[Objective] To evaluate the clinical application value of intrauterine perfusion with platelet-rich plasma (PRP) combined with in vitro fertilization-frozen-thawed embryo transfer (IVF-FET) in patients with chronic endometritis (CE). [Methods] A randomized controlled trial (RCT) was conducted, enrolling 60 CE patients undergoing artificial cycle frozen embryo transfer at our hospital from January 2022 to January 2024. Participants were randomly divided into three groups: Group A (routine frozen embryo transfer, n=20), Group B (routine frozen embryo transfer + one PRP intrauterine perfusion, n=20), and Group C (routine frozen embryo transfer + two PRP intrauterine perfusions, n=20). Endometrial thickness during the transformation and transplantation phases, uterine artery pulsatility index (PI), resistance index (RI), systolic peak velocity/end-diastolic velocity (S/D) ratio during transplantation, serum levels of IL-2, IL-4, IL-6, IL-10, and TNF-α during transplantation, as well as biochemical pregnancy rate, clinical pregnancy rate, live birth rate, and early miscarriage rate were compared across groups. [Results] No significant differences in endometrial thickness were observed among the three groups during the transformation phase (P>0.05). During the transplantation phase, endometrial thickness in Groups C and B was significantly higher than in Group A[9.54 (8.96-10.22) and 8.90 (8.34-9.72) vs 8.37 (7.89-8.75) mm, P<0.05], with Group C showing greater thickness than Group B (Z=3.733, P<0.05). Endometrial thickness in Groups C and B during transplantation was significantly increased compared to their respective transformation phases (Z=2.191, 2.462; P<0.05). Groups C and B exhibited lower PI, RI, and S/D values than Group A[PI:1.87 (1.77-1.97), 1.94 (1.88-2.15) vs 2.43 (2.35-2.49); RI:0.75 (0.73-0.77), 0.78 (0.75-0.81) vs 0.84 (0.83-0.86); S/D:2.61 (2.33-3.42), 3.01 (2.20-3.93) vs 3.72 (3.06-4.49); P<0.05]. Group C demonstrated lower PI and RI than Group B (P<0.05). IL-2 levels in Groups C and B were higher than in Group A[3.88 (2.71-5.01), 3.59 (2.73-4.38) vs 3.16 (2.11-3.25) ng/L, P<0.05], while IL-4, IL-6, IL-10, and TNF-α levels were significantly lower (IL-4: Z=1.428, 2.421; IL-6: Z=1.754, 2.435; IL-10: Z=1.754, 2.854; TNF-α: Z=1.961, 1.765; P<0.05). Group C had lower IL-6 levels than Group B (Z=3.976, P<0.05). Biochemical pregnancy rate, clinical pregnancy rate, and live birth rate in Group C were significantly higher than in Group A (75% vs 40%, 70% vs 35%, 60% vs 20%, P<0.05). No significant differences in early miscarriage rates were observed among the groups (χ²=3.750, P>0.05). [Conclusion] Intrauterine autologous PRP perfusion in CE patients enhances pregnancy and live birth rates, improves pregnancy outcomes post-FET, and demonstrates superior efficacy in endometrial repair and receptivity with two PRP perfusions compared to a single perfusion. This provides a safe and effective therapeutic option for optimizing outcomes in CE patients with prior implantation failure.

With the rapid advancement of artificial intelligence technology, chatbots have shown great potential in the healthcare sector. From personalized health advice to chronic disease management and psychological support, chatbots have demonstrated significant advantages in improving the efficiency and quality of healthcare services. As the scope of their applications expands, the relationship between technological complexity and practical application scenarios has become increasingly intertwined, necessitating a more comprehensive evaluation of both aspects. This paper, from the perspective of he althcare applications, systematically reviews the technological pathways and development of chatbots in the medical field, providing an in-depth analysis of their performance across various medical scenarios. It thoroughly examines the advantages and limitations of chatbots, aiming to offer theoretical support for future research and propose feasible recommendations for the broader adoption of chatbot technologies in healthcare.

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells' large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.

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*

BackgroundNon-suicidal self-injury （NSSI） behaviors have become a serious global public health issue.The detection rate of NSSI behaviors among college students in China ranges from 9.8% to 13.53%. Integrated theoretical models suggest that distal family risk factors influence NSSI behaviors through emotional regulation mechanisms. However， existing researches have predominantly focused on single family risks， leaving the relationship between cumulative family risks and NSSI behaviors， as well as the underlying pathways， remain unclear. ObjectiveTo explore the effects of cumulative family risk on NSSI behaviors among college students， analyze the chain mediating roles of emotional regulation difficulties and depression， and examine the moderating effect of gender， so as to provide references for targeted interventions for NSSI behaviors in college students. MethodsOn March 1， 2024， a cluster sampling method was employed to select 518 college students from two universities in Heilongjiang Province. Assessments were conducted using Chinese version of the Childhood Trauma Questionnaire （CTQ）， the Difficulties in Emotion Regulation Scale （DERS）， the Patient Health Questionnaire Depression Scale-9 item （PHQ-9） and the Adolescent Self-Injury Questionnaire. Logistic regression analysis was used to examine the impact of cumulative family risk factors on NSSI behaviors among college students. Model 6 in Process 4.1 was applied to test the chain mediating roles of emotional regulation difficulties and depression in the relationship between cumulative family risk and NSSI behaviors， while model 83 was utilized to analyze the moderating effects of gender on the path "cumulative family risk → emotion regulation difficulties". ResultsA total of 475 （91.70%） college students completed valid questionnaires. Logistic regression analysis revealed that childhood abuse （OR=2.561， 95% CI： 1.566-2.561）， non-parental family structure （OR=2.108， 95% CI：1.102-4.029） and left-behind experience （OR=2.356， 95% CI： 1.021-5.439） were risk factors for NSSI behaviors among college students. Cumulative family risk positively predicted NSSI behaviors （β=0.345，95% CI：1.059-4.286， P<0.01）， and this relationship was mediated by a chain pathway involving emotional regulation difficulties （β=0.136，95% CI： 0.882-4.681， P<0.05） and depression （β=0.160， 95% CI： 0.316-1.073， P<0.01）. Gender moderated the relationship between cumulative family risk and emotional regulation difficulties （β=0.103， 95% CI： 1.567-8.316， P<0.01）， with cumulative family risk significantly predicting emotional regulation difficulties in female students （β=0.374， 95% CI： 0.099-0.084， P<0.01）. ConclusionCumulative family risk can directly influence college students' NSSI behaviors， and may also indirectly affect NSSI behaviors through the mediating roles of emotional regulation difficulties and depression. The path "cumulative family risk → emotional regulation difficulties" in this mediating model is moderated by gender.［Funded by Heilongjiang Philosophy and Social Sciences Research Planning Project （number， 24SHB007）］

Sishen Pills is a classic prescription for the treatment of spleen and kidney diarrhea,which has the effect of warming the kidney and the spleen,astringent intestine and antidiarrheal.In modern clinical application,the modified prescriptions based on Sishen Pills,combined with other treatments of TCM and integrated traditional Chinese and Western medicine are often used to treat ulcerative colitis with spleen-kidney yang deficiency syndrome,and the curative effect is remarkable.Experimental pharmacological studies have shown that Sishen Pills may achieve the purpose of ulcerative colitis by regulating the expression of related signaling pathway proteins,regulating inflammatory factors,inhibiting inflammatory response,regulating autophagy,regulating intestinal flora,improving intestinal mucosal permeability,repairing intestinal mucosal barrier,regulating cellular energy metabolism,anti-oxidative stress,regulating cellular immune function,etc.In this article,the research status of Sishen Pills in the treatment of ulcerative colitis was sorted out and summarized,in order to provide reference for further study of its mechanism and clinical application.

To evaluate the correlation between ultrasound ossification ratio(OR) and exercise intensity among adolescents.

Objective:Farfarae Flos has the effect of cough suppression and phlegm elimination,with cough suppression as the main function.Studies have revealed that certain components of Farfarae Flos may be related to its cough suppressant effect,and some components have been confirmed to have cough suppressant activity.However,the antitussive material basis of Farfarae Flos has not been systematically elucidated.This study aims to elucidate the group of active ingredients in Farfarae Flos with cough suppressant activity by correlating the high performance liquid chromatography(HPLC)fingerprint of Farfarae Flos extract with its cough suppressant activity. Methods:HPLC was used to establish the fingerprint profiles of 10 batches of Farfarae Flos extract and obtain their chemical composition data.Guinea pigs were selected as experimental animals and the citric acid-induced cough model was used to evaluate the antitussive efficacy data of 10 batches of Farfarae Flos extract.SPF-grade healthy male Hartley guinea pigs were randomly divided into the S1 to S10 groups,a positive control group,and a blank control group(12 groups in total),with 10 guinea pigs in each group.The S1 to S10 groups were respectively administered Farfarae Flos extract S1 to S10(4 g/kg),the positive control group was administered pentoverine citrate(10 mg/kg),and the blank control group was administered purified water.Each group received continuous oral administration for 5 days.The guinea pigs were placed in 5 L closed wide-mouth bottles,and 17.5%citric acid was sprayed into the bottle with an ultrasonic atomizer at the maximum spray intensity for 0.5 minutes.The cough latency period and cough frequency in 5 minutes were recorded for each guinea pig.Grey relational analysis(GRA)and partial least squares regression(PLSR)were used to conduct spectral-effect correlation analysis of the chemical composition data of Farfarae Flos extract and the antitussive efficacy data,and predict the group of active ingredients in Farfarae Flos with antitussive activity.The bioequivalence verification was conducted to verify the predicted group of active ingredients in Farfarae Flos with antitussive activity:SPF-grade healthy male Hartley guinea pigs were randomly divided into a S9 group,an active ingredient group,a positive control group,and a blank control group(4 groups in total),with 10 guinea pigs in each group.The S9 group was administered Farfarae Flos extract S9(4 g/kg),the active ingredient group was administered the predicted combination of antitussive active ingredients(dose equivalent to 4 g/kg of Farfarae Flos extract S9),the positive control group was administered pentoverine citrate(10 mg/kg),and the blank control group was administered purified water.Each group received continuous oral administration for 5 days,and animal modeling and observation of efficacy indicators were the same as above. Results:The HPLC fingerprint of 10 batches of Farfarae Flos extract was established,and the peak area data of 14 main common peaks were obtained.The antitussive effect data of 10 batches of Farfarae Flos extract were obtained.Compared with the blank control group,the cough latence in the positive control group and S1,S2,S3,S4,S6,S7,S8,S9,S10 groups was prolonged(all P<0.01),while the cough frequency in 5 minutes in the positive control group and S1,S2,S4,S6,S8,S9,S10 groups was decreased(all P<0.05).The analysis of spectrum-effect relationship revealed that isochlorogenic acid C,isochlorogenic acid A,chlorogenic acid,isochlorogenic acid B,isoquercitrin,and rutin had high contribution to the antitussive effect of Farfarae Flos,and the 6 components were predicted to be the antitussive component group of Farfarae Flos.The verification of bioequivalence showed that there were no statistically significant differences in the antitussive effect between the S9 group and the antitussive component composition group(all P>0.05),which confirmed that isochlorogenic acid C,isochlorogenic acid A,chlorogenic acid,isochlorogenic acid B,isoquercetin,and rutin were the antitussive component group of Farfarae Flos. Conclusion:The analysis of spectrum-effect relationship combined with the verification of bioequivalence could be used to study the antitussive material basis of Farfarae Flos.The antitussive effect of Farfarae Flos is the result of the joint action of many components.

Purpose: Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus. Methods: p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts. Results: p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells. Conclusion Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.