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

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 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*

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 clinical results in reconstruction of finger C-shape soft tissue defect with the wrist crease free flap carrying cutaneous nerve.Methods:From June, 2017 to April, 2019, 7 fingers(7 patients) with C-shape defect were treated with the wrist crease free flap carrying cutaneous nerve. The size of defect ranged from 1.0 cm × 2.5 cm-2.2 cm × 4.0 cm; the flap sizes were 1.3 cm × 2.7 cm-2.5 cm × 4.5 cm. Five fingers had unilateral defect of proper palmar digital artery. Two fingers that had bilateral defect of proper palmar digital artery with poor blood circulation were re-established with blood supply by Flow-through flaps. Four fingers had unilateral defect of proper palmar digital nerves, and 3 had bilateral defect of proper palmar digital artery. Five of the fingers were repaired by the superficial branch of the radial nerve and 2 repaired by palmar cutaneous branch of median nerve. Regular outpatient follow-up was conducted after surgery for 8 to 15 (mean 11) months.Results:All the fingers and flaps survived with primary healing. Numbness existed in the areas of functional dominance of the cutaneous nerve. At the end of follow-up, the flaps showed good texture without significant bloated appearance with the recovery of protective sensation. The sensation of fingertip recovered to S 4 in 5 fingers and S 3+ in 2 fingers. Finger pulps were plump. All of the fingers moved freely. Linear scars were observed at donor sites and the wrists moved freely. Numbness feeling in the areas of cutaneous nerve disappeared at 6 to 8 weeks after surgery. According to the Functional Evaluation Criteria of the Finger Replantation published by the Hand Surgery Society of the Chinese Medical Association, the results were excellent in 6 fingers and good in 1 finger. Conclusion:The wrist crease free flap carrying cutaneous nerve is constant and can be dissected transversely to reconstruct and fit the C-shape defect of finger. It can re-establish the blood supply as well as to repair the proper palmar digital nerve defect at the same time.

Objective:To investigate the application value of dual-graft living donor liver transplantation of right segment from an adult living donor combined with a left lateral segment from donation after brain death for hepatocellular carcinoma (HCC).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of a male 46-year-old patient with HCC who underwent dual-graft living donor liver transplantation of right segment from an adult living donor combined with a left lateral segment from donation after brain death at the West China Hospital of Sichuan University in October 2019 were collected. He weighed 66 kg and was 171 cm in height. His blood type was A Rh-positive. Graft one was from a female 23-year-old living donor who had a bodyweight of 50 kg, a height of 150 cm, and blood type of A Rh-positive; graft two was from a male 44-year-old brain death donor with the blood type of A Rh-positive. The surgery was performed in three operating rooms, graft one and graft two were obtained simultaneously in two operating rooms, and the recipient′s liver was dissected in the third operating room. When the in vitro splicing of the liver was almost completed, surgeons entirely removed the recipient′s liver and started to transplant the new one. Observation indicators: (1) surgical situations and postoperative recovery of the living donor and the recipient; (2) postoperative pathological examination of the recipient′s liver; (3) follow-up. Follow-up was conducted by outpatient examinations, including monitoring of HCC recurrence, monitoring of new liver function, monitoring and adjustment of immunosuppressive agents, detection of biliary vascular complications, rejection and adverse drug reactions. Regular lifelong follow-up was required for recipients, with the latest follow-up on December 4, 2019. Count data were expressed as absolute numbers or percentages.Results:(1) Surgical situations and postoperative recovery of the living donor and the recipient: operation time, volume of intraoperative blood loss, volume of intraoperative infusion of autologous blood of the living donor were 315 minutes, 200 mL, 200 mL, respectively. The living donor was discharged from hospital on the sixth day after surgery without any complications. The recipient underwent modified piggyback liver transplantation successfully. Graft one was from the right segment free of the middle hepatic vein in the living donor, with a weight of 410 g. Graft two was from the left lateral segment in the donor after brain death, with a weight of 400 g. The graft from donors to recipient weight ratio was 1.2% after splicing. The operation time, duration of anhepatic phase, volume of intraoperative blood loss, volume of intraoperative blood transfusion were 815 minutes, 60 minutes, 1 500 mL, 1 800 mL, respectively. The recipient′s temperature was normal during hospitalization. On the first postoperative day, the level of white blood cell and neutrophilic granulocyte percentage of the recipient reached a peak (17.15×10 9/L and 91.7%, respectively) and then gradually decreased. After anti-infective treatment with piperacillin sodium and sulbactam sodium, both of the two indicators returned to normal on the seventh day after surgery (7.90×10 9/L and 70.9%, respectively), and the antibiotic was discontinued. During the hospitalization, the level of albumin of the recipient fluctuated in 31.0-41.4 g/L, the liver function parameters including total bilirubin, alanine aminotransferase, aspartate aminotransferase, prothrombin time and international normalized ratio gradually returned to normal levels, and the renal function parameters including creatinine and estimated glomerular filtration rate remained within the normal range. On the tenth day after surgery, the recipient was in good condition and discharged from the hospital. (2) Postoperative pathological examination of the recipient′s liver: ① results of the pathological examination showed moderately differentiated HCC with incomplete tumour capsule and no invasion of the liver capsule. The surrounding liver tissues showed hepatitis B-related nodular cirrhosis, and no tumor involvement was detected at the broken end of the hilum. ② The gallbladder presented chronic cholecystitis accompanied by cholesterol deposition, and one abdominal lymph node showed reactive hyperplasia. The immunohistochemical staining showed 10% positive HBsAg and negative HBcAg. (3) Follow-up: the tumor markers of the recipient were tested on November 19, 2019, including α-fetoprotein (2.92 μg/L) and abnormal prothrombin (16 AU/L). Together with the negative result of abdominal colour doppler ultrasound, they collectively indicated no HCC recurrence in the recipient. The liver function parameters including total bilirubin (8.6 μmol/L), alanine aminotransferase (23 IU/L), aspartate aminotransferase (28 IU/L) and albumin (44.0 g/L) of the recipient tested on December 3, 2019, were all in normal levels. Blood concentration of tacrolimus was 4.2 μg/L . The drug dose of mycophenolate mofetil dispersible tablets was adjusted to 250 mg given twice daily, and the drug dose of others was unchanged (tacrolimus 2 mg, once daily; sirolimus 1mg, once daily). No symptoms, signs or examination results indicated biliary vascular complications, rejection or adverse drug reactions. Conclusion:Dual-graft living donor liver transplantation of right segment from an adult living donor combined with a left lateral segment from donation after brain death is safe and effective, which can be used as a suboptimal treatment for patients with HCC beyond Milan criteria.