AIM: To explore the dynamic expression of high mobility group box 1(HMGB1)in scar tissues after glaucoma drainage valve implantation, and to further reveal the role and possible mechanism of HMGB1 in scarring after glaucoma surgery.METHODS: A total of 60 New Zealand white rabbits were randomly divided into control group(n=20), model group(n=20, silicone implantation under conjunctival sac)and model with drug administration group(n=20, silicone implantation under conjunctival sac combined with 5-fluorouracil injection). The conjunctival tissues were collected at 4 and 8 wk after surgery. HE staining and Masson staining were used to detect the proliferation and distribution of fibroblasts and collagen fibers in conjunctival tissues. Immunohistochemistry was utilized to detect the distribution and changes of HMGB1, transforming growth factor(TGF)-β1, Smad3 and α-smooth muscle actin(SMA)in conjunctival tissues. RT-PCR and Western blot were adopted to detect the mRNA and protein expression of HMGB1, TGF-β1, Smad3 and α-SMA in conjunctival tissues.RESULTS: HE staining and Masson staining showed that the proliferation of inflammatory cells, fibroblasts and collagen fibers in the model group was significantly higher than that in the control group at both 4 and 8 wk. Meanwhile, the proliferation of fibroblasts and collagen fibers in the model with drug administration group was significantly lower than that in the model group. Immunohistochemical staining showed that the expression of HMGB1, TGF-β1, Smad3 and α-SMA protein was observed in the conjunctival tissues of the model group both 4 and 8 wk, with brown and significantly deeper staining of the model group at 8 wk. Meanwhile, the positive staining in the model with drug administration group at both 4 and 8 wk was significantly lower than that in the model group. There was positive correlations between the number of fibroblasts stained with HE and the expression of HMGB1 in the conjunctival tissue of the model group at both 4 and 8 wk(r=0.602, 0.703, all P<0.05). RT-PCR and Western blot revealed that the mRNA and protein expression levels of HMGB1, TGF-β1, Smad3 and α-SMA in the model group were significantly higher than those in the control group at both 4 and 8 wk(all P<0.05). Meanwhile, the mRNA and protein expression levels of HMGB1, TGF-β1, Smad3 and α-SMA in the model with drug administration group were significantly lower than those in the model group(all P<0.05). There was positive correlations between mRNA expressions of HMGB1 and TGF-β1, Smad3 in the model group and the model with drug administration group(all P<0.05).CONCLUSION: The expression of HMGB1 increased at a time-dependent manner after glaucoma valve implantation. HMGB1 acts an indispensable role in the initiation and progression of scar formation after glaucoma surgery, which may be involved in the regulation of TGF-β/Smad signaling pathway.

Objective To analyze the influence of midazolam and propofol on sedation effect and blood gas indicators in elderly patients undergoing mechanical ventilation after cardiopulmonary bypass(CPB)cardiac surgery.Methods The elderly patients with mechanical ventilation after CPB cardiac surgery were grouped according to cohort method,including midazolam group(group M),propofol group(group P)and midazolam-propofol combined administration group(group M-P).Group M was treated with midazolam(intravenous injection of 0.05-0.10 mg kg-1 midazolam for sedation induction,and then continuously intravenous injection of 0.05-0.15 mg·kg-1·h-1 midazolam by micropump),and group P was treated with propofol(intravenous injection of 0.5 mg·kg-1 propofol for sedation induction,and then continuously intravenous injection of 0.5-2.0 mg·kg-1·h-1 propofol by micropump),and group M-P was given combined administration of midazolam and propofol(intravenous injection of 0.02-0.05 mg·kg-1 midazolam and 0.2-0.5 mg·kg-1 propofol for sedation induction and then continuously intravenous pump of 0.05-0.1 mg·kg-1 midazolam and 0.5-0.8 mg·kg·h-1 propofol).The sedation effect,blood gas indicators,hemodynamic indicators,extubation time,intensive care unit(ICU)stay time and treatment cost were compared among the three groups,and the adverse drug reactions during sedation therapy were recorded.Results There were 43 cases in group M,44 cases in group P,39 cases in group M-P.The drug onset times in groups M,P and M-P were(77.94±12.05),(18.18±5.20)and(21.25±9.36)s;the times to achieve satisfactory sedation effect were(42.57±11.41),(22.63±8.17)and(23.98±10.25)min;the recovery times after withdrawal were(59.30±14.86),(19.83±5.44)and(22.16±6.29)min;the extubation times were(1.61±0.20),(1.45±0.22)and(1.37±0.15)d;the ICU stay times were(2.17±0.29),(1.91±0.36)and(1.84±0.25)d;the treatment costs were(186.59±60.83),(922.97±164.34)and(375.03±71.16)thousand yuan;and the total incidence rates of adverse drug reactions were 34.88％,4.55％and 7.69％respectively,all with significant difference(all P＜0.05).There were no statistically significant differences in mean arterial pressure(MAP),heart rate(HR),oxygen saturation(SpO2),partial pressure of oxygen(PaO2),partial pressure of carbon dioxide(PaCO2)at T0,T1,T2,T3 and T4 among the three groups(all P＞0.05).Conclusion Combined administration of midazolam and propofol in elderly patients underwent mechanical ventilation after CPB cardiac surgery has a significant sedation effect,and it is conducive to reducing the dosages of sedative drugs,and it has small impact on blood gas indicators and hemodynamic indicators of patients.Compared with midazolam alone,it is more beneficial to shortening the extubation time and ICU stay and reducing the total incidence rate of adverse drug reactions,and compared with propofol alone,it is more beneficial to reducing treatment cost,and is a more ideal sedation administration model.

Objective To explore the clinical efficacy of double beam double tunnel enhanced reconstruction technique in the treatment of knee anterior cruciate ligament(ACL)training injuries.Methods Twenty-nine cases of ACL injury of knee joint from January 2021 to December 2021 were retrospectively analyzed.All the cases were underwent ligament reconstruc-tion surgery.Cases were grouped by surgical technique:there were 14 patients in conventional reconstruction group,including 13 males and 1 female,aged from 22 to 31 years old with an average of(27.07±7.28)years old,autogenous hamstring tendon was used for ligament reconstruction.There were 15 patients in the enhanced reconstruction group,including 13 males and 2 females,aged from 25 to 34 years old with an average of(29.06±4.23)years old,double tunnel ligament reconstruction,the autogenous hamstring muscle was used as the anteromedial bundle,and the posterolateral bundle was replaced by a high-strength line.The difference between knee tibial anterior distance,Lysholm score,International Knee Literature Committee(IKDC)subjective score,Tegner motor level score and visual analog scale(VAS)at 6th and 12th months after the surgery,limb symmetry index(LSI)were recorded at the last follow-up and surgery-related adverse effects during follow-up.Results All patients were followed up,ranged from 13 to 15 months with an average of(13.7±0.8)months.There were no serious adverse reactions related to surgery during the period.There was no statistical difference between the preoperative general data and the observation index of the two groups(P＞0.05).The difference in tibial anterior distance at 6 and 12 months in the enhanced re-construction group(1.45±0.62)mm and(1.74±0.78)mm which were lower those that in the conventional reconstruction group(2.42±0.60)mm and(2.51±0.63)mm(P＜0.05).There was no significant difference in postoperative Lysholm score,Tegner motor level score,IKDC score,VAS,and limb symmetry index at the last follow-up(P＞0.05).Conclusion The enhanced recon-struction technique can more effectively maintain the stability of the knee joint and has no significant effect on the postoperative knee joint function compared with the traditional ligament reconstruction technique.The short-term curative effect is satisfac-tory,and it is suitable for the group with high sports demand.

  Objective  This study aimed to investigate Chinese anesthesiologists' comprehension of palliative care and their experiences with palliative sedation for patients in the end-stage of life.  Methods  From October to December 2021, a national cross-sectional survey was conducted among anesthesiologists in China distributed by the Chinese Society of Anesthesiology, Chinese Medical Association with convenient sampling. The survey questionnaire encompassed general information, professional experience, familiarity with palliative care, emotional responses to end-stage cases, experience with sedation for critically ill or end-stage patients, and preferences for sedation medication.  Results  A total of 2536 anesthesiologists from 29 provinces in China completed valid questionnaires. Among them, 572 anesthesiologists(22.6%, 572/2536) reported familiarity with palliative medicine. Male anesthesiologists, as well as those with prior experience in caring for critically ill or end-stage patients, involved in pain management and practicing in hospitals with established institutional palliative care teams, demonstrated greater familiarity with palliative care concepts(all P<0.05). Over 40% of respondents felt powerless, helpless, and indecisive when confronted with end-stage patients. Anesthesiologists knowledgeable about palliative care exhibited greater confidence in managing critically ill or end-stage patients(9.8% vs. 4.4%, P=0.001). Among the anesthesiologists surveyed, 734 had administered sedation to end-stage patients, with 151 of them(20.6%, 151/734) inappropriately relying solely on opioids for sedation.  Conclusions  The understanding of palliative care and palliative sedation medication choice among anesthesiologists in China is still very limited. The establishment of palliative care teams, provision of education and training in palliative care, and enhancement of familiarity with palliative principles may bolster anesthesiologists' confidence when encountering critically ill or end-stage patients and subsequently enhance the quality of care for patients in the terminal stages of life.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Aging is an independent risk factor for chronic diseases in the elderly, and understanding aging mechanisms is one of the keys to achieve early prevention and effective intervention for the diseases. Aging process is dynamic and systemic, making it difficult for mechanistic study. With recent advances in aging biomarkers and development of live-imaging technologies, more and more reporter mouse models have been generated, which can live monitor the aging process, and help investigate aging mechanisms at systemic level and develop intervention strategies. This review summarizes recent advances in live-imaging aging reporter mouse models based on widely used aging biomarkers (p16^Ink4a, p21^Waf1/Cip1, p53 and Glb1), and discusses their applications in aging research.
Humans ; Animals ; Mice ; Aged ; Aging ; Cyclin-Dependent Kinase Inhibitor p16/metabolism* ; Cyclin-Dependent Kinase Inhibitor p21/metabolism* ; Biomarkers ; Tumor Suppressor Protein p53

BackgroundType 1 diabetes is caused by a chronic immune response that destroys islet beta cells， resulting in elevated blood glucose. Mesenchymal stem cells can prevent and treat the development of diabetes and its complications. However， little is known about the effects and potential mechanisms of Gingival mesenchymal stem cells （GMSCs） in preventing diabetes. The aim of this study is to investigate the mechanism of GMSCs in preventing type 1 diabetes in mice and to find targets for clinical treatment of diabetes. MethodsWe injected human GMSCs into NOD mice to observe the trend of blood glucose， observed the survival of pancreatic β-cells by immunohistochemistry， and detected the change of immune cells in the spleen of mice by flow analysis. Finally， the immune cells in NOD mice were transfused into NOD-SCID mice to observe the onset of diabetes in NOD-SCID mice. ResultsGMSCs significantly reduced the incidence of diabetes in NOD mice， with 64% of control mice developing diabetes at 27 weeks of age compared with 35% in the GMSC group， P=0.013. The percentage of Follicular B cells（FO B cell） in the spleen of GMSCs-treated mice decreased from （52.2±4.1）% to （43.2±5.3）%， P=0.008， while other types of immune cells did not change significantly. The immunohistochemical results showed that GMSCs could effectively improve the survival of pancreatic β-cells， which could continuously produce insulin to control blood glucose. Finally， we found the spleen cells transfusion could prevent the development of diabetes in NOD-SCID mice. ConclusionGMSCs can reduce diabetes in mice by reducing FO B cells in the spleen.

Chloral hydrate is a commonly used central sedative drug before pediatric clinical examination, but its clinical safety and medication adherence are needed to focus on normally because of its poor stability and palatability. Under the premise of investigating the stability of different formulations, their palatability were also screened by using both human sensory and electronic tongue evaluation techniques. Human sensory evaluation has been conducted with the informed consent of all participants in accordance with the ethical requirements of the Good Clinical Practice for Drug Trials. The results showed that the addition of sorbitol and sucralose could effectively ensure the stability of the oral solution. Sorbitol is the main taste-masking component, and the ratio of 40% sorbitol and 0.5% sucralose can effectively mask the bitterness, astringency and spicy taste of 10% chloral hydrate oral solution. The results detected by human sensory and electronic tongue have good correlation and complementarity, and the combination of these two methods is more conducive to getting objective and reasonable conclusions.

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

MicroRNAs (miRNAs) are mediators of the aging process. The purpose of this work was to analyze the miRNA expression profiles of spermatozoa from men of different ages with normal fertility. Twenty-seven donors were divided into three groups by age (Group A, n = 8, age: 20-30 years; Group B, n = 10, age: 31-40 years; and Group C, n = 9, age: 41-55 years) for high-throughput sequencing analysis. Samples from 65 individuals (22, 22, and 21 in Groups A, B, and C, respectively) were used for validation by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 2160 miRNAs were detected: 1223 were known, 937 were newly discovered and unnamed, of which 191 were expressed in all donors. A total of 7, 5, and 17 differentially expressed microRNAs (DEMs) were found in Group A vs B, Group B vs C, and Group A vs C comparisons, respectively. Twenty-two miRNAs were statistically correlated with age. Twelve miRNAs were identified as age-associated miRNAs, including hsa-miR-127-3p, mmu-miR-5100_L+2R-1, efu-miR-9226_L-2_1ss22GA, cgr-miR-1260_L+1, hsa-miR-652-3p_R+1, pal-miR-9993a-3p_L+2R-1, hsa-miR-7977_1ss6AG, hsa-miR-106b-3p_R-1, hsa-miR-186-5p, PC-3p-59611_111, hsa-miR-93-3p_R+1, and aeca-mir-8986a-p5_1ss1GA. There were 9165 target genes of age-associated miRNAs. Gene Ontology (GO) analysis of the target genes identified revealed enrichment of protein binding, membrane, cell cycle, and so on. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of age-related miRNAs for target genes revealed 139 enriched pathways, such as signaling pathways regulating stem cell pluripotency, metabolic pathways, and the Hippo signaling pathway. This suggests that miRNAs play a key role in male fertility changes with increasing age and provides new evidence for the study of the mechanism of age-related male fertility decline.
Humans ; Male ; Young Adult ; Adult ; Middle Aged ; MicroRNAs/genetics* ; Signal Transduction/genetics* ; Spermatozoa/metabolism* ; Gene Expression Profiling