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::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

OBJECTIVE: To compare the safety of low-dose cyclophosphamide and high-dose cyclophosphamide in the treatment of systemic lupus erythematosus (SLE). METHODS: A total of 1 022 patients with systemic lupus erythematosus from 24 hospitals in China between March 2017 to July 2018 were enrolled. Their clinical manifestations, laboratory tests, adverse events, reasons for stopping receiving intravenous cyclophosphamide and comorbidities were collected. Among them, 506 SLE patients received short-interval low-dose intravenous cyclophosphamide therapy (SILD IV-CYC, 400 mg every two weeks), and 256 patients underwent high-dose cyclophosphamide therapy (HD IV-CYC, 500 mg/m² of body surface area every month), the side effects between the two groups were compared, the remaining 260 SLE patients were treated with IV-CYC irregularly. Moreover, a total of 377 patients in SILD IV-CYC group and 214 patients in HD IV-CYC group had medical records of the reasons for stopping recei-ving IV-CYC. The reasons for stopping receiving IV-CYC in these two groups were analyzed. RESULTS: In this study, only 40.27%(238/591)of the SLE patients stopped receiving intravenous cyclophosphamide for the causes of disease improvement, however, up to 33.67% (199/591) of the patients for the reason of drug-related side effects. There were 83 patients out of 214 (38.79%) with high-dose intravenous cyclophosphamide treatment who stopped receiving IV-CYC for the drug-related side effects, which was significantly higher than that in the low-dose cyclophosphamide group (30.77%, 116/337, P=0.048). Of theses 506 patients in SILD IV-CYC group, 88 (17.39%) patients experienced gastrointestinal reactions, 66 (13.04%) suffered from infections, 49 (9.68%) had myelosuppression and 68 (13.44%) had alopecia, respectively. Among the 256 patients in the HD IV-CYC group, 80 (31.25%) experienced gastrointestinal reactions, 57 (22.27%) suffered from infections, 51 (19.92%) had myelosuppression and 49 (19.14%) had alopecia. Moreover, 71 (25.18%) of 282 female patients with age between 16 to 45 years in SILD IV-CYC group had abnormal menstruation, while menstrual disorder occurred in 39.72% (56/141) patients of HD IV-CYC group. There was no difference of drug-induced hepatic injury, hemorrhagic cystitis and fatigue between the two groups. CONCLUSION Low-dose cyclophosphamide showed a lower prevalence of adverse events than high-dose cyclophosphamide in systemic lupus erythematosus patients.
Humans ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Immunosuppressive Agents/adverse effects* ; Cyclophosphamide/therapeutic use* ; Lupus Erythematosus, Systemic/drug therapy* ; Administration, Intravenous ; Alopecia/drug therapy*

Measurement of corpse temperature is mainly used for estimation of early postmortem interval, and rectal temperature is often used as a representative of body's core temperature in actual work because it is simple, quick and non-invasive. At present, the rectal temperature postmortem interval estimation method internationally accepted and widely used is HENSSGE's nomogram method, while many domestic scholars also deduced their own regression equations through a large number of case data. Estimation of postmortem interval based on rectal temperature still needs further study. The nomogram method needs to be optimized and extended, and quantification of its influencing factors needs to be dealt with more scientifically. There is still a lack of consensus on the probability and duration of the temperature plateau. There is no clear understanding of the probability and extent of the change in initial temperature caused by various causes. New methods and ideas enrich methodological research, but it still lacks systemicity and practicality. This article reviews the researches on estimation of postmortem interval based on rectal temperature in order to summarize the current situation of previous researches and seek new breakthrough points. Because the decline of body temperature can be easily influenced by many factors in vitro and vivo, and the influencing factors in different regions vary greatly, regionalization research and application may be a practical exploration to improve the accuracy of postmortem interval determination.
Autopsy ; Body Temperature ; Cadaver ; Humans ; Postmortem Changes ; Probability ; Temperature ; Time Factors

Objects To explore the association of ulcerative colitis (UC) with the imbalance between Th1,Th 2 and Th17 cells in the colonic tissues.Methods A total of 41 UC patients and 52 controls was recruited in the present study.The real-time fluorescent quantitative PCR was applied for detecting the mRNA levels of Thl,Th2 and Th 17 cells-associated transcription factors T-bet,GATA-3 and RORγt and cytokines IFN-γ,IL-4 and IL-17A in the colonic tissues.Simultaneously,the expressions of IFN-γ,IL-4 and IL-17A in the colonic tissues were also examined by an immunohistochemical staining method.Results Compared with the controls,the mRNA expressions of GATA-3,RORγt and IL-17A were more significantly enhanced in UC patients (0.84 ± 0.24 vs.0.69 ± 0.22,P=0.002;0.99 ± 0.29 vs.0.83 ± 0.23,P=0.004;1.59 ± 0.65 vs.1.35 ± 0.43,P=0.035).According to the ＂Truelove and Witts Severity Index＂,those patients were divided into different subgroups.The mRNA expressions of GATA-3,RORγt,and IL-17A were shown to be higher in patients with moderate and severe UC than in those with mild UC (0.90 ± 0.18 vs.0.78 ± 0.16,P=0.030;1.11 ± 0.31 vs.0.87 ± 0.26,P=0.011;1.83 ± 0.64 vs.1.34 ± 0.66,P=0.020).Moreover,the immunohistochemistry results demonstrated that the IL-17A positive cells were positioned mainly in the intestinal epithelial layer and lamina propria.Compared to the controls,the mean integral optic density of IL-17A was significantly increased in the colonic tissues of UC patients (0.25 ± 0.07 vs.0.13 ± 0.03,P＜0.001).The similar results were obtained for IL-17A in patients with moderate and severe UC when compared to those with mild UC (0.31 ± 0.07 vs.0.19 ± 0.06,P＜0.001).In contrast to the controls,the mRNA ratios ofGATA-3/T-bet,RORγt/ T-bet and RORγt/GATA-3 were significantly higher in the tissues of colonic UC patients (1.12 ± 0.30 vs.0.96 ± 0.31,P=0.014;1.33 ± 0.37 vs.1.15 ± 0.33,P=0.015;1.44 ± 0.45 vs.1.20 ± 0.42,P=0.009),and in the patients,the mRNA ratios for GATA-3/T-bet,RORγt/T-bet and RORγt/GATA-3 were significantly higher in the patients with moderate and severe UC than in those with mild UC (1.27 ± 0.35 vs.1.00 ± 0.32,P＜0.001;1.45 ± 0.37 vs.1.19 ± 0.36,P=0.028;1.59 ± 0.43 vs.1.28 ± 0.46,P=0.031).Conclusions These findings suggest that the imbalance between Thl,Th2 and Th17 cells in the colonic tissues may be implicated in UC.

Purpose To investigate the mutation rate of EGFR,KRAS,ALK and ROS1 in non-small cell lung cancer (NSCLC) and its association with clinical or pathological characteristics.Methods 86 NSCLC tissues were included.Fluorescence PCR was used to detect the EGFR,KRAS mutation and ALK,ROS1 fusion gene.The association between EGFR,KRAS,ALK and ROS1 gene and age,gender,smoking history,histological type,lymph node metastasis and other clinical pathological features were analyzed.Results The total mutation rate of the driver gene in NSCLC patients was 62.8％ (54/86).EGFR mutation rate was 76％ (41/54).KRAS mutation rate was 9.3％ (5/54).ALK gene fusion mutation rate was 13.0％ (7/54),and in one of the patients,EGFR 19 deletion mutation and ALK fusion co-exist.ROS1 gene fusion mutation was 3.8％ (2/54).EGFR gene mutation rate was higher in adenocarcinoma and female (P ＜ 0.05),but no significant association was found in age,smoking history and lymph node metastasis (P ＞0.05).KRAS,ALK,ROS1 genes had no obvious correlation with clinical pathological features (P ＞ 0.05).Conclusion The EGFR mutation and ALK fusion was rather high in patients with NSCLC.More attention should be paid to them.Though KRAS,ROS1 mutations and double mutations were low in NSCLC patients,they should not be ignored.

Purpose To investigate the prevalence of EG-FR mutation in circulating cell-free DNA in non-small cell lung cancer (NSCLC) patients of Yunnan province and its relationship with clinical pathological characteristics,which can provide foundations for individualized targeted therapy of lung cancer in this area.Methods Amplification refractory mutation system (ARMS) was used to detect the EGFR exon 18,19,20 and 21 mutation in circulating cell-free DNA.The relationship between EGFR mutation and clinical characteristics were further analyzed.Results 93 patients (25.5％) harbored circulating EG-FR mutations among 364 patients.The mutation rates of EGFR 18 G719X,19del,20 S768I,T790M,20ins were 3.2％ (3/93),2.2％ (2/93)and3.2％ (3/93)respectively.EGFR21 L858R and L861Q mutation rates were 26.9％ (25/93) and 1.1％ (1/93),respectively.Three patients (3.2％,3/93)harbored G719X + S768I double mutation,four patients (4.3％,4/93) harbored 19Del + T790M mutations.19Del +L858R,L858R + S768I,and S768I + T790M mutation rates were 1.1％ (1/93),1.1％ (1/93) and 2.2％ (2/93) respectively.Conclusion The EGFR mutation rate of female and adenocarcinoma patients is higher in patients with stage Ⅲ B-ⅣNSCLC in Yunnan area.19Del is the major mutation type and double exon mutation is an obvious characteristic in NSCLC patients of Yunnan province.EGFR mutation detection in circulating cell-free DNA by ARMS method is feasible to screen patients receiving EGFR-TKIs treatment.

The opening of mitochondrial permeability transition pore (MPTP) plays a critical role in platelet activation. However, the potential trigger of the MPTP opening in platelet activation remains unknown. Inflammation is the crucial trigger of platelet activation. In this study, we aimed to explore whether and how the important inflammatory cytokine IL-17 is associated with MPTP opening in platelets activation by using MPTP inhibitor cyclosporine-A (CsA). The mitochondrial membrane potential (ΔΨm) was detected to reflect MPTP opening levels. And the platelet aggregation, activation, and the primary signaling pathway were also tested. The results showed that the MPTP opening levels were increased and Δψm reduced in platelets administrated with IL-17. Moreover, the levels of aggregation, CD62P, PAC-1, P53 and the phosphorylation of ERK2 were enhanced along with the MPTP opening in platelets pre-stimulated with IL-17. However, CsA attenuated these effects triggered by IL-17. It was suggested that IL-17 could induce MPTP opening through ERK2 and P53 signaling pathway in platelet activation and aggregation.
Blood Platelets ; cytology ; drug effects ; metabolism ; Cell Separation ; Cyclosporine ; pharmacology ; Dual Specificity Phosphatase 2 ; genetics ; metabolism ; Gene Expression Regulation ; Humans ; Interleukin-17 ; metabolism ; pharmacology ; Membrane Potential, Mitochondrial ; drug effects ; Mitochondria ; drug effects ; metabolism ; Mitochondrial Membrane Transport Proteins ; agonists ; antagonists & inhibitors ; genetics ; metabolism ; Mitogen-Activated Protein Kinase 1 ; genetics ; metabolism ; P-Selectin ; genetics ; metabolism ; Phosphorylation ; drug effects ; Platelet Activation ; drug effects ; Platelet Aggregation ; drug effects ; Primary Cell Culture ; Signal Transduction ; Tumor Suppressor Protein p53 ; genetics ; metabolism

Thais luteostoma has been utilized as a crude drug whose shell and soft tissue have been widely used for the treatment of heat syndrome in China for thousands of years. The present study was designed to investigate the antipyretic and anti-inflammatory activities of T. luteostoma. T. luteostoma was divided into shell (TLSH) and soft tissue (TLST) samples in the present study. The rat model of yeast-induced fever was used to investigate their antipyretic effects; and the rat model of hind paw edema induced by carrageenan was utilized to study their anti-inflammatory activities, and at the same time, the concentration variations of the central neurotransmitter [prostaglandin E2 (PGE2) and cyclic adenosine monophosphate (cAMP)], inflammatory mediators [tumor necrosis factor (TNFα), interleukin-1β (IL-1), interleukin-2 (IL-2) and interleukin-6 (IL-6)] and ion (Na(+) and Ca(2+)) were also tested. The results showed that TLSH and TLST extracts significantly inhibited yeast-induced pyrexia in rats (P < 0.05), and exhibited more lasting effects as compared to aspirin, and TLSH had the better antipyretic activity than TLST, and that TLSH and TLST could significantly prevent against carrageenan induced paw edema in rats (P < 0.05); and markedly reduced levels of PGE2, cAMP, TNFα, IL-1β, IL-2, IL-6, and Na(+)/Ca(2+). In fever model, TLST could significantly reduce the levels of PGE2 (P < 0.01) in rats' homogenate and TNFα (P < 0.05), IL-1β (P < 0.01) in the plasma than TLSH, whereas TLSH could reduce the content of IL-2 (P < 0.01) and IL-6 (P < 0.01) in plasma and increase the content of Ca(2+) (P < 0.01) in plasma and homogenate more significantly than TLST. In conclusion, T. luteostoma extract has antipyretic and anti-inflammatory activities, which may be mediated through the suppression of production of PGE2, cAMP, Na(+)/Ca(2+), TNFα, IL-1β, IL-2, and IL-6.
Animal Shells ; chemistry ; Animals ; Anti-Inflammatory Agents ; pharmacology ; Antipyretics ; pharmacology ; Carrageenan ; Complex Mixtures ; pharmacology ; Edema ; chemically induced ; drug therapy ; Fever ; chemically induced ; drug therapy ; Hindlimb ; Inflammation Mediators ; blood ; Male ; Rats ; Rats, Sprague-Dawley ; Saccharomyces cerevisiae ; Snails ; chemistry

Objective To compare the drug concentration difference of voriconazole in mice serum and lung tissue by voriconazole atomization inhalation or intravenous injection , to supply the evidence for the vori-conazole atomization inhalation.Methods Mice were given voriconazole by atomization inhalation ( treatment group ) or intravenous injection ( con-trol group.The serum and lung tissue were collected before voriconazole administration and after 30 minutes on the forth day , seventh day and tenth day , then assay the voriconazole concentration of serum and lung tissue.The liver and renal index were also assayed .Results In the treatment group , the peak concentration and the trough concentration in lung tissue were higher than the serum concentration . In the control group, the peak concentration in serum was higher.Meanwhile, the trough concentration decreased evidently .The serum concentration was higher than the lung tissue concentration .The peak concentration in lung tissue was lower in treatment group than in the control group .But the trough concentration was higer in treatment group than in the control group after 7, 10 days administration.The mice in control group had an elavatin of serum alanine transaminase after 7 days administration.Conclusion The voriconazole concentration in ser-um was low and the drug concentration in mice lung tissue last longer by voriconazole atomization inhalation .Voricon-azole atomization inhalation had less influence on the liverfunction .