Mitochondrial diseases are a group of hereditary disorders characterized by impaired oxidative phosphorylation in the mitochondrial respiratory chain caused by defects in either mitochondrial DNA or nuclear DNA， and such diseases have complex and diverse clinical manifestations and often involve multiple organs and systems， with the main manifestation of lesions in the nervous system and muscles due to their high energy demands. At present， there is still a lack of effective therapies for most mitochondrial diseases， and therefore， multidisciplinary management is essential in clinical practice， integrating various therapeutic approaches to provide personalized treatment regimens for patients with mitochondrial diseases. The primary treatment principle involves the timely correction of pathological and physiological abnormalities through pharmacological interventions， dietary modifications， and exercise management， along with the prompt treatment of system-specific impairments and the prevention of potential complications.
Diagnosis

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective To analyze the correlations between platelet-related parameters and the incidence of anxiety and depression in the patients undergoing peritoneal dialysis(PD),and evaluate the efficacy of the pa-rameters in the diagnosis of anxiety and depression in PD patients.Methods A total of 245 patients undergoing PD in the First Affiliated Hospital of Hebei North University from September 2022 to February 2023 were enrolled.The gener-alized anxiety scale(GAD-7)and the patient health questionnaire(PHQ-9)were used to evaluate the anxiety and depression of the patients,respectively.The personal information and biochemical indicators of the patients were col-lected,and the platelet count(PLT),mean platelet volume(MPV),and platelet distribution width(PDW)were measured.Logistic regression was adopted to analyze the relationships of platelet-related parameters with anxiety and depression in PD patients.Results Among the 245 patients undergoing PD,the incidences of anxiety and depression were 15.9% and 38.0% ,respectively.There were differences in the dialysis period(Z=-2.358,P =0.018;Z =-3.079,P=0.002),MPV(Z=-4.953,P<0.001;Z=-7.878,P<0.001),and PDW(Z =-4.587,P<0.001;Z=-7.367,P<0.001)between the anxiety group and the non-anxiety group as well as between the de-pression group and the non-depression group.The correlation analysis showed that MPV(r =0.358,P<0.001;r =0.489,P<0.001)and PDW(r =0.340,P<0.001;r =0.447,P<0.001)were positively correlated with anxiety and depression in the patients undergoing PD.The Logistic regression model showed that MPV(P =0.022,P =0.011),PDW(P =0.041,P =0.018),and dialysis period(P =0.011,P =0.030)were independent risk factors for the anxiety and depressive state in PD patients.The areas under the receiver operating characteristic curve of MPV in the diagnosis of anxiety and depression in PD patients were 0.750 and 0.800,respectively,and those of PDW were 0.732 and 0.780,respectively.Conclusion MPV and PDW have high efficacy in the diagnosis of anxiety and depression associated with PD and can be used as objective indicators to evaluate the anxiety and depression in the patients undergoing PD.

Objective:To elucidate the phenomenon that epileptic seizure occurs in patients with epilepsy without definite diagnosis when driving a motor vehicle and its hazards.Methods:From January 2020 to June 2022, 7 epileptic patients who experienced traffic accidents caused by seizures were selected from the First Affiliated Hospital of Soochow University, and their demographic data, traffic accident related data and epilepsy diagnosis and treatment data were summarized and analyzed.Results:A total of 7 adult patients with epilepsy were collected, including 6 males, 4 of whom had been driving for more than 10 years. Among them, 1 patient drove a bus, and the other 6 patients drove private cars. Totally 5/7 of the accidents resulted in personal injury, and 3/7 of the accidents resulted in personal death. In 5 patients, video electroencephalogram showed interictal epileptiform discharges. In 2 patients, the imaging findings suggested the presence of cerebral cortical lesions that may lead to seizures. In terms of the form of seizure, 3 patients′ seizure type was focal to bilateral tonic-clonic, and the other 4 patients were very probable to be focal impaired awareness seizure.Conclusions:Undiagnosed epileptic seizures lead to traffic accidents, endanger patients and public safety, which need to attract attention from both doctors and patients, as well as the whole society.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS^E） technique， we identified qualitatively the metabolites of aristolochic acid（AAs） in rat in order to analyze the metabolic differences between water extract of Aristolochiae fructus（AFE） and Aristolochic acid Ⅰ（AAⅠ）. MethodSD rats were selected and administered AFE（110 g·kg^-1·d^-1） or AAⅠ（5 mg·kg^-1·d^-1） by oral for 5 days， respectively. Serum， urine and feces were collected after administration. Through sample pretreatment， ACQUITY UPLC BEH C₁₈ column（2.1 mm×100 mm， 1.7 μm） was used with the mobile phase of 0.01% formic acid methanol（A）-0.01% formic acid water（B， containing 5 mmol·L^-1 ammonium acetate） for gradient elution（0-1 min， 10%B； 1-7 min， 10%-75%B； 7-7.2 min， 75%-95%B； 7.2-10.2 min， 95%B； 10.2-10.3 min， 95%-10%B； 10.3-12 min， 10%B） at a flow rate of 0.3 mL·min^-1. Positive ion mode of electrospray ionization（ESI⁺） was performed in the scanning range of m/z 100-1 200. In combination with UNIFI 1.9.4.053 system， the Pathway-MS^E was used to qualitatively analyze and identify the AAs prototype and related metabolites in biological samples（serum， urine and feces）， and to compare the similarities and differences of metabolites in rats in the subacute toxicity test between AFE group and AAⅠ group. ResultCompared with AAⅠ group， 6， 10， 13 common metabolites and 14， 20， 30 unique metabolites were identified in biological samples（serum， urine and feces） of AFE group， respectively. Moreover， the main AAs components always followed the metabolic processes of demethylation， nitrate reduction and conjugation. Compared with common metabolites in AAⅠ group， prototype components of AAⅠ in serum and most metabolic derivatives of AAⅠ［AAⅠa， aristolochic lactam Ⅰ（ALⅠ）a， 7-OHALⅠ and its conjugated derivatives］ in biological samples were significantly increased in AFE group（P<0.05， P<0.01）， except that the metabolic amount of ALⅠ in feces of AFE group was remarkably lowed than that of AAⅠ group（P<0.01）. In addition， a variety of special ALⅠ efflux derivatives were also identified in the urine and feces of the AFE group. ConclusionAlthough major AAs components in AFE all show similar metabolic rules as AAⅠ components in vivo， the coexistence of multiple AAs components in Aristolochiae Fructus may affect the metabolism of AAⅠ， and achieve the attenuating effect by increasing the metabolic effection of AAⅠ and ALⅠ.

Objective:To observe the path and anatomic distribution of cutaneous branch of second dorsal metacarpal artery(SDMA) from the back of hand to the web of the fingers, and to explore the feasibility and clinical effect on the transfer of free flap of SDMA.Methods:Between June 2018 and September 2018, with perfusion of red latex, 22 hand specimens were dissected to explore the course, vessel calibre and distribution of cutaneous branches of SDMA, and to discover the existence of an innervation of cutaneous nerve in Department of Hand Surgery of Tangshan Second Hospital. Later on, from February 2019 to July 2020, 2 thumb pulp defects of 2 patients were reconstructed with the free flaps of SDMA. One defect was in the left thumb and the other in the right, both were male and compression injuries. Size of thumb pulp and a skin defect was at 3.5 cm×2.0 cm in 1 patient, and 2.0 cm×2.5 cm in the other. There was no neurovascular injury, but 1 patient had a distal phalangeal fracture and a nail bed laceration. The sizes of the flaps were 3.8 cm×2.3 cm and 2.8 cm×2.5 cm. Functional exercises started from 3 weeks after surgery. Patients attended postoperation follow up regularly by outpatient visit, telephone or internet interviews. Follow-up observations included the appearance, texture, sensory recovery of the flaps and thumb functions.Results:Multiple perforating branches (4-9 branches) were found from SDMA, which distributed in the distal 1/3 of SDMA in the anatomic study. It was found that the outer diameter of SDMA was 0.76 mm±0.25 mm at the intersection of extensor tendon of index finger and that of the digital web artery was 0.71 mm±0.12 mm. The length of digital web artery was 11.00 mm±1.27 mm. The 2 surgically transferred flaps were all survived. One patient showed the function of thumb in excellent with two-point discrimination (TPD) at 7.0 mm, at 18 months of follow-up. The other patient showed good thumb movement, soft and elastic skin of the flap and with a 7.5 mm in TPD, at 15 months of follow-up. According to the Evaluation Standard of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, the results of the 2 flaps were all excellent.Conclusion:The flap of SDMA has a constant cutaneous nerve and a long vascular pedicle with an ideal vessel size. It is suitable for free transfer and can be used to reconstruct soft tissue defects of thumb.

Objective     To investigate the effect of ginkgolide B (GB) on cysteinyl aspartate specific proteinase-3 (Caspase-3)/chromosome 10 deletion phosphatase-tension protein homologue (PTEN)/protein kinase B (Akt) pathway and cell proliferation and apoptosis in hypoxia/reoxygenation cardiomyocytes. Methods     H9C2 cells were cultured in vitro. A control group was cultured in serum-free DMEM high glucose medium at 37°C and 5% CO2 for 28 hours. The remaining groups were prepared with hypoxia/reoxygenation models. A GB low-dose group and a GB high-dose group were treated with GB pretreatment with final concentration of 50 μmol/L and 200 μmol/L respectively at 1 h before hypoxia/reoxygenation. A carvedilol group was treated with carvedilol of a final concentration of 10 μmol/L at 1 h before hypoxia/reoxygenation. The proliferation and apoptosis of H9C2 cells were detected, and the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), reactive oxygen species (ROS), PTEN, Akt, phosphorylated Akt (p-Akt) and Caspase-3 in H9C2 cells were also detected. Results     Compared with the control group, the proliferation rate of H9C2 cell, and the levels of PTEN, Akt and p-Akt in other groups decreased, and the apoptosis rate, and the levels of LDH, MDA, ROS and Caspase-3 increased (P<0.05). Compared with the hypoxia/reoxygenation group, the proliferation rate of H9C2 cell, and the levels of PTEN, Akt and p-Akt in all GB dose groups and the carvedilol group increased; the apoptosis rate, and the levels of LDH, MDA, ROS and Caspase-3 decreased, and the effect of GB was in a dose dependent manner; however, the effect of GB was not as strong as carvedilol (P<0.05). Conclusion     GB can inhibit H9C2 cell apoptosis and promote H9C2 cell proliferation by activating Caspase-3/PTEN/Akt pathway.

OBJECTIVE: To explore the genetic etiology of recurrent hydatidiform mole (RHM) and provide accurate guidance for reproduction. METHODS: Peripheral venous blood samples of the probands with RHM and members from 5 unrelated pedigrees were collected. Genomic DNA was extracted by using routine method, and whole exome sequencing was carried out to detect variants of RHM-associated genes including NLRP7 and KHDC3L. Sanger sequencing and real-time quantitative PCR (RT-qPCR) were used to validate the candidate variants and delineate their parental origin. RESULTS: Homozygous or compound heterozygous variants of the NLRP7 gene were identified in four patients from three pedigrees, which included a homozygous deletion of exon 1 to 4 of NLRP7 in patient P1 and her elder sister, compound heterozygous variants of NLRP7 c.939delG (p.Q314Sfs*6) pat and c.1533delG (p.N512Tfs*4) mat in patient P2, and compound heterozygous variants of NLRP7 c.2389_2390delTC (p.A798Qfs*6) pat and c.2165A>G (p.D722G) mat in patient P4. All variants were interpreted as pathogenic or likely pathogenic according to the American College of Medical and Genomics (ACMG) guidelines. Among these, NLRP7 exons 1 to 4 deletion, c.939delG (p.Q314Sfs*6), c.1533delG (p.N512Tfs*4) and c.2389_2390delTC (p.A798Qfs*6) were unreported previously. CONCLUSION Variants of the NLRP7 gene probably underlay autosomal recessive RHM in the three pedigrees, and definitive molecular diagnosis is beneficial for accurate genetic counseling. Above finding has also enriched the spectrum of the NLRP7 variants underlying RHM.
Adaptor Proteins, Signal Transducing/genetics* ; Aged ; China ; Female ; Homozygote ; Humans ; Hydatidiform Mole/pathology* ; Mutation ; Pedigree ; Pregnancy ; Sequence Deletion

Type 1 diabetes mellitus (T1DM)-induced cognitive dysfunction is common, but its underlying mechanisms are still poorly understood. In this study, we found that knockout of conventional protein kinase C (cPKC)γ significantly increased the phosphorylation of Tau at Ser214 and neurofibrillary tangles, but did not affect the activities of GSK-3β and PP2A in the hippocampal neurons of T1DM mice. cPKCγ deficiency significantly decreased the level of autophagy in the hippocampal neurons of T1DM mice. Activation of autophagy greatly alleviated the cognitive impairment induced by cPKCγ deficiency in T1DM mice. Moreover, cPKCγ deficiency reduced the AMPK phosphorylation levels and increased the phosphorylation levels of mTOR in vivo and in vitro. The high glucose-induced Tau phosphorylation at Ser214 was further increased by the autophagy inhibitor and was significantly decreased by an mTOR inhibitor. In conclusion, these results indicated that cPKCγ promotes autophagy through the AMPK/mTOR signaling pathway, thus reducing the level of phosphorylated Tau at Ser214 and neurofibrillary tangles.
AMP-Activated Protein Kinases/metabolism* ; Animals ; Autophagy ; Diabetes Mellitus, Type 1 ; Glucose ; Glycogen Synthase Kinase 3 beta/metabolism* ; Mice ; Phosphorylation ; Protein Kinase C/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; tau Proteins/metabolism*