Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment.However,irrigant selection or irrigation procedures are far from clear.The vapor lock effect in the apical region has yet to be solved,impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.Additionally,ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified.Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes.Indeed,clinicians have been aware of these concerns for years.Based on the current evidence of studies,this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions.The evolution of different kinetic irrigation methods,their effects,limitations,the paradigm shift,current indications,and effective operational procedures regarding intracanal medication are also discussed.This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication,thus facilitating a better understanding of infection control,standardizing clinical practice,and ultimately improving the success of endodontic therapy.

Objective: To evaluate the secondary attack rates of the SARS-CoV-2 Omicron variant and the associated factors. Methods: A total of 328 primary cases and 40 146 close contacts of the SARS-CoV-2 Omicron variant routinely detected in local areas of Jiangsu Province from February to April 2022 were selected in this study, and those with positive nucleic acid test results during 7 days of centralized isolation medical observation were defined as secondary cases. The demographic information and clinical characteristics were collected, and the secondary attack rate (SAR) and the associated factors were analyzed by using a multivariate logistic regression model. Results: A total of 1 285 secondary cases of close contacts were reported from 328 primary cases, with a SAR of 3.2% (95%CI: 3.0%-3.4%). Among the 328 primary cases, males accounted for 61.9% (203 cases), with the median age (Q₁, Q₃) of 38.5 (27, 51) years old. Among the 1 285 secondary cases, males accounted for 59.1% (759 cases), with the median age (Q₁, Q₃) of 34 (17, 52) years old. The multivariate logistic regression model showed that the higher SAR was observed in the primary male cases (OR=1.632, 95%CI: 1.418-1.877), younger than 20 years old (OR=1.766, 95%CI: 1.506-2.072),≥60 years old (OR=1.869, 95%CI: 1.476-2.365), infected with the BA.2 strain branch (OR=2.906, 95%CI: 2.388-3.537), the confirmed common cases (OR=2.572, 95%CI: 2.036-3.249), and confirmed mild cases (OR=1.717, 95%CI: 1.486-1.985). Meanwhile, the higher SAR was observed in the close contacts younger than 20 years old (OR=2.604, 95%CI: 2.250-3.015),≥60 years old (OR=1.287, 95%CI: 1.052-1.573) and exposure for co-residence (OR=27.854, 95%CI: 23.470-33.057). Conclusion: The sex and age of the primary case of the Omicron variant, the branch of the infected strain, case severity of the primary case, as well as the age and contact mode of close contacts are the associated factors of SAR.
Humans ; Male ; Middle Aged ; Young Adult ; Adult ; COVID-19/epidemiology* ; Incidence ; SARS-CoV-2 ; Logistic Models

Humans ; Diverticulum, Colon/surgery* ; Cholecystectomy/adverse effects* ; Tomography, X-Ray Computed

Objective: To evaluate the secondary attack rates of the SARS-CoV-2 Omicron variant and the associated factors. Methods: A total of 328 primary cases and 40 146 close contacts of the SARS-CoV-2 Omicron variant routinely detected in local areas of Jiangsu Province from February to April 2022 were selected in this study, and those with positive nucleic acid test results during 7 days of centralized isolation medical observation were defined as secondary cases. The demographic information and clinical characteristics were collected, and the secondary attack rate (SAR) and the associated factors were analyzed by using a multivariate logistic regression model. Results: A total of 1 285 secondary cases of close contacts were reported from 328 primary cases, with a SAR of 3.2% (95%CI: 3.0%-3.4%). Among the 328 primary cases, males accounted for 61.9% (203 cases), with the median age (Q₁, Q₃) of 38.5 (27, 51) years old. Among the 1 285 secondary cases, males accounted for 59.1% (759 cases), with the median age (Q₁, Q₃) of 34 (17, 52) years old. The multivariate logistic regression model showed that the higher SAR was observed in the primary male cases (OR=1.632, 95%CI: 1.418-1.877), younger than 20 years old (OR=1.766, 95%CI: 1.506-2.072),≥60 years old (OR=1.869, 95%CI: 1.476-2.365), infected with the BA.2 strain branch (OR=2.906, 95%CI: 2.388-3.537), the confirmed common cases (OR=2.572, 95%CI: 2.036-3.249), and confirmed mild cases (OR=1.717, 95%CI: 1.486-1.985). Meanwhile, the higher SAR was observed in the close contacts younger than 20 years old (OR=2.604, 95%CI: 2.250-3.015),≥60 years old (OR=1.287, 95%CI: 1.052-1.573) and exposure for co-residence (OR=27.854, 95%CI: 23.470-33.057). Conclusion: The sex and age of the primary case of the Omicron variant, the branch of the infected strain, case severity of the primary case, as well as the age and contact mode of close contacts are the associated factors of SAR.
Humans ; Male ; Middle Aged ; Young Adult ; Adult ; COVID-19/epidemiology* ; Incidence ; SARS-CoV-2 ; Logistic Models

The blood-brain barrier(BBB), a protective barrier between brain tissues and brain capillaries, can prevent drugs from entering the brain tissues to exert the effect, which greatly increases the difficulty in treating brain diseases. The drug delivery system across the BBB can allow efficient drug delivery across the BBB by virtue of carriers and formulations, thereby enhancing the therapeutic effect of drugs on brain tissue diseases. Liposomes and micelles have been extensively studied with advances in the targeted therapy across the BBB for the brain due to their unique structures and drug delivery advantages. This study summarized the research status of liposome and micelle drug delivery systems across the BBB based on the literature in recent years and analyzed their application advantages and mechanism in terms of trans-BBB capability, targeting, and safety. Moreover, the problems and possible countermeasures in the research on trans-BBB liposomes and micelles were discussed according to the current clinical translation, which may provide refe-rences and ideas for the development of trans-BBB targeted nano-drugs.
Humans ; Blood-Brain Barrier ; Liposomes ; Micelles ; Drug Delivery Systems ; Biological Transport ; Brain ; Brain Diseases

Tibetan medicine is an essential part of Chinese medicine and has unique theoretical experience and therapeutic advantages. According to the development principle of inheriting the essence, sticking to the truth, and keeping innovative, the supervision department should give clear and reasonable guidance considering the characteristics of Tibetan medicine, establish a standard system for quality control, clinical verification and evaluation, and accelerate the research and commercialization of new drugs. In view of the needs of drug supply-side reform and the current situation of Tibetan medicine and new pharmaceutical research, we ponder and provide suggestions on the confusion faced by the current supervision of Tibetan drug registration, hoping to contribute to the supervision strategy of Tibetan drug registration and the high-quality development of Tibetan medicine industry.
Tibet ; Medicine, Tibetan Traditional ; Quality Control ; Pharmaceutical Research ; Drug Industry

OBJECTIVE: To investigate the effect and mechanism of artesunate (ARTS) combined with cytarabine(Ara-C) and/or daunorubicin (DNR) on the proliferation and apoptosis of MV4-11 human mixed-lineage leukemia rearranged（MLL-r） acute myeloid leukemia (AML) cell line. METHODS: CCK-8 assay was used to detect the proliferation effect of individual or in combination of ARTS, DNR, Ara-C on MV4-11 cells. The IC₅₀ of ARTS, DNR and Ara-C was calculated separately. The cell apoptosis and expression of receptors DR4 and DR5 were detected by flow cytometry. Western blot was used to detect the expression of Caspase-3 and Caspase-9 in each groups. RESULTS: The inhibition effect of ARTS, Ara-C and DNR on the proliferation of MV4-11 were all dose-dependently (r=0.99, 0.90 and 0.97, respectively). The IC₅₀ of ARTS, Ara-C and DNR on MV4-11 for 48 hours were 0.31 μg/ml, 1.43 μmol/L and 22.47 nmol/L, respectively. At the dose of ARTS 0.3 μg/ml， Ara-C 1.0 μmol/L and DNR 15 nmol/L, the proliferation rate for 48 hours of the tri-combination treatment was significantly lower than that of the bi-combination treatment, while both were significantly lower than that of the individual treatment (all P＜0.05). In terms of bi-combination treatment, the cells proliferation rate for 48 hours of the ARTS+Ara-C group was significantly lower than that of the ARTS+DNR group, while both were significantly lower than that of the Ara-C+DNR group (all P＜0.05). The cooperativity index (CI) of bi- and tri-combination treatment were all less than 1. After 48 hours of drug action, the cell apoptosis rate of the ARTS+DNR+Ara-C group was significantly higher than that of the Ara-C+DNR group, while both were significantly higher than that of the ARTS+DNR group (all P＜0.05). Meanwhile, the was no statistical difference between the cells apoptotic rate of the ARTS+DNR+Ara-C group and the ARTS+Ara-C group (P>0.05). The expression of DR4 and DR5 also showed no difference between control group and drug group. Compared with the DNR+Ara-C group, the expressions of Caspase-3 were significantly down-regulated in both the ARTS+DNR+Ara-C group and the ARTS+Ara-C group (all P＜0.05). The down-regulation of Caspase-3 expression was the most significantly in the combination group of three drugs, while the Caspase-9 expressions in different groups showed no apparent change. CONCLUSION The in vitro study showed that tri-combination of ARTS+Ara-C+DNR and bi-combination of ARTS+Ara-C could inhibit the proliferation and promote apoptosis of MV4-11 cell line. The inhibition effect of these two combinations were significantly superior to that of the traditional Ara-C+DNR treatment. The mechanism underlying this finding may be identified by the down regulation of Caspase-3, while no altered expression was observed of Caspase-9, DR4 and DR5.
Humans ; Cytarabine/pharmacology* ; Daunorubicin/pharmacology* ; Caspase 3 ; Caspase 9 ; Artesunate/pharmacology* ; Leukemia, Myeloid, Acute ; Apoptosis ; Cell Line

Objective To investigate the effects of hot spring baths on blood pressure, resting heart rate, cardiovascular function related indicators and physical signs in population with high-normal blood pressure. Methods Residents of typical hot spring areas in Guizhou Province were included as the subjects. According to the epidemiological survey of the research group and the physical examination results before the intervention, combined with the inclusion and exclusion criteria, a total of 217 people with high normal blood pressure were selected as the observation subjects. The intervention of hot spring baths was carried out for four weeks, once time per day, 5 times per week, for 40-50 minutes each time. After the intervention, the blood pressure, resting heart rate and serum levels of creatine kinase(CK), lactate dehydrogenase(LDH), and α-hydroxybutyrate dehydrogenase(α-HBDH)were detected, and the improvement of cardiovascular related signs(palpitation, dizziness/headache, cough/sputum and night sweats)were clinically examined. SPSS 23.0 software was used for statistical analysis. Results Paired t-test results showed that the systolic blood pressure, diastolic blood pressure and resting heart rate of 217 high normal blood pressure subjects were significantly lower after hot spring baths(P < 0.01). Further analysis revealed that the number of people with high normal blood pressure dropped from 217 to 128 after the hot spring baths. Before the intervention, 95 of the 217 people with high-normal blood pressure had resting heart rates between 80 and 90 beats/min, and 35 of them above 90 beats/min. After the intervention, the resting heart rates of those above people decreased to 68 and 14, respectively. Serum levels of cardiovascular related indicators showed that CK, LDH, and α-HBDH levels in people with high-normal blood pressure decreased to some extent after the intervention, and CK level was significantly lower than that before the intervention(P < 0.05). The results of clinical examination showed that hot spring baths had a significant improvement effect on palpitation, dizziness/headache, cough/expectoration, and night sweats in people with high-normal blood pressure. Conclusion The typical hot spring baths in Guizhou Province can reduce the blood pressure and resting heart rate in population with high-normal blood pressure, and improve the cardiovascular function related indicators and physical signs to a certain extent.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

ObjectiveTo investigate the effects of rotenone （ROT） on cognitive function of rats， as well as on Warburg effect and microglia polarization in the hippocampus of rats. MethodsMale Sprague Dawley （SD） rats were randomly divided into ROT-treated group and control group which were subcutaneously injected with ROT （2 mg/kg） and same volume of saline respectively. The cognitive function of rats was evaluated by Y-maze test and novel object recognition （NOR） test. Western blot （WB） was conducted to detect the expression levels of Warburg effect related proteins including hexokinase 2 （HK2）， pyruvate kinase isozyme M2 （PKM2）， pyruvate dehydrogenase kinase 1 （PDK-1）， pyruvate dehydrogenase （PDH）， and lactate dehydrogenase A （LDHA） in the hippocampus， as well as the expression levels of the microglia polarization marker proteins including inducible nitric oxide synthase （iNOS）， arginase-1 （Arg-1）， and chitinase 3-like protein 3 （Ym-1） in the hippocampus. The lactate production and concentration of nitric oxide （NO） in the hippocampus were determined by lactate assay kit and Griess method， respectively. Enzyme-linked immunosorbent assay was used to measure the levels of interleukin-1β （IL-1β）， interleukin-4 （IL-4）， and transforming growth factor β1 （TGF-β1） in the hippocampus. ResultsThe ROT-treated rats showed impaired cognitive function， presented as a significantly lower alternation rate （P < 0.05） in Y-maze test and recognition index （P < 0.001） in NOR test compared with control rats. In the hippocampus of ROT-treated rats， the expressions of HK2 （P < 0.05）， PKM2 （P < 0.01）， PDK-1 （P < 0.05） and LDHA （P < 0.05） were downregulated， The PDH expression was upregulated （P < 0.05）， and the lactate production （P < 0.05） was reduced， indicating that ROT inhibited Warburg effect in the hippocampus of rats. The hippocampus of ROT-treated rats also exhibited increased iNOS expression （P < 0.05）， NO concentration （P < 0.05）， and IL-1β level （P < 0.01）， decreased expression of Arg-1（P < 0.01） and Ym-1 （P < 0.01）， and reduced levels of IL-4 （P < 0.05） and TGF-β1 （P < 0.05）， indicating that ROT promoted M1 polarization of hippocampal microglia. ConclusionROT impairs the cognitive function of rats， inhibits the hippocampal Warburg effect and promotes M1 polarization of hippocampal microglia.