Temporomandibular disorders (TMD) are a heterogeneous group of diseases that affect the temporomandibular joint, chewing muscle system, dental occlusion, and even various structures throughout the body, with significant characteristics of biological-psychological-social pattern. TMD related chronic pain, as the most important clinical symptom, can result in negative emotions seriously affecting patients′ quality of life and physical and mental health. Although a variety of therapies have been previously reported to treat TMD related chronic pain, there is a lack of widely recognized therapies. Professor Jason W Busse (from Michael G DeGroote National Pain Centre, McMaster University, Hamilton ON, Canada) took the lead and collaborated with multiple internationally renowned schools/hospitals of stomatology to develop an international consensus on the management of chronic pain associated with TMD, a clinical practice guideline, which took two years and was published in December 15th, 2023 in a global top journal of clinical research The British Medical Journal. This clinical practice guideline explored the comparative effectiveness of available therapies for chronic pain associated with TMD, conditionally recommended the specific intervention for different treatment or pain relief, proposed a comprehensive, agreed, and standardized clinical practice guideline. This present article describes the methodology and key elements of the clinical practice guideline to help clinicians fully understand and appropriately apply this guidance, which could provide the references for clinical practice of TMD associated chronic pain in China.

BACKGROUND:The biological behavior of mesenchymal stem cells is influenced by the survival microenvironment.Pre-treatment of the microenvironment is an important means of regulating the function of mesenchymal stem cells. OBJECTIVE:To compare the differences in paracrine function of umbilical cord mesenchymal stem cells and adipose mesenchymal stem cells under oxidative stress and hypoxia,and to provide a theoretical basis for selecting appropriate pretreatment of mesenchymal stem cells to treat different diseases. METHODS:Umbilical cord mesenchymal stem cells and adipose mesenchymal stem cells were cultured by H2O2 or O2 oxygen,respectively,and cell morphology,proliferation,viability and paracrine factor expression were examined. RESULTS AND CONCLUSION:(1)The expression levels of brain-derived neurotrophic factor and transforming growth factor-β were higher in umbilical cord mesenchymal stem cells than in adipose mesenchymal stem cells under a normal culture environment,while the expressions of stromal cell-derived factor-1α and tumor necrosis factor stimulating factor-6 in the adipose mesenchymal stem cells were significantly higher than those in the umbilical cord mesenchymal stem cells.(2)There was no significant difference in the effect of low and moderate levels(≤100 μmol/L)of H2O2 on the viability of the two mesenchymal stem cells.However,increasing the H2O2 concentration from 50 μmol/L to 100 μmol/L resulted in a distinct increase in vascular endothelial growth factor expression in umbilical cord mesenchymal stem cells.The expression of basic fibroblast growth factor,vascular endothelial growth factor,stromal cell-derived factor-1α and interleukin-10 in adipose mesenchymal stem cells was greatly increased by increasing H2O2 concentration in this range.(3)1%O2 hypoxia promoted mesenchymal stem cell proliferation.After 24 hours of culture in 1%O2,gene expression levels were elevated in both mesenchymal stem cells,but the expression levels of vascular endothelial growth factor,interleukin-10 and tumor necrosis factor stimulating factor-6 were significantly higher in adipose mesenchymal stem cells than in umbilical cord mesenchymal stem cells.(4)It is concluded that hypoxia and oxidative stress preconditioning enhances the paracrine function of mesenchymal stem cells.However,mesenchymal stem cells respond differently to hypoxia and oxidative stress.Treating diseases can choose suitable mesenchymal stem cells for appropriate pretreatment to further enhance their therapeutic potential.

Objective:To study the correlation between smoking and clinicopathology in patients with upper tract urothelial carcinoma(UTUC), and to evaluate the effect of smoking on the prognosis of patients with UTUC treated with adjuvant chemotherapy for Gemcitabine plus Cisplatin (GC).Methods:A retrospective cohort study was used to select 91 patients who underwent resection of the kidney and ureter, and sleeve cystectomy in Beijing Friendship Hospital, Capital Medical University from January 2013 to December 2021, all patient received GC adjuvant chemotherapy after surgery. Patients were divided into smoking group ( n=33) and non-smoking group ( n=58) according to their smoking history. The median follow-up time was 38 months (3-83 months). The age, gender, presence or absence of hydronephrosis, tumor stage, multifocality, lymphatic vascular invasion, lymphatic metastasis, tumor grade, overall survival (OS) and cancer-specific survival (CSS) were statistically analyzed. The measurement data were expressed as mean ± standard deviation ( ± s), and the t-test was used for comparison between groups; the count data were expressed as the number of cases and percentage, and the Chi-square test was used for comparison between groups. Kaplan-Meier curve was used for survival analysis and comparison, and Long-rank test was used for comparison between groups. Cox proportional risk regression model was introduced to explore the independent influencing factors of OS and CSS by univariate and multivariate Cox regression analysis. Results:Among 91 patients, 41 were males and 50 were females, with a median age of 65 years, and 19 patients (20.9%) died, of which 17 patients (18.7%) died of UTUC. The comparison of clinical indicators between the two groups showed that smoking was associated with male, tumor stage, multifocality, lymphatic vascular invasion, lymphaitc metastasis, and tumor grade and hydronephrosis ( P<0.05). Multivariate Cox regression analysis showed that smoking, male, higher tumor stage, and lymphatic vascular invasion were independent risk factors for OS and CSS. For the subgroup of patients who smoked, smoking duration significantly affected CSS, with each additional year of smoking duration increasing the risk of death by 0.065. Conclusion:Smoking is associated with adverse pathology in patients with UTUC, and smoking is an independent factor affecting the prognosis of postoperative adjuvant chemotherapy with GC in UTUC.

Objective:To summarize the concept, theoretical basis, evaluation tools and mechanisms, influencing factors, and intervention measures of kinesiophobia.Methods:The literature on kinesiophobia in patients undergoing total knee replacement was electronically searched on databases such as China National Knowledge Infrastructure, China Biology Medicine disc, WanFang Data, PubMed, CINAHL, Web of Science, Embase, Scopus, PsycINFO, Cochrane Library. The search period was from database establishment to June 24, 2023. This study extracted and analyzed data from the included literature.Results:A total of 32 articles were included. The Tampa Scale for Kinesiophobia was a widely used tool for evaluating kinesiophobia. The influencing factors of kinesiophobia were demographic and disease factors, body motor function, and psychological and social factors. The intervention measures for kinesiophobia mainly included cognitive behavioral intervention, pain health education, exercise, art video or music intervention, multidisciplinary collaborative intervention, and so on.Conclusions:The concept and theoretical basis of kinesiophobia are not yet complete. It is necessary to revise and improve the theoretical model and assessment tool for kinesiophobia and construct an intervention program for kinesiophobia in combination with the concept of rapid rehabilitation.

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.

Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.

Tacrolimus (FK506) is a 23-membered macrolide with immunosuppressant activity that is widely used clinically for treating the rejection after organ transplantation. The research on tacrolimus production was mainly focused on biosynthesis methods, within which there are still some bottlenecks. This review summarizes the progress made in tacrolimus biosynthesis via modification of metabolic pathways and control of fermentation process, with the hope to address the technical bottlenecks for tacrolimus biosynthesis and improve tacrolimus production by fermentation engineering and metabolic engineering.
Tacrolimus ; Immunosuppressive Agents ; Fermentation ; Macrolides ; Anti-Bacterial Agents

Objective:To explore the factors influencing complete remission in patients with diffuse large B-cell lymphoma (DLBCL), and to explore the effect of the interaction of Karnofsky performance status scale (KPS) scores and the level of lactate dehydrogenases (LDH) on whether patients with DLBCL are completely relieved.Methods:The clinical data of 373 DLBCL patients admitted to Shanxi Province Cancer Hospital from January 2014 to December 2020 were retrospectively analyzed. SPSS 25.0 logistic regression model and Cox proportional risk regression models were used to explore the factors affecting complete remission in patients with DLBCL and to explore whether there was a multiplicative interaction between the factors. For factors with multiplicative interactions, the Matrix package, epiR package, and survival package in R 4.2.0 software were used to analyze whether there was an additive interaction. The relative excess risk of interaction (RERI), attributable proportion due to interaction (AP), and the synergy index (S) were used to evaluate the presence of additive interactions.Results:Elevated β 2 macroglobulin (β 2-MG), KPS scores below 80, and elevated LDH were risk factors for incomplete remission in patients with DLBCL (all P < 0.05). The risk of incomplete remission in patients with elevated β 2-MG, KPS scores below 80 and LDH was 1.971 times ( OR = 1.971, 95% CI 1.161-3.346), 2.056 times ( OR = 2.056, 95% CI 1.057-4.000) and 3.351 times ( OR = 3.351, 95% CI 1.783-6.300) higher than those in patients with normal β 2-MG, KPS scores above 80 and non-elevated LDH, respectively. There was a negative multiplicative interaction between the two risk factors of KPS scores below 80 and elevated LDH ( OR = 0.317, 95% CI 0.126-0.785). The estimated value of RERI, AP and S was -2.07 (95% CI -4.79-0.64),0.50 (95% CI -1.68-0.32),0.50 (95% CI 0.22-1.13), respectively; and there was no additive interaction among them. Conclusions:Elevated β 2-MG, KPS scores below 80, and elevated LDH are risk factors influencing incomplete remission for patients with DLBCL. The combined effect in patients with the combination of elevated LDH and KPS scores below 80 is lower than the single effect of the multiple of the both. There is a negative multiplicative interaction and no additive interaction in DLBCL patients with KPS scores below 80 and elevated LDH level.

Objective:To measure the predictive value of miR-424 on the risk of sepsis complicated with acute respiratory distress syndrome(ARDS), and to explore its correlation with the prognosis of ARDS children.Methods:A prospective study was conducted.The data of children with sepsis (some complicated with ARDS), who were treated in Henan Provincial People′s Hospital (People′s Hospital, Zhengzhou University) were collected from February 2020 to February 2021.The incidence of ARDS and the fatality rate of ARDS children were recorded.Children were divided into survival group and death group according to whether death or not.The expression of miR-424 in peripheral blood mononuclear cells was detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Pearson correlation analysis was made to investigate the relationship between the expression level of miR-424 and Pediatric Critical Illness Score(PCIS), Sequential Organ Failure Assessment(SOFA) score, oxygenation index(P/F ratio), C-reactive protein(CRP), procalcitonin (PCT), interleukin 6 (IL-6) and interleukin 8 (IL-8). The factors affecting the prognosis of ARDS children were analyzed by multivariate Logistic regression.Receiver operating characteristic curve(ROC)was used to assess the accuracy of miR-424 in early diagnosis of sepsis complicated with ARDS, and to measure the predicative value of miR-424 on the risk of death in sepsis patients with ARDS. Results:A total of 121 sepsis patients were included in this study, and 36 cases of them were complicated with ARDS.The expression level of miR-424(0.56±0.17)in the blood of sepsis patients complicated with ARDS was significantly lower than that of sepsis patients without ARDS (0.98±0.26)( t=8.776, P<0.001). The expression of miR-424 was negatively co-rrelated with IL-6( r=-0.627, P<0.01), IL-8 ( r=-0.651, P<0.01) and CRP( r=-0.472, P<0.05)in sepsis patients with ARDS.The expression of miR-424 was positively correlated with PCIS score( r=0.330, P<0.05), P/F ratio ( r=0.592, P<0.001) and albumin ( r=0.496, P<0.05) in sepsis patients with ARDS.The ROC showed that miR-424 [area under curve(AUC)=0.908, 95% CI: 0.856-0.960] could differentiate sepsis patients with ARDS from those without ARDS.Compared with that of the survival group(0.63±0.15), miR-424 of the death group decreased significantly(0.42±0.14)( t=3.890, P<0.05). The decreased miR-424 (AUC=0.845, 95% CI: 0.696-0.995)indicated an increased risk of death in children with ARDS.Multivariate Logistic regression analysis showed that miR-424( OR=0.001, P=0.033)and albumin ( OR=0.553, P=0.040) were independent risk factors for death in ARDS children. Conclusions:miR-424 can help with early diagnosis of sepsis complicated with ARDS, and can be used as a predictor of the prognosis of sepsis children complicated with ARDS.

Objective:To study the epidemiological characteristics and spatio-temporal aggregation of hemorrhagic fever with renal syndrome (HFRS) in Shandong Province, and to provide reference for formulating reasonable prevention and control strategies.Methods:Retrospective analysis was used to collect HFRS surveillance data and confirmed case data in Shandong Province from 2017 to 2020 in the "China Disease Prevention and Control Information System Infectious Disease Surveillance System". Geoda 1.18 software was used for global and local spatial autocorrelation analysis, SaTScan 9.6 software was used for spatio-temporal scanning analysis, and ArcGis 10.7 software was used for map drawing and visual display.Results:A total of 3 753 cases of HFRS were reported in Shandong Province from 2017 to 2020, including 56 deaths. The annual incidence rate was 1.26/100 000, 1.22/100 000, 0.75/100 000 and 0.53/100 000, respectively, with an average annual incidence rate of 0.94/100 000. The incidence of HFRS was obviously seasonal, mainly concentrated in autumn and winter from October to December, accounting for 50.41% (1 892/3 753). The age of onset was mainly 30-59 years old, accounting for 61.68% (2 315/3 753). The male to female ratio was 2.76 ∶ 1.00 (2 756 ∶ 997). The occupation distribution was mainly farmers, accounting for 81.99% (3 077/3 753). The global spatial autocorrelation analysis showed that HFRS showed spatial aggregation areas in each year from 2017 to 2020 (Moran' I = 0.38, 0.33, 0.59, 0.46, Z = 7.47, 7.23, 10.69, 8.66, P < 0.001). The local spatial autocorrelation analysis showed that "high-high" aggregation areas were mainly concentrated in central and southeast of Shandong Province, while "low-low" aggregation areas were mainly concentrated in northwest of Shandong Province. Spatio-temporal scanning analysis revealed 1 type Ⅰ agglomerations and 2 type Ⅱ aggregation areas. The type Ⅰ aggregation areas occurred from October to November 2018, covering 22 counties (districts) of 5 cities in Qingdao, Yantai, Weifang, Weihai and Rizhao. The first type Ⅱ aggregation area occurred from October to November 2017, involving 23 counties (districts) of 8 cities in Jinan, Zibo, Zaozhuang, Weifang, Jining, Tai 'an, Rizhao and Linyi. The second type Ⅱ aggregation area occurred in Jinxiang County, Jining City from February to March 2017. Conclusion:The incidence of HFRS in Shandong Province from 2017 to 2020 has obvious spatio-temporal aggregation, and the hot spots are concentrated in central and southeast of Shandong Province, which should be regarded as a key area for prevention and control of HFRS.