Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

G protein-coupled receptors (GPCRs) are the largest family of membrane proteins in eukaryotes, with nearly 800 genes coding for these proteins. They are involved in many physiological processes, such as light perception, taste and smell, neurotransmitter, metabolism, endocrine and exocrine, cell growth and migration. Importantly, GPCRs and their ligands are the targets of approximately one third of all marketed drugs. GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane. However, emerging evidence suggests that GPCRs are also localized on mitochondria, where they play critical roles in modulating mitochondrial functions. These mitochondrial GPCRs (mGPCRs) can influence processes such as mitochondrial respiration, apoptosis, and reactive oxygen species (ROS) production. By interacting with mitochondrial signaling pathways, mGPCRs contribute to the regulation of energy metabolism and cell survival. Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling, highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction. This expanding understanding of mGPCR function on mitochondria opens new avenues for research, particularly in the context of diseases where mitochondrial dysfunction plays a key role. Abnormalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease, diabetes, obesity and Alzheimer's disease. In this review, we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases. We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease, and to underscore their potential as therapeutic targets in the treatment of these conditions.

OBJECTIVE: To compare the clinical efficacy between microscopic varicocelectomy and laparoscopic varicocelectomy in the treatment of varicocele（VC）with male infertility. METHODS: A total of 307 patients who were diagnosed with VC complicated with male infertility and admitted to the Affiliated Hospital of Qingdao University from October 2018 to October 2022 were recruited for retrospective analysis. The patients were divided into the microscopic group (180 cases) and laparoscopic group (127 cases) according to the surgery method. The pre- and postoperative clinical data of these two groups were analyzed, including the degree of dilatation and reflux time of internal spermatic vein，hemodynamic parameters of testicular capsular artery，proportion of progressive motility spermatozoa (PR), concentration of spermatozoa, proportion of normal morphology sperm，the pregnancy outcome of spouses and the incidence of complications related with surgery within 2 years postoperatively. RESULTS: All the surgeries for the 307 patients in this study were successful. There was no significant difference in operation time, hospitalization time and management expenses between the microscopic group and the laparoscopic group (P>0.05). Compared to the patients in laparoscopic group, the patients in the microscopic group received a better improvement in venous diameter, reflux time of spermatic veins and hemodynamic parameters of testicular capsular artery (P<0.05). Moreover, the semen analysis showed that the PR, spermatozoa concentration and proportion of normal morphology sperm in the microscopic group were also obviously increased than those in the laparoscopic group (P<0.05). During the 2-year follow-up period, the conception rate of spouses in the microscopic group was 67.2%, while only 47.2% in the laparoscopic group, in which the difference was statistically significant (P<0.05). Besides, the time-to-pregnancy ( TTP ) within 2 years postoperatively in the microscopic group was significantly shorter than that in the laparoscopic group（P<0.05). Meanwhile, the incidence of adverse pregnancy outcomes in the microscopic group was also significantly lower than that in the laparoscopic group (P<0.05). It is worth mentioned that the spontaneous conception rate of spouses with successful pregnancy in the microscopic group was also significantly higher than that in the laparoscopic group (P<0.05). Severe complication such as testicular atrophy, bleeding and infection did not appear in both of two groups. However, the incidences of testicular hydrocele and recurrence of VC postoperatively in the laparoscopic group were significantly higher than those in the microscopic group (P<0.05). CONCLUSION Both microscopic varicocelectomy and laparoscopic varicocelectomy can be applied to the management of VC combined with male infertility. But microscopic varicocelectomy showed better clinical efficacy in improving the testicular hemodynamic parameters, semen quality, pregnancy outcome and postoperative complications, which is worthy of further clinical applications.
Humans ; Male ; Varicocele/complications* ; Laparoscopy ; Infertility, Male/etiology* ; Retrospective Studies ; Adult ; Microsurgery ; Treatment Outcome ; Pregnancy ; Female

BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.

Objective To explore the clinical value of high-frequency ultrasound-guided labial gland biopsy in patients with suspected Sj?gren's syndrome(SS).Methods Totally 126 patients with clinically suspected SS and salivary gland involvement who underwent labial gland biopsy in Department of Ultrasound and Department of Rheumatology and Immunology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from Sep.2022 to Dec.2024 were enrolled.The patients who underwent traditional excision labial gland biopsy from Sep.2022 to Feb.2023 were selected as control group(n=53),and the patients who received high-frequency ultrasound-guided labial gland biopsy from Mar.2023 to Dec.2024 were selected as ultrasound-guided group(n=73).The success rate of sampling,the number of salivary lobes,wound healing time,and adverse reaction incidence were analyzed in the 2 groups.Results The success rate of sampling in the ultrasound-guided group(100.00％,73/73)was significantly higher than that in the control group(92.45％,49/53),the number of salivary lobes(6[6,7])was significantly greater than that in the control group(6[5,6]),and the wound healing time was significantly shorter than that in the control group(4[4,5]d vs 5[5,6]d)(all P＜0.05).One(1.37％)patient of the ultrasound-guided group had postoperative adverse reactions,and 5(9.43％)patients of the control group had adverse reactions,with no significant difference(P＞0.05).Conclusion High-frequency ultrasound can clearly locate labial gland,improve the success rate of sampling and shorten the wound healing time,and it is worthy of clinical promotion and application.

Objective To establish a rapid,sensitive,and specific multiplex PCR detection method for the simultaneous detection of Cryptosporidium,Eimeria,and bovine parvovirus.Methods Specific primers targeting the SSU rRNA genes of Cryptosporidium and Eimeria,as well as the VP2 gene of bovine parvovirus were designed and the corresponding recombinant plasmid standards were constructed.To establish the multiplex PCR method,the reaction conditions were optimized using temperature gradient PCR and single-variable control methods.The sensitivity,specificity,reproducibility,and clinical application of the protocol were evaluated.Results The optimal annealing temperature was found to be 60.5℃,and the forward and reverse primer concentrations were determined to be 0.2 μmol/L for Eimeria,and 0.4 μmol/L for Cryptosporidium and bovine parvovirus.The assay demonstrated high sensitivity,with detection limits of 243,260,and 3 110 copies for the recombinant plasmid standards of Cryptosporidium,Eimeria,and bovine parvovirus,respectively.Specificity testing showed no cross-reactivity with ten common bovine pathogens,including Salmonella,bovine viral diarrhea virus,and bovine rotavirus.Consistent intra-and inter-batch results confirmed the strong reproducibility of the method.Clinical application to 81 diarrhea samples from various regions in the Ganzi Prefecture,Sichuan,revealed positivity rates of 18.52%(15/81)for Cryptosporidium,34.57%(28/81)for Eimeria,and 18.52%(15/81)forbovineparvovirus,withamixedinfectionrateof3.7%(3/81).Conclusions Themultiplex PCR method established in this study offers a reliable tool for differential diagnosis and epidemiological investigation of the three common diarrheal pathogens in yaks.

Objective To study the mechanism of Sanhuang Decotion in the treatment of ulcerative colitis(UC)under Candida albicans colonization in mice based on Dectin-1-Syk-CARD9 signaling pathway.Methods Mice model of UC with fungal colonization were established with dextran sodium sulfate free drinking and C.albicans intragastric administration.Mice were divided into normal control group,model group,sulfasalazine group,fluconazole group,and Sanhuang Decotion low-and high-dosage groups,and receive corresponding drug interventions.General state of mice were observed,and the disease activity index(DAI)score of mice were calculated.The load of C.albicans in intestine was detected,the length of the colon was measured,and pathological scoring of the colon tissue was performed.The ultrastructural changes of colon epithelium were observed under transmission electron microscopy.The contents of TNF-α,IL-6 and IL-12 in serum and colon tissues were detected by ELISA.The mRNA and protein expression of Dectin-1,Syk,CARD9,NF-κBp65 and inflammation factors in intestinal epithelial cells and colon tissues were detected by qPCR,Western blot and immunohistochemistry.Results Compared with the normal control group,the model group mice showed reduced activity,decreased food intake,accompanied by loose stools,significantly increased DAI score,increased load of C.albicans in the intestine,shortened colon length,and increased histopathological score,with widening of gap between colon epithelial cells,cytoplasmic dissolution,mitochondrial swelling;TNF-α,IL-6 and IL-12 in serum and colon tissue increased,the expressions of Dectin-1 and CARD9 mRNA and protein in colon epithelial cells increased,p-Syk,p-NF-κBp65,CARD9,TNF-α,IL-1β,IL-6 protein expression in colon tissue increased(P<0.01,P<0.05).Compared with the model group,the Sanhuang Decotion high-dosage group mice showed a significant decrease in DAI score,decreased intestinal C.albicans load,increased colon length,decreased histopathological score,more complete and orderly arrangement of microvilli in colon epithelial cells,mild mitochondrial swelling,TNF-α,IL-6 and IL-12 in serum and colon tissue decreased,and the mRNA and protein expression of Dectin-1 and CARD9 in colon tissue increased,the expression of p-Syk,p-NF-κBp65,CARD9,TNF-α,IL-1β,IL-6 protein in colon tissue decreased(P<0.01,P<0.05).Conclusion Sanhuang Decotion may exert an anti C.albicans colonization UC effect by inhibiting the Dectin-1-Syk-CARD9 signaling pathway and reducing the release of inflammatory factors.

Objective To investigate the protective effect of cardamomine(CAR)on anthracycline-induced cardiotoxicity in rats by regulating the pyroptosis mediated by Notch/nuclear factor-κB(NF-κB)signal pathway.Methods The rat model of cardiotoxicity was established by intraperitoneal injection of doxorubicin(DOX).The model rats were randomly divided into DOX group,CAR-L group,CAR-H group and Jagged1 group.Another 10 rats were taken as the control group.The control group and the DOX group were given the same amount of 0.9％NaCl.The CAR-L group and CAR-H group were given 40 and 80 mg·kg-1 CAR by gavage,respectively.The Jagged1 group was given 80 mg·kg-1 CAR+and 25 ng·kg-1 Jagged1 by gavage once a day for 4 weeks.Myocardial injury markers creatine kinase isoenzyme(CK-MB)and troponin Ⅰ(cTn Ⅰ)were detected by kit.The expression of pyroptosis protein Nod-like receptor protein 3(NLRP3)and desquamate D(GSDM-D)were observed by immunohistochemistry.The expression of Notch1 and phosphorylated NF-κB p65(p-NF-κB p65)protein in myocardial tissue was detected by Western blotting.Results The levels of CK-MB in control group,DOX group,CAR-L group,CAR-H group and Jagged1 group were(48.51±5.39),(175.93±13.27),(106.83±9.73),(83.71±8.39)and(126.08±9.74)U·L-1;the levels of cTn Ⅰ were(1.95±0.18),(12.46±1.83),(7.15±0.64),(4.13±0.38)and(8.01±0.78)ng·mL-1;the average optical density of NLRP3 protein were 0.19±0.07,0.36±0.05,0.25±0.05,0.21±0.03 and 0.31±0.06;the average optical density of GSDM-D were 0.18±0.04,0.43±0.06,0.24±0.03,0.19±0.04 and 0.32±0.05.There were significant differences in the above indexes between DOX group and control group(all P＜0.05).There were significant differences in the above indexes between CAR-L group,CAR-H group and DOX group(all P＜0.05),and there were significant differences between CAR-L group and CAR-H group(all P＜0.05).The above indexes in Jagged1 group were significantly different from those in CAR-H group(all P＜0.05).Conclusion CAR can improve myocardial injury in DOX cardiotoxic rats,reduce oxidative stress,inflammatory reaction and pyroptosis,and its mechanism may be related to the inhibition of Notch/NF-κB pathway.

Objective:Fatigue is one of the common disabling non-motor symptoms of multiple system atrophy(MSA).This study aimed to investigate the prevalence of fatigue in MSA patients and its relationship with anxiety and depression.Methods:In this cross-sectional study, 44 MSA inpatients from Xuanwu Hospital of Capital Medical University were enrolled.Fatigue was defined as a Fatigue Severity Scale(FSS)score ≥4.The motor symptoms of the patients were evaluated using the Unified Parkinson's Disease Rating Scale(MDS-UPDRS)and Unified Multi-System Atrophy Rating Scale(UMSARS).The Hamilton Rating Scale for Depression(HAMD), Geriatric Depression Scale(GDS)and Hamilton Anxiety Scale(HAMA)were used to assess anxiety and depression.Results:The mean age of the MSA patients was 60.1±6.4 years, and the score of FSS was 4.3±2.4, with 28 patients(63.6%)having fatigue.Compared with the non-fatigue group, the fatigue group showed clear anxiety(HAMA: 16.5±8.9 vs.9.4±5.0, t=-2.292, P=0.010)and depression(HAMD: 14.4±7.0 vs.8.4±3.4, t=6.192, P=0.017; GDS: 18.2±7.4 vs.10.7±5.2, t=-3.560, P=0.044).The severity of fatigue in MSA patients was positively correlated with anxiety( r=0.516, P<0.001), depression(HAMD: r=0.551, P<0.001; GDS: r=0.636, P=0.000)and the score of activities of daily living( r=0.320, P=0.034), but not correlated with motor symptoms or disease severity. Conclusions:Nearly two-thirds of MSA patients have symptoms of fatigue, and fatigue is significantly associated with levels of anxiety and depression, affecting patients' mood and activities of daily living.

Multiple system atrophy(MSA)is a rapidly progressive neurodegenerative disease and, along with Parkinson's disease(PD)and dementia with Lewy bodies(DLB), belongs to the group of α-synucleinopathies.Due to an overlap of clinical symptoms of similar diseases in the early stages and a lack of sensitivity of the current diagnostic criteria to detect the disease in the early stages, difficulties abound in conducting clinical trials on disease-modifying therapeutic agents for its early treatment, and progress in the development of disease-modifying therapeutic agents as well as the development and validation of diagnostic tools has been slow.Consequently, the International Movement Disorder Society(MDS)has introduced new diagnostic criteria for MSA, which, for the first time, propose a category known as possible prodromal MSA and its diagnostic criteria.This review described the diagnostic criteria for possible prodromal MSA and its differential diagnosis from other prodromal α-synucleinopathies, in order to improve the accuracy of diagnosis in the early stages and to promote research on the early stages of the disease.