BackgroundCognitive function is closely related to an individual's quality of life and social functioning， with approximately 20%~35% of patients with depressive disorder experiencing some degree of cognitive impairment even after clinical symptom remission. Existing evidence suggests that tACS can improve specific cognitive domains， such as memory function， while its effects on other cognitive dimensions， such as executive functioning， attention， and information processing speed， remain unclear. ObjectiveTo explore the effects of tACS on the multidimensional cognitive functions and emotional problems of patients with depressive disorder， thus to provide references for the treatment of depressive disorder. MethodsForty-nine patients with depressive disorder who were hospitalized in the Fourth People's Hospital of Wuhu from November 2022 to October 2024 and met the diagnostic criteria for depressive disorder outlined in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， were selected as study participants. Subjects were randomly divided into study group （n=23） and control group （n=26） based on Microsoft Excel. Both groups received sertraline treatment. The initial dose was 50 mg/day， which gradually titrated upward based on individual variability， drug tolerance， and therapeutic response， with a maintenance dose ranging from 100 to 200 mg/day. In addition， the study group underwent tACS therapy for 4 weeks， with 5 sessions per week， each lasting 20 minutes. The control group received sham stimulation， in which the stimulus was interrupted after the first 30 seconds. At baseline， the 4^th week， and the 12^th week of treatment， patients were assessed using the Hamilton Depression Scale-17 item （HAMD-17）， Hamilton Anxiety Scale （HAMA）， and MATRICS Consensus Cognitive Battery （MCCB）. ResultsRepeated measures analysis of variance indicated that both the time effect and the time×group interaction effect for HAMD-17 scores were statistically significant between the two groups （F=260.437， 25.309， P<0.01）. At week 12 of treatment， the HAMD-17 score in the study group was lower than that in the control group （t=4.236， P<0.01）. For HAMA scores， the time effect， group effect， and time×group interaction effect were all statistically significant between the two groups （F=248.082， 4.506， 9.500， P<0.05 or 0.01）. At weeks 4 and 12， study group reported lower HAMA scores compared with control group （t=4.580， 2.608， P<0.05 or 0.01）. Regarding the MCCB scores for attention/vigilance， verbal learning， and overall composite， the time effect， group effect， and time×group interaction effect were all statistically significant between the two groups （F=70.331， 27.882， 51.679， 5.560， 10.948， 7.860， 8.490， 3.874， 5.025， P<0.05 or 0.01）. After intervention， the study group showed significantly higher MCCB scores for attention/vigilance， verbal learning， and overall composite at both week 4 （t=-2.149， -3.530， -2.740， P<0.05） and week 12 （t=-3.534， -3.576， -3.838， P<0.01） when compared to the control group. ConclusionThe combined tACS and sertraline therapy may demonstrate superior efficacy to pharmacotherapy alone in the short term for improving attention/vigilance， verbal learning， overall cognitive function， and anxiety symptoms in patients with depressive disorders. Based on the 12-week outcomes， the combined tACS and sertraline therapy not only sustaine its previously observed advantages in improving cognitive domains and anxiety symptoms， but also demonstrate potentially superior efficacy over monotherapy in alleviating depressive symptoms. ［Fund by Clinical Medical Research Transformation Special Project of Anhui Province （number， 202204295107020065）］

OBJECTIVE: To investigate the safety and prognostic factors influencing the treatment of upper urinary tract urothelial carcinoma (UTUC) combined with bladder cancer (BCa) by laparoscopic simultaneous radical cystectomy and nephroureterectomy (RCNU). METHODS: The clinical data of patients admitted to Peking University Third Hospital for laparoscopic RCNU surgery from January 2009 to September 2023 were analyzed retrospectively. Based on the same gender, age (±5 years), history of uroepithelial tumors, underlying diseases, T-stage, N-stage, M-stage, American Society of Anesthesiologists (ASA) score, Charlson comorbidity index, and body mass index (BMI) (±5), 34 patients with RCNU were matched 1 ∶1 with patients with bladder cancer who underwent laparoscopic radical cystectomy (RC) alone. Kaplan-Meier survival analysis was used to calculate patient survival, and Cox proportional regression risk model was used to analyze clinical factors affecting prognosis. RESULTS: Of the 68 patients enrolled, the follow-up rate was 100% with a median follow-up time of 27.0 (11.7, 60.2) months. Comparison of intraoperative conditions (including operation time, estimated intraoperative bleeding, intra-operative blood transfusion, etc.) between the two groups of patients showed no significant difference (P>0.05). Comparison of preoperative creatinine and postoperative creatinine between the two groups of patients showed significant differences (P < 0.05). The perioperative Clavien grade Ⅲ-Ⅳ complication rates were 2.9% (1/34) in the RC group and 5.9% (2/34) in the RCNU group. There was no significant difference in terms of perioperative complications between the two groups. Overall survival was significantly lower in the patients receiving RCNU compared with the matched group receiving RC alone (P < 0.05). Cox regression analysis suggested that two factors, high N stage and high postoperative creatinine, were independent risk factors affecting the prognosis of patients in the 2 groups (P < 0.05). CONCLUSION The overall survival prognosis of patients undergoing RCNU surgery was worse compared with laparoscopic RC surgery alone during the same period. There was no clinically significant difference between the two groups in terms of operation time, intraoperative bleeding, and perioperative complications, and there were clinically significant differences in preoperative renal function and post-operative renal function.
Humans ; Laparoscopy/methods* ; Nephroureterectomy/methods* ; Cystectomy/methods* ; Prognosis ; Male ; Retrospective Studies ; Female ; Urinary Bladder Neoplasms/mortality* ; Middle Aged ; Aged

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER ^T2 /Parkin ^fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.

OBJECTIVES: To investigate the mechanism underlying the therapeutic effect of electroacupuncture (EA) on post-traumatic stress disorder (PTSD) in rats. METHODS: Forty male SD rats were randomized equally into blank control group, PTSD model group, sham-acupuncture group, paroxetine group, and EA group. In the latter 3 groups, the rat models of PTSD, induced by continuous single-prolonged stress and plantar electrical stimulation, were treated with EA at GV20, GV24, BL18 and BL23 acupoints for 15 min (5 times a week for 3 weeks), sham-acupuncture without electrical stimulation, or gavage with paroxetine suspension on the same schedule. Behavioral changes of the rats were evaluated using open field test (OFT) and elevated plus maze (EPM) test. Hippocampal pathologies and neuronal changes were examined with HE and Nissl staining, and mitochondrial ultrastructure was examined using electron microscopy. The mRNA and protein expression levels of Bcl-2, Bax, and caspase-3 were detected by RT-qPCR and immunofluorescence staining. RESULTS: The rat models of PTSD showed significantly reduced total distance traveled in OFT and distance and time spent in the open arms of the EPM, with decreased hippocampal neurons, obvious neuronal and mitochondrial pathologies, decreased hippocampal expression of Bcl-2, and increased Bax and caspase-3 expressions. Treatments with paroxetine and EA both significantly improved behavioral changes of the rat models, increased the number of Nissl-stained neurons, obviously alleviated pathologies in the hippocampal neurons and mitochondrial ultrastructure, increased hippocampal Bcl-2 expression, and lowered caspase-3 expressions. Paroxetine showed significantly better effect than EA for improving performance of the rats in EPM test, whereas sham-acupuncture did not produce any significant improvement. CONCLUSIONS EA alleviates PTSD in rats possibly by upregulating Bcl-2 and downregulating Bax and caspase-3, thereby ameliorating hippocampal mitochondrial damage.
Animals ; Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Hippocampus/pathology* ; Rats, Sprague-Dawley ; Male ; Rats ; Mitochondria/pathology* ; Signal Transduction ; bcl-2-Associated X Protein/metabolism* ; Caspase 3/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Disease Models, Animal

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*

Adenomyosis is a common gynecological disease characterized by the invasion of endometrial glands and stroma into the myometrium of uterus, the pathological mechanism of which remains unclear yet. Disturbed lipid metabolism extensively affects abnormal cell proliferation and invasion in various diseases. However, the lipidome signature of human myometrium, which could be crucial in the development of adenomyosis, remains unknown. In this study, we generated the first lipidome profiling of human myometrium using a high-coverage and quantitative lipidomics approach based on ultra-performance liquid chromatography (UPLC) coupled with triple quadrupole (QqQ)-mass spectrometry (MS). A total of 317 lipid species were successfully quantified in the myometrial tissues from women with (n = 38) or without (n = 65) adenomyosis who underwent hysterectomy at Peking Union Medical College Hospital (Bejing, China). Up to 83 lipid species showed significant alternations in content between the two groups. These lipid aberrations involved multiple metabolic pathways, and emphasized inflammation, cell migration, and immune dysregulation upon adenomyosis. Moreover, receiver operating characteristic (ROC) curve analysis found that the combination of five lipid species could accurately distinguished the myometrial samples from women with and without adenomyosis with an area under the curve (AUC) of 0.906. Desorption electrospray ionization MS imaging (MSI) further underscored the heterogeneous distributions of these lipid markers in the adenomyosis lesion and adjacent myometrial tissue. Collectively, these results extremely improved our understanding on the molecular basis of adenomyosis, and could shed light on developing potential biomarkers and new therapeutic directions for adenomyosis.

Objective:To explore the effects of imperatorin(IMP)on airway remodeling in the bronchial asthma mice,and to elucidate the possible mechanisms.Methods:Forty SFP male BALB/c mice were randomly divided into control group,model group,low dose of IMP group(IMP-L group),high dose of IMP group(IMP-H group)and dexamethasone group,with 8 mice in each group.Except for contol group,the mice in the other groups were injected with an ovalbumin(OVA)suspension intraperitoneally to induce the asthma models.After one week,the daily asthma symptoms of the mice were observed and scored.After 8 weeks,the enhanced pause(Penh)values of the mice in various groups were detected to evaluate the airway reactivities.The percentages of eosinophils in the bronchoalveolar lavage fluid(BALF)of the mice in various groups were detected by flow cytometry.The levels of serum IgE,interleukin interferon-gamma(IL)-13,IL-5,IL-4 and interferon-gamma(IFN-γ)in BALF of the mice in various groups were measured by enzyme-linked immunosorbent assay(ELISA)method.HE,PAS and Masson staining were applied to observe the pathomorphology,the number of goblet cells and collagen deposition of the lung tissue of the mice in various groups.Immunohisto chemistry method was applied to detect the expressions of α-smooth muscle actin(α-SMA)and mouse mammary tumor virus(MMTV)wingless type MMTV intergration site family member 5A(Wnt5A)proteins in lung tissue of the mice in various groups.The expression levels of Wnt5A,cellular myelocytomatosis oncogene(c-Myc),β-catenin and α-SMA in lung tissue of the mice in various groups were detected by Western blotting method.The expression levels of α-SMA protein in lung tissue of the mice in various groups were detected by immunofluorescence method.Results:Compared with control group,the score of asthma symptoms of the mice in model group was increased(P<0.01);the Penh value was significantly increased(P<0.01);the serum IgE levels and the levels of IL-13,IL-5,IL-4 in BALF,as well as the percentage of eosinophils(EOS)in BALF were significantly increased(P<0.05 or P<0.01),and the level of IFN-γ was reduced(P<0.05);the expression levels of α-SMA and Wnt5A proteins in lung tissue were markedly increased(P<0.01);the expression levels of proteins associated with the Wnt/β-catenin signaling pathway in the lung tissue were significantly increased(P<0.01);the immofluorescence method results showed the expression level of α-SMA protein in lung tissue was significantly increased(P<0.01).Compared with model group,the scores of asthma symphtoms of the mice in IMP-L group,IMP-H group,and dexamethasone group were decereased(P<0.01),and the Penh values of the mice in IMP-H group were decreased(P<0.05);the serum IgE levels and the levels of IL-13,IL-5,IL-4 in BALF,as well as the percentages of EOS in BALF of the mice in IMP-L group,IMP-H group,and dexamethasone group were decreased(P<0.05 or P<0.01),and the levels of IFN-γ were increased(P<0.05);the expression levels α-SMA and Wnt5A proteins in lung tissue were decreased(P<0.05 or P<0.01);the expression levels of proteins related to the Wnt/β-catenin signaling pathway in the lung tissue were decreased(P<0.05 or P<0.01);the immunofluorescence method results showed that expression levels of the α-SMA protein in the lung tissue were reduced(P<0.05 or P<0.01).Conclusion:IMP has an improving effect on airway remodeling in the asthmatic mice and can inhibit the expression levels of Wnt/β-catenin pathway-related proteins.

Objective To explore the short-term efficacy and safety of programmed death receptor-1(PD-1)antibody combined with chemoradiotherapy in early high-risk nasal extranodal natural killer/T cell lymphoma(ENKTCL,Nomogram modified risk index ≥1).Methods This study was a prospective phase Ⅱclinical study.A total of 20 patients with stage Ⅰ/Ⅱ nasal ENKTCL initially treated in the Affiliated Hospi-tal of Guizhou Medical University from June 2021 to December 2023 were selected as the study subjects.They were given 3 cycles of PD-1 antibody+P-Gemox(pegaspargase+gemcitabine+oxaliplatin)regimen induced immunochemotherapy and 3 cycles of PD-1 antibody concurrent immunoradiotherapy,14 d/cycle.The com-plete response(CR)rate after 3 cycles of induced immunochemotherapy,CR rate after treatment,objective re-sponse rate(ORR)after 3 cycles of induced immunochemotherapy and ORR after comprehensive treatment,occurrence of adverse reactions and plasma Epstein-Barr virus DNA copy number were observed.Results Af-ter 3 cycles of induction immunochemotherapy,the CR rate was 35.0％(7/20)and ORR was 90.0％(18/20).After the concurrent immunoradiotherapy,the CR rate was 95.0％(19/20)and ORR was 100.0％(20/20).The adverse reactions were mainly the grade 1/2.the immune-related adverse reactions included 9 ca-ses of grade 1/2 hypothyroidism(45.0％),4 cases of grade 1 capillary vessel hyperplasia(20.0％),1 case(5.0％)of grade 2 infusion reaction,and no immune myocarditis occurred.All 7 cases of positive EBV DNA turned to negative after 3 cycles of induced immunochemotherapy.Conclusion PD-1 antibody combined with P-Gemox in the radiotherapy of early high-risk ENKTCL has a high short-term remission rate with good tol-erance for treatment.

OBJECTIVE: To investigate the clinical phenotypic and genetic characteristics of three children with Paroxysmal kinesigenic dyskinesia (PKD) and Self-limited familial infantile epilepsy (SeLIE) caused by PRRT2 gene mutation. METHODS: Three children with PKD and SeLIE caused by PRRT2 gene mutation (children 1-3) who were treated in the First Affiliated Hospital of Zhengzhou University from November 2022 to August 2023 were selected as the research subjects. A retrospective study was conducted to collect the clinical and family history data of the three children. 2 mL of peripheral venous blood from children 1-3 and parents of children 1-2 were collected (parents of children refused to undergo genetic testing and no blood samples were collected), genomic DNA was extracted, whole exome sequencing (WES) was performed, and Sanger sequencing method was used for verification. According to the Classification Standards and Guidelines for Genetic Variants formulated by the American Society of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the "ACMG Guidelines"), the pathogenicity of the variant loci detected in three children was rated, and the detrimental loci of the variant loci were analyzed by multiple bioinformatics software. This study has been approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No. 2024-KY-0881-002). RESULTS: The clinical data and genetic test results of the three children in this study are as follows. Child 1: female, age of onset of 4 months and 10 days, with seizures, manifested as sudden cessation of movements, staring in both eyes, cyanosis of the lips, paleness, and stiffness and shaking of limbs. The results of genetic testing showed that child 1 had maternal PRRT2 gene c.583_584dup (p.P196Afs*34) frameshift variant, which was rated as a pathogenic variant (PVS1 PM2_Supporting PP4) according to ACMG guidelines. According to the clinical manifestations and genetic test results of child 1, he was diagnosed with SeLIE and took oral sodium valproate [0.5 mL/(kg.d)], and was still taking medication at the follow-up of 2 years old, and did not have seizures again after 5 months of age. Child 2: male, age of onset of 10 years old, manifested as dystonia after sudden movement. The results of genetic testing showed that child 2 had PRRT2 gene mutations: paternal c.649dupC (p.R217Pfs*8) frameshift variant and maternal c.445C>A (p.Q149K) mutation. Among them, c.649dupC was a reported pathogenic variant, and according to ACMG guidelines, c.445C>A variant was rated as a variant of unknown clinical significance (PM2_Supporting), with a high probability of benignness. According to the clinical manifestations and genetic test results of the child 2, he was diagnosed with PKD, and was followed up with oral oxcarbazepine 9 mg/(kg.d) until 12 years and 2 months, and was still on the drug, and there was no recurrence of the seizure of the form of dyskinesia after taking the drug. Child 3: male, age of onset of 11 years old, manifested by dystonia after sudden exercise. The results of genetic testing showed that child 3 had a missense variant of PRRT2 gene c.904G>C (p.D302H), and his parents refused genetic testing, and the source of the mutation was unknown, and the variant was rated as a variant of unknown clinical significance (PM2_Supporting+PP3_Moderate+PP4) according to ACMG guidelines. According to the clinical manifestations and genetic test results of child 3, he was diagnosed with PKD, and was treated with oral oxcarbazepine 10 mg/(kg.d) for 1 year and then discontinued on his own, and was followed up at the age of 17, and there was no recurrence of the seizure of the form of movement disorder after taking the drug. CONCLUSION One case of SeLIE and two cases of PKD caused by PRRT2 gene mutations responded well to anti-seizure drugs. In this study, four variant loci of PRRT2 gene were found: c.583_584dup, c.904G>C, c.649dupC, c.445C>A, among which c.583_584dup were new variants, enriching the variant spectrum of PRRT2 gene.
Humans ; Male ; Nerve Tissue Proteins/genetics* ; Female ; Membrane Proteins/genetics* ; Mutation ; Child, Preschool ; Infant ; Phenotype ; Dystonia/genetics* ; Retrospective Studies ; Child