Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective To analyze the clinical effect of inhaled ipratropium bromide in the treatment of patients with non-small cell lung cancer(NSCLC)combined with chronic obstructive pulmonary disease(COPD)and its protective effect on lung function.Methods Clinical data of patients with NSCLC complicated with COPD were retrospectively analyzed.According to the different treatment using cohort methods,the patients were divided into control group and treatment group.After admission,the patients in control group completed the relevant examinations,received conventional anti-infection,oxygen inhalation,asthma,ambroxol injection and other comprehensive treatment,and could be given appropriate mechanical ventilation support according to the development of the patient's condition,and then underwent selective lobectomy.Treatment group inhaled ipratropium bromide treatment:The conventional treatment was the same as control group,combined with atomized ipratropium bromide solution for inhalation 500 μg twice a day,continuous treatment for 1 week,and then selective lobectomy was performed.The clinical efficacy,lung function,inflammatory factor levels and adverse drug reactions were compared between the two groups.Results There were 61 cases in control group and 63 cases in treatment group.After treatment,the total clinical effective rate in treatment group and control group were 76.19％(48 cases/63 cases)and 50.82％(31 cases/61 cases),with significant difference(P＜0.05).After treatment,the forced expiratory volume in the first second(FEV1)of treatment group and control group were(1.89±0.61)and(1.57±0.33)L;the percentage of FEV1 in forced vital capacity(FEV1/FVC)were(73.36±6.58)％and(63.69±6.21)％;peak expiratory flow(PEF)were(3.74±0.81)and(3.24±0.50)L·s-1;interleukin-6(IL-6)were(102.51±7.03)and(133.25±7.75)ng·L-1;hypersensitive C-reactive protein(hs-CRP)were(8.24±2.36)and(18.54±2.31)ng·L-1;tumor necrosis factor-α(TNF-α)were(90.36±5.22)and(114.15±5.13)ng·L-1;white blood cell(WBC)were(91.45±9.31)x 109 and(121.16±9.88)x 109·L-1;the differences were all statistically significant(all P＜0.05).The total incidence of adverse drug reactions was 4.92％(3 cases/61 cases)in control group and 7.94％(5 cases/63 cases)in treatment group,with no statistical significance(P＞0.05).Conclusion Inhaled ipratropium bromide is effective in the treatment of NSCLC complicated with COPD,and has protective effect on lung function and good safety.

Objective To summarize the clinical and pathological characteristics of Langerhans cell histiocytosis(LCH)involving thyroid gland.Methods We reviewed 5 cases of histologically confirmed LCH with thyroid gland involvement in Huashan Hospital,Fudan University from Jun 2017 to Nov 2022 and analyzed their clinicopathological features.Results There were 1 male and 4 females aged from 29 to 54 years,with a median age of 31 years.Ultrasound showed hypoechoic nodules of thyroid.Morphologically,there were a large number of Langerhans cells,which contained abundant eosinophilic cytoplasm.The nucleus was oval,or had deeply grooved nuclei,which was like coffee beans.The nucleolus was not obvious,accompanied by a variable number of lymphocytes and eosinophils infiltration.The lesional cells were positive for CD1α,S100,Langerin,and Ki67 proliferation index was more than 15%,of which the highest was 70%.The tested 4 cases were all BRAF V600E and MAP2K1 gene mutation negative.Conclusion Cases limited to the thyroid were exceedingly rare.Most cases occurred in patients with multifocal disease.The clinical manifestations were painless enlargement of the thyroid gland.Surgical resection was a common treatment.Pathological manifestations included a large number of Langerhans cells and eosinophils diffused with the destruction of normal thyroid follicular structures.There was a characteristic of low mutation rates in BRAF V600E and MAP2K1 genes.

ObjectiveTemporal heterogeneity in lung cancer presents as fluctuations in the biological characteristics, genomic mutations, proliferation rates, and chemotherapeutic responses of tumor cells over time, posing a significant barrier to effective treatment. The complexity of this temporal variance, coupled with the spatial diversity of lung cancer, presents formidable challenges for research. This article will pave the way for new avenues in lung cancer research, aiding in a deeper understanding of the temporal heterogeneity of lung cancer, thereby enhancing the cure rate for lung cancer. MethodsRaman spectroscopy emerges as a powerful tool for real-time surveillance of biomolecular composition changes in lung cancer at the cellular scale, thus shedding light on the disease’s temporal heterogeneity. In our investigation, we harnessed Raman spectroscopic microscopy alongside multivariate statistical analysis to scrutinize the biomolecular alterations in human lung epithelial cells across various timeframes after benzo(a)pyrene exposure. ResultsOur findings indicated a temporal reduction in nucleic acids, lipids, proteins, and carotenoids, coinciding with a rise in glucose concentration. These patterns suggest that benzo(a)pyrene induces structural damage to the genetic material, accelerates lipid peroxidation, disrupts protein metabolism, curtails carotenoid production, and alters glucose metabolic pathways. Employing Raman spectroscopy enabled us to monitor the biomolecular dynamics within lung cancer cells in a real-time, non-invasive, and non-destructive manner, facilitating the elucidation of pivotal molecular features. ConclusionThis research enhances the comprehension of lung cancer progression and supports the development of personalized therapeutic approaches, which may improve the clinical outcomes for patients.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of liquiritin apioside,alibiflorin,swertiamarin,methyl gallate,benzoylpaeoniflorin,sweroside,6′-O-β-D-glucosylgentiopicroside,isoliquiritigenin,loganic acid,liquiritigenin,gallic acid,paeoniflorin,oxypaeoniflorin,gentiopicroside,glycyrrhizic acid,isoliquiritoside and liquiritin in Yangxue Ruanjian Capsules.METHODS The analysis was performed on a 40℃thermostatic Waters BEH C18column(2.1 mm×100 mm,1.7 μm),with the mobile phase comprising of 2 mmol/L ammonium acetate(containing 0.1%formic acid)-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in negative ion scanning with multiple reaction monitoring mode.RESULTS Seventeen constituents showed good linear relationships within their own ranges(r>0.999 6),whose average recoveries were 91.33%-104.03%with the RSDs of 1.58%-3.50%.CONCLUSION This rapid,accurate and stable method can be used for the quality control of Yangxue Ruanjian Capsules.

This paper summarizes the exploration process and academic significance of the academic thought of Zhou Zhongying,a master of traditional Chinese medicine,who took the creation of a new system of TCM pathogenesis theory as the core,and interprets its theoretical connotation.As a pioneer in the construction of higher education textbooks for traditional Chinese medicine,Professor Zhou Zhongying created the outline of TCM internal medicine viscera differentiation,persisted in carrying out innovative research on patho-genesis theory,achieved fruitful academic results,and enriched and developed the academic system of TCM theory.In the clinical di-agnosis and treatment of exogenous febrile diseases and acute and difficult internal injuries,he systematically created new pathogenesis theories such as stasis-heat theory and cancer toxicity theory.Based on this,the legislation of medication can improve the clinical effi-cacy,and it is realized that identifying the pathogenesis is the key link in syndrome differentiation and treatment.In his later years,Professor Zhou Zhongying,guided by the holistic view,proposed the"thirteen pathogenesis"and constructed a new system of TCM pathogenesis differentiation,highlighting the guiding value of complex pathogenesis and the causal chain of pathogenesis elements to complex clinical diseases and syndromes,forming a theory with the idea of"examining syndromes and seeking pathogenesis,activating syndrome differentiation"as its soul.This theory breaks through the rigid thinking of syndrome differentiation and treatment based on a single pathogenesis or fixed syndrome type,reconstructs the theoretical framework of TCM with the idea of holistic view,and is a major academic innovation in modern TCM.

Platelet-rich plasma (PRP) shows promise as a regenerative modality for mild-to-moderate erectile dysfunction (ED). However, its efficacy in treating severe ED remains unknown. Blood samples from 8-week-old male rats were used to prepare PRP through a two-step centrifugation procedure, followed by chitosan activation and freeze thaw cycle. A hyperhomocysteinemia (HHcy)-related ED model was established using a methionine-enriched diet, and an apomorphine (APO) test was conducted during the 4 th week. APO-negative rats were divided into two groups and were injected with PRP or saline every 2 weeks. Erectile function and histological analyses of the corpus cavernosum were performed during the 16 th week. The results revealed that erectile function was significantly impaired in rats with HHcy-related ED compared to that in age-matched rats but was improved by repeated PRP injections. Immunofluorescence staining revealed a reduction in reactive oxygen species and additional benefits on the recovery of structures within the corpus cavernosum in rats that received PRP treatment compared to those in the saline-injected control group. Therefore, PRP could enhance functional and structural recovery in a severe HHcy-related ED model. A notable strength of the present study lies in the use of a repeated intracavernous injection method, mirroring protocols used in human studies, which offers more reliable results for translating the findings to humans.
Animals ; Male ; Platelet-Rich Plasma ; Hyperhomocysteinemia/complications* ; Erectile Dysfunction/etiology* ; Rats ; Disease Models, Animal ; Penis ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism* ; Penile Erection/physiology* ; Apomorphine/administration & dosage*

The human fetal sacroiliac joint (SIJ) is characterized by unequal development of the paired bones and delayed cavitation. Thus, during the long in utero period, the bony ilium becomes adjacent to the cartilaginous sacrum. This mor phology may be analogous to that of the temporomandibular joint (TMJ). We examined horizontal histological sections of 24 fetuses at 10–30 weeks and compared the timing and sequences of joint cartilage development, cavitation, and ossification of the ilium. We also examined histological sections of the TMJ and humeroradial joint, because these also contain a disk or disk-like structure. In the ilium, endochondral ossification started in the anterior side of the SIJ, extended posteriorly and reached the joint at 12 weeks GA, and then extended over the joint at 15 weeks GA. Likewise, the joint cartilage appeared at the anterior end of the future SIJ at 12 weeks GA, and extended along the bony ilium posteriorly to cover the entire SIJ at 26 weeks GA. The cavitation started at 15 weeks GA. Therefore, joint cartilage development seemed to follow the ossification of the ilium by extending along the SIJ, and cavitation then occurred. This sequence “ossification, followed by joint cartilage formation, and then cavitation” did not occur in the TMJ or humeroradial joint. The TMJ had a periosteum-like membrane that covered the joint surface, but the humeroradial joint did not. After muscle contraction starts, it is likely that the mechanical stress from the bony ilium induces development of joint cartilage.