron chelating peptide and semaglutide can effectively improve the learning and memory ability and pathological characteristics of AD mice, but from the results of immunohistochemistry and immunoblotting experiments, the improvement of pathological characteristics of AD mice in the combination treatment group is not obvious compared with the single bs-5-YHEDA iron chelating peptide group, suggesting that there may be a threshold effect of our designed dual-target combination treatment on the cognitive improvement of AD mice, and the optimization and validation of the effect of multi-target combination treatment need further study.

Objective: To analyze the application of digital games for interventions to reduce risky sexual behavior among adolescents, so as to provide a reference for reducing adolescent risky sexual behavior. Methods: The study used PubMed, Web of Science, Cochrane Library, Scopus, Embase, China Biomedical Database, CNKI, Wanfang Database and VIP to carry out a literature search of the application of digital games for interventions aimed at reducing risky sexual behavior among adolescents covering the time period up until February 2024. Results: A total of 10 English articles were included, involving a total of 3 063 adolescents aged 10-24 years old. The publication time spanned from 2013 to 2023. The development and design of the digital games were mostly based on cognitive behavior theory and authentic decision making situations and dialogues. The game participants were divided into single party and multi party categories, mainly using virtual role playing, interactive narrative, and adventure challenges, and there were some differences in content. Digital game intervention had good feasibility and acceptability, which could improve adolescents sexual health knowledge, attitudes, self efficacy, and risk perception, so as to reduce the occurrence of risky behavior. Conclusion As an intervention aimed at reducing risky sexual behavior in adolescents, digital show has significant advantages and can serve as a new prevention and control strategy.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the risk factors for liver cancer after splenectomy in patients with cirrhosis.Methods:The clinical data of 150 patients diagnosed with hepatitis B associated cirrhosis, portal hypertension, and hypersplenism who underwent splenectomy at Shaanxi Provincial People's Hospital and the First Affiliated Hospital of Xi'an Jiaotong University from March 2000 to November 2012 were retrospectively analyzed. There were a total of 150 patients included, 114 males and 36 females, aged (44±10) years old. General information, intraoperative conditions, and postoperative complications of the patients were documented. The postoperative progress of patients was monitored by telephone or outpatient follow-up. Based on the follow-up results regarding liver cancer presence, all patients were categorized into two groups: liver cancer group ( n=42) and non-liver cancer group ( n=108). Multivariate analysis was employed to identify factors influencing the liver cancer occurrence after splenectomy. Kaplan-Meier survival analysis along with log-rank test was utilized to assess overall survival and survival rate comparison. Results:Compared to the non-liver cancer group, the liver cancer group exhibited an increased prevalence of hypertension, direct bilirubin levels, prothrombin time, maximum spleen diameter, and postoperative thrombosis (all P<0.05). However, there was a significant reduction in the number of patients receiving long-term regular antiviral therapy and postoperative bleeding (all P<0.05). The multivariate analysis revealed that preoperative hypertension ( OR=6.310, 95% CI: 1.729-23.024, P=0.005), spleen diameter exceeding 12 cm ( OR=5.338, 95% CI: 1.234-23.094, P=0.025), and occurrence of postoperative thrombosis ( OR=8.652, 95% CI: 2.700-27.729, P<0.001) in patients with hepatitis B-related liver cirrhosis and portal hypertension were associated with an increased risk of developing liver cancer following splenectomy. Patients who receive long-term regular antiviral treatment after surgery ( OR=0.143, 95% CI: 0.038-0.545, P=0.004) have a lower risk of developing liver cancer. There was no statistically significant difference observed in the cumulative survival rate between the liver cancer group and the non-liver cancer group ( χ2=1.74, P=0.187). Conclusion:Preoperative hypertension, spleen diameter exceeding 12 cm, and postoperative thrombosis are independent risk factors for liver cancer in patients with hepatitis B-related cirrhosis and portal hypertension after splenectomy. Additionally, postoperative long-term antiviral therapy serves as an independent protective factor.

Objective:To evaluate the value of metagenomic Next Generation Sequencing (mNGS) for the pathogenetic diagnosis of bloodstream infections in patients with sepsis.Methods:A retrospective analysis was performed on 105 sepsis cases who received blood mNGS and blood culture tests during their hospitalization in the Intensive Care Department of the Affiliated Hospital of North Sichuan Medical College from September 2021 to August 2023, and the results were compared and analyzed. According to mNGS and blood culture results, the cases were divided into the positive group and negative group.The distribution of pathogens in the enrolled patients were analyzed, and the diagnostic performance and consistency of blood culture and mNGS were compared. The differences in clinical characteristics of patients in each group were analyzed, and the pathogenic diagnostic value of mNGS for bloodstream infections in patients with sepsis was evaluated.Results:①Among 105 blood samples, 61 cases (58.10%) had positive results of mNGS, and 32 cases (30.48%) had positive results of blood culture. The positive rate of mNGS was higher than that of blood culture, and the difference was statistically significant ( P < 0.05).The accuracy of mNGS was lower than that of blood culture②The mean values of ESR, PCT and CRP in positive group were higher than those in negative group, and the proportion of septic shock was higher than that in negative group, and the differences were statistically significant ( P < 0.05). There was no significant difference in 28-day mortality rate between the two groups ( P > 0.05). Conclusions:mNGS is beneficial to the etiological diagnosis and treatment of bloodstream infection in patients with sepsis.

Objective:To explore the protective effect of zonisamide (ZNS) on oxygen-glucose deprivation (OGD) cell model of traumatic brain injury (TBI), and its underlying mechanism.Methods:Human neuroblastoma cells (SH-SY5Y) were cultured in vitro and divided into the control group, OGD group, and drug administration group (OGD+ZNS group) according to the random number table method. The OGD method was used to establish a TBI cell model. After modeling, the cell activity, the release of lactate dehydrogenase (LDH), and β-galactosidase staining were detected to evaluate cell function and senescence. Additionally, mitochondrial morphology and potential membrane changes were observed using Mito Tracker Red and JC-1 mitochondrial membrane potential staining. ATP concentration was measured, and protein was extracted from SH-SY5Y cells and then subjected to Western blot analysis to detect endoplasmic reticulum stress-related markers, including glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), protein disulfide isomerase (PDI), and β-actin.Results:The OGD group had a significantly lower cell survival rate compared to the control group ( P<0.01), while the OGD+ZNS group had a significant higher cell survival rate than the OGD group ( P<0.01). The LDH release rate was significantly higher in the OGD group than in the control group ( P<0.01), while the OGD+ZNS group had a significant lower LDH release rate compared to the OGD group ( P<0.01). Moreover, the cell staining results indicated that compared to the control and OGD+ZNS groups, the cells in the OGD group exhibited significant damage and senescence with darker staining while the mitochondrial staining results demonstrated a significant reduction in mitochondrial linear junctions and decreased mitochondrial activity in the OGD group compared to the control and OGD+ZNS groups. Compared to the control and OGD+ZNS groups, the OGD group exhibited a significant reduction in mitochondrial staining red fluorescence, a significant increase in green fluorescence, and a significant decrease in mitochondrial membrane potential. The OGD group demonstrated a significant decrease in ATP concentration compared to the control group ( P<0.01), whereas the OGD+ZNS group exhibited a significant higher ATP concentration compared to the OGD group ( P<0.01). Western blot analysis revealed significant upregulation of GRP78, CHOP, and PDI in the OGD group compared to the control group (all P<0.05), while in the OGD+ZNS group, the expression levels of these proteins were significantly downregulated compared to the OGD group (all P<0.05). Conclusions:Zonisamide can protect OGD TBI cell model by preserving mitochondrial activity and inhibiting endoplasmic reticulum stress.