ObjectiveTo investigate the effect of SU056， an azo-podophyllotoxin derivative， on carbon tetrachloride （CCl₄）-induced liver fibrosis in mice and related mechanisms of action. MethodsA total of 12 mice were randomly divided into control group， model group （CCl₄+normal saline）， and treatment group （CCl₄+SU056）， with 4 mice in each group. Mice were given intraperitoneal injection of CCl₄ to establish a model of liver fibrosis， and during the middle stage of modeling， the mice in the treatment group were given daily intraperitoneal injection of SU056. Liver histopathological injury， collagen deposition， and liver function were assessed based on HE staining， Masson staining， Sirius Red staining， the content of hydroxyproline in liver tissue， and the serum levels of alanine aminotransferase and aspartate aminotransferase， and immunofluorescence assay was used to measure the expression levels of smooth muscle actin α （α-SMA）， collagen type Ⅰ， and Y-box binding protein 1 （YB1）. The human hepatic stellate cell （HSC） line LX-2 and primary mouse HSC were used， and CCK-8 assay was used to measure cell proliferation； Transwell assay was used to observe cell migration； quantitative reverse transcription-polymerase chain reaction and Western Blot were used to measure the expression levels of collagen type Ⅰ， collagen type Ⅲ， YB1， phosphorylated mammalian target of rapamycin （mTOR）， and phosphorylated S6K， so as to validate the function of the YB1/mTOR signaling axis. The one-way or two-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsIn the mouse model of liver fibrosis induced by CCl₄， compared with the model group， the treatment group had significant alleviation of inflammatory cell infiltration， collagen deposition， and pseudolobule formation in liver tissue and significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of hydroxyproline in liver tissue （all P<0.01）. Immunofluorescence assay showed that SU056 significantly inhibited the abnormal high expression of α-SMA， collagen type I， and YB1 in liver tissue （all P<0.01）. In vitro experiments showed that SU056 inhibited the transforming growth factor-β1-induced proliferation of LX-2 cells （P<0.01）， the migration of LX-2 cells （P<0.05）， and the transcriptional up-regulation of collagen type Ⅰ and collagen type Ⅲ （all P<0.05） in a dose-dependent manner， and SU056 could inhibit the spontaneous activation of primary HSC in vitro. Mechanistic studies revealed that transforming growth factor-β1 simultaneously upregulated the expression levels of YB1， phosphorylated mTOR， and phosphorylated S6K in LX-2 cells， and treatment with SU056 （10 and 20 µmol/L） could downregulate the protein expression levels of collagen type I， YB1， phosphorylated mTOR， and phosphorylated S6K. Specific knockdown of YB1 or administration of the mTOR inhibitor rapamycin exerted a similar effect as SU056. SU056 also inhibited the co-upregulation of α-SMA and phosphorylated mTOR in liver tissue of model mice （P<0.01）. ConclusionSU056 can effectively inhibit HSC activation， proliferation， migration， and extracellular matrix production both in vivo and in vitro and thus delay the progression of liver fibrosis， by disrupting the YB1/mTOR positive feedback signaling axis.

Mesenchymal stem cells (MSCs) have been widely used in the treatment of various autoimmune and inflammation-related diseases due to their potent immunomodulatory properties. Several studies have demonstrated that MSC-mediated immunomodulation is complex and bidirectional, with the in vivo microenvironment influencing the direction of this modulation. Indoleamine-2,3-dioxygenase (IDO), an immunosuppressive factor, has been identified as a key "switch" in the immunomodulatory role of MSCs. In this review, we explore how IDO functions as a critical regulator of MSC immunoregulatory plasticity. We delve into the mechanisms by which changes in IDO expression affect the function of various immune cells, summarize relevant research and clinical advances regarding the role of IDO expression in MSC-based therapies for various diseases, and discuss potential therapeutic strategies that target IDO to enhance the stability of MSC therapeutic effects. This provides a theoretical foundation for optimizing MSCs as safer and more effective clinical therapeutic agents.

Objective:This study aimed to retrospectively analyze the impact of preoperative infection with the COVID-19 on postoperative pulmonary complications of maxillofacial surgery patients.Methods:Adult patients who underwent elective surgery under general anesthesia were included in this study.The patients were classified into three groups:control group,group infected with COVID-19 4 weeks before surgery,and group infected 4-6 weeks before surgery.The outcome measure was the postoperative pulmonary complications within 30 days.Perioperative data of all patients were collected.Logistic regression analysis was per-formed to assess the effect of infection with COVID-19 on postoperative pulmonary complications.Results:267 patients were in-cluded in this study.The incidence of postoperative pulmonary complications in control group,＜4 weeks group and 4-6 weeks group were 2.22％,11.36％,6.98％respectively.Infection with COVID-19 less than 4 weeks before surgery(OR:5.64,95％CI:1.45-21.97,P=0.006)was identified as a risk factor for postoperative pulmonary complications within 30 days.However,infection with COVID-19 during the period of 4-6 weeks did not increase the occurrence of postoperative pulmonary complications.Conclusion:Infection with COVID-19 within 4 weeks before surgery increased the risk of postoperative pulmonary complications after maxillofacial surgery.

Objective:This study aimed to retrospectively analyze the impact of preoperative infection with the COVID-19 on postoperative pulmonary complications of maxillofacial surgery patients.Methods:Adult patients who underwent elective surgery under general anesthesia were included in this study.The patients were classified into three groups:control group,group infected with COVID-19 4 weeks before surgery,and group infected 4-6 weeks before surgery.The outcome measure was the postoperative pulmonary complications within 30 days.Perioperative data of all patients were collected.Logistic regression analysis was per-formed to assess the effect of infection with COVID-19 on postoperative pulmonary complications.Results:267 patients were in-cluded in this study.The incidence of postoperative pulmonary complications in control group,＜4 weeks group and 4-6 weeks group were 2.22％,11.36％,6.98％respectively.Infection with COVID-19 less than 4 weeks before surgery(OR:5.64,95％CI:1.45-21.97,P=0.006)was identified as a risk factor for postoperative pulmonary complications within 30 days.However,infection with COVID-19 during the period of 4-6 weeks did not increase the occurrence of postoperative pulmonary complications.Conclusion:Infection with COVID-19 within 4 weeks before surgery increased the risk of postoperative pulmonary complications after maxillofacial surgery.

Objective:To summarize the best evidence for non-pharmacological management of postoperative delirium in adult liver transplant recipients, providing reference for postoperative delirium management in liver transplant recipients.Methods:Evidence on non-pharmacological management of postoperative delirium in adult liver transplant recipients was retrieved through computer in databases such as UpToDate, British Medical Journal (BMJ) Best Practice, Embase, PubMed, Cochrane Library, Joanna Briggs Institute Evidence-Based Health Care Center Database, Guidelines International Network, China Biology Medicine disc, China National Knowledge Infrastructure, WanFang Data, and VIP. The search period was from database establishment to January 31, 2023. The types of literature included guidelines, clinical decision-making, best practices, systematic review, summary of evidence, and expert consensus. Two researchers conducted quality evaluation and evidence extraction on the included literature.Results:A total of 10 articles were included, involving 1 clinical decision-making, 4 guidelines, 3 systematic reviews, and 2 expert consensuses. A total of 25 best pieces of evidence for non-pharmacological management of postoperative delirium in adult liver transplant recipients were summarized from four aspects, including screening, evaluation, non-pharmacological prevention, and non-pharmacological treatment.Conclusions:The best evidence on non-pharmacological management of postoperative delirium in adult liver transplant recipients summarized provides a reference for postoperative delirium management in liver transplant recipients.

Objective To explore the influence of continuous thermal exposure on human cognitive performance.It provides solutions for the reduction of cognitive performance caused by high temperature emergency,and reduces the misoperation problems or even safety accidents of astronauts in high temperature emergency.Methods 14 right-handed male subjects were recruited and continuously exposed to four thermal environments of 32℃,35℃,38℃,and 41℃for 150 minutes,during which 5 different cognitive tasks(Posner Cueing Task,Deary-liewald Task,N-back Task,Wisconsin Card Task,Visual Search Task)were continuously performed to obtain relative cognitive performance.At the same time,a portable 2-lead holter was used to continuously capture ECG R signals during the cognitive test.Thereafter,the heart rate variability(HRV)analysis was conducted based on the ECG data,to explore the correlations between nonlinear indices(SD1,Shannon entropy,α2,D2)and the cognitive performance.Results Tresults showed that all nonlinear indexes changed with the exposure time and exposure temperature with certain patterns.In addition,through the correlation analysis between relative cognitive performance and nonlinear indicators,the most relevant indicator is α2(correlation coefficient 0.7).The correlation analysis results showed that the nonlinear index α2 had a U-shaped relationship with relative cognitive performance(correlation coefficient was 0.7).Based on that,a quantitative relationship between α2 and relative cognitive performance was obtained.It is found that when α2 was equal to 0.98,the worst relative cognitive performance was observed.Conclusion This study showed that the HRV nonlinear index α2 could serve as a reliable indicator of the cognitive performance of human during hot exposure,which provided a potential solution for the productivity and health evaluation of astronauts.

The oral and maxillofacial region comprises a variety of organs made up of multiple soft and hard tissue, which are anatomically vulnerable to the pathogenic factors of trauma, inflammation, and cancer. The studies of this intricate entity have been long-termly challenged by a lack of versatile preclinical models. Recently, the advancements in the organoid industry have provided novel strategies to break through this dilemma. Here, we summarize the existing biological and engineering approaches that were employed to generate oral and maxillofacial organoids. Then, we detail the use of modified co-culture methods, such as cell cluster co-inoculation and air-liquid interface culture technology to reconstitute the vascular network and immune microenvironment in assembled organoids. We further retrospect the existing oral and maxillofacial assembled organoids and their potential to recapitulate the homeostasis in parental tissues such as tooth, salivary gland, and mucosa. Finally, we discuss how the next-generation organoids may benefit to regenerative and precision medicine for treatment of oral-maxillofacial illness.
Organoids ; Humans ; Tissue Engineering/methods* ; Coculture Techniques ; Regenerative Medicine ; Mouth

The oral and maxillofacial region comprises a variety of organs made up of multiple soft and hard tissue,which are anatomically vulnerable to the pathogenic factors of trauma,inflammation,and cancer.The studies of this intricate entity have been long-termly challenged by a lack of versatile preclinical models.Recently,the advancements in the organoid industry have provided novel strategies to break through this dilemma.Here,we summarize the existing biological and engineering approaches that were employed to generate oral and maxillofacial organoids.Then,we detail the use of modified co-culture methods,such as cell cluster co-inoculation and air-liquid interface culture technology to reconstitute the vascular network and immune microenvironment in assembled organoids.We further retrospect the existing oral and maxillofacial assembled organoids and their potential to recapitulate the homeostasis in parental tissues such as tooth,salivary gland,and mucosa.Finally,we discuss how the next-generation organoids may benefit to regenerative and precision medicine for treatment of oral-maxillofacial illness.

Objective:To study the genetic variation and distribution characteristics of thalassemia in people of childbearing age in Hubei Province, and to provide clinical basis for the local government decision-making departments to formulate and promote appropriate policies for prevention and control of thalassemia.Methods:Venous blood samples were collected from 44 849 people of childbearing age in hospitals in Hubei Province from May 13, 2019 to August 17, 2021. PCR-flow fluorescence hybridization and PCR+diversion hybridization were used to screen thalassemia genes. Spouses of those who tested positive were also tested for thalassemia genes. When both spouses carried the same type of thalassemia gene, the amniotic fluid of pregnant women was extracted for prenatal diagnosis and followed up.Results:Among the 44 849 people of childbearing age, 2 286 cases were diagnosed as thalassemia gene carriers through genetic testing, and the total detection rate was 5.10% (2 286/44 849). Among them, 1 488 cases were diagnosed as α-thalassemia, and the detection rate was 3.32% (1 488/44 849); 767 cases were diagnosed as β-thalassemia, and the detection rate was 1.71% (767/44 849); 31 cases were diagnosed as α-thalassemia combined with β-thalassemia, and the detection rate was 0.07% (31/44 849). The top three genotypes of α-thalassemia were -α 3.7/αα, -- SEA/αα, and -α 4.2/αα, accounting for 58.06% (864/1 488), 26.14% (389/1 488), and8.74% (130/1 488), respectively. The top three genotypes of β-thalassemia were β IVS-Ⅱ-654/β N, β CD41-42/β N, and β CD17/β N, accounting for 41.72% (320/767), 21.25% (163/767), and 16.04% (123/767), respectively. The main genotypes of α-thalassemia combined with β-thalassemia were -α 3.7/αα complex β IVS-Ⅱ-654/β N and -α 3.7/αα complex β CD41-42/β N, accounting for 29.03% (9/31) and 16.13% (5/31), respectively. A total of 59 people of childbearing age were conducted prenatal diagnosis, among fetus, there were 4 cases of severe thalassemia (2 cases of severe α-thalassemia, 2 cases of severe β-thalassemia), 5 cases of intermediate α-thalassemia, 5 cases of intermediate or severe β-thalassemia, 19 cases of mild thalassemia (8 cases of mild α-thalassemia, 11 cases of mild β-thalassemia), 13 cases of stationary α-thalassemia, and 1 case of stationary α-thalassemia combined with mild β-thalassemia, there were 12 cases without α-thalassemia or β-thalassemia genes. After follow-up, 4 cases of severe thalassemia, 2 cases of intermediate α-thalassemia, and 5 cases of intermediate or severe β-thalassemia were terminated pregnancy by the joint decision of both parents. Conclusions:In Hubei Province, the detection rate of thalassemia is high, and α-thalassemia is the main mutation type. The combination of thalassemia gene screening and prenatal diagnosis is of great significance in reducing the birth rate of children with thalassemia.