ObjectiveTo reveal the mechanism of Zuogui Jiangtang Jieyu prescription against damage to hippocampal synaptic microenvironment via suppressing glutamate receptor 2 （GluR2）/Parkin signal-mediated mitophagy in rats with diabetes-related depression （DD）. MethodsEighty male SD rats underwent adaptive feeding for 5 days before the study. Ten rats were randomly assigned to the normal group. The model of DD rats was established with the rest by 2-week high-fat diet + streptozotocin （STZ） tail intravenous injection + 28 days of chronic unpredictable mild stress （CUMS） combined with isolation. The rats were randomly divided into a normal group， a model group， a GluR2 blocker group （5 μg·kg^-1）， a GluR2 agonist group （10 μg·kg^-1）， a metformin + fluoxetine group （0.18 g·kg^-1 metformin + 1.8 mg·kg^-1 fluoxetine）， and high- and low-dose Zuogui Jiangtang Jieyu prescription groups （20.52 and 10.26 g·kg^-1， respectively）. The rats in the GluR2 blocker group and the GluR2 agonist group were continuously injected with CNQX and Cl-HIBO in the dentate gyrus of the hippocampus once a week starting from stress modeling， respectively， while the metformin + fluoxetine group and the high- and low-dose Zuogui Jiangtang Jieyu prescription groups were continuously given intragastric administration for 28 d at the same time of stress modeling. Depression-like behavior was evaluated by open field and forced swimming experiments. The levels of serum insulin and adenosine triphosphate （ATP） in hippocampus were detected by biochemical analysis. The levels of 5-hydroxytryptamine （5-HT） and dopamine （DA） in hippocampus were detected by enzyme-linked immunosorbent assay （ELISA）. The autophagosomes of hippocampal neurons were observed by transmission electron microscopy. The morphology and structure of dendrites and spines of hippocampal neurons were evaluated by Golgi staining. Western blot detected the expression levels of GluR2 and Parkin proteins in hippocampus. The expression levels of GluR2， Parkin， regulating synaptic membrane exocytosis protein 3 （RIMS3）， and postsynaptic density protein 95 （PSD95） in the dentate gyrus of the hippocampus were detected by immunofluorescence. ResultsCompared with the normal group， the model group exhibited reduced total activity distance in the open field and increased immobility time in forced swimming （P<0.01）， lowered levels of serum insulin and ATP， 5-HT， and DA in hippocampus （P<0.01）， increased autophagosomes of hippocampal neurons， significantly damaged morphology and structure of dendrites and spines of hippocampal neurons， decreased expression levels of GluR2， RIMS3， and PSD95 in hippocampus， and an increased Parkin expression level （P<0.05， P<0.01）. Compared with the model group， the GluR2 blocker group and the GluR2 agonist group showed aggravation and alleviation of the above abnormal changes， respectively （P<0.05， P<0.01）. The above depression-like behavior was significantly improved in the high- and low-dose Zuogui Jiangtang Jieyu prescription groups to different degrees. Specifically， the two groups saw elevated levels of serum insulin and ATP， 5-HT， and DA in hippocampus （P<0.05， P<0.01）， restrained increase in autophagosomes and damage to morphology and structure of dendrites and spines of hippocampal neurons， up-regulated protein expression levels of GluR2， RIMS3， and PSD95， and down-regulated Parkin expression level （P<0.05， P<0.01）. ConclusionZuogui Jiangtong Jieyu prescription can ameliorate the mitophagy-mediated damage to hippocampal synaptic microenvironment in DD rats， the mechanism of which might be related to the regulation of GluR2/Parkin signaling pathway.

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.

Objective:To explore the effect of Simo decoction improving the low duodenal inflammation and protecting the du-odenal mucosal barrier in rats with functional dyspepsia(FD).Methods:Sixty SD rats were randomly divided into control group(10 rats)and model group(50 rats),and the modeling rats were prepared by multivariate intervention method.After successful modeling,the modeling rats were randomly divided into model group,Simo decoction high-dose,medium-dose,low-dose group and mosapride group,with 10 rats in each group.The high-dose,medium-dose,and low-dose groups of Simo decoction were ga-vage given 5.62 g/kg,2.81 g/kg,and 1.40 g/kg,respectively,and the mosapride group was gavage given 0.305 mg/kg of mosapride,and the control group and model group were gavage given the same amount of distilled water for 14 days.The body weight of rats was observed;gastric emptying rate and small bowel propulsion rate were measured;transmission electron microscopy was used to observe the morphology of duodenal epithelial cells;ELISA detected serum levels of IL-17A and IL-22;Western blot and immunohistochemis-try were used to detect the expressions of protease-activated receptor 2(PAR-2)and tight junction protein(ZO-1,claudin-1)in the duodenum.Results:Compared with the control group,the body weight,gastric emptying rate and small intestinal propulsion rate of the model group were significantly reduced(P<0.01),transmission electron microscopy showed widening of the duodenal epithelial cell space,serum IL-17A and IL-22 levels were significantly increased(P<0.01),the expression of PAR-2 in duodenal tissue was in-creased,and the expressions of ZO-1 and claudin-1 were downregulated(P<0.01).Compared with model group,the gastric emptying rate and small intestinal propulsion rate in Simo decoction high-dose,medium-dose and mosapride group were increased(P<0.05,P<0.01),the contents of IL-17A and IL-22 in serum decreased(P<0.05,P<0.01),and the expression of PAR-2 in duodenal tissues was down-regulated,the expressions of ZO-1 and claudin-1 was significantly increased(P<0.01).The low-dose group of Simo soup could improve weight loss(P<0.01),reduce IL-17A content and PAR-2 expression,and increase ZO-1 and claudin-1 expression(P<0.05,P<0.01),while the effect on other indexes was not obvious.Conclusion:Simo decoction may reduce low-grade duodenal in-flammation to repair the mucosal barrier by down-regulating the levels of IL-17A and IL-22 and the expression of PAR-2,and up-regu-lating the expression of ZO-1 and claudin-1,so as to exert the effect of FD treatment.

Background and Purpose:Neoadjuvant immunotherapy currently significantly enhances treatment efficacy for locally advanced rectal cancer(LARC);However,clinical management of immune-related adverse events(irAEs)lacks robust evidence.This study aimed to investigate the characteristics,clinical management strategies,and outcomes of irAEs during neoadjuvant immunotherapy for rectal cancer,providing a basis for optimizing irAEs monitoring and intervention.Methods:We retrospectively analyzed clinical data from LARC patients who developed irAEs after receiving neoadjuvant immunotherapy at Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,between July 2022 and June 2024.Types of irAEs,severity,time of onset,management strategies,and outcomes were recorded.All patients underwent regular follow-up for at least 6 months.This study has been approved by Peking Union Medical College Hospital,Chinese Academy of Medical Sciences(ethical approval number:I-24PJ0024).Descriptive statistics were used to summarize irAEs patterns and management approaches.Results:A total of 41 irAE episodes occurred among the 30 patients.Mild irAEs(Grade 1-2)accounted for 78.0%(32/41),while severe irAEs(Grade 3-4)constituted 22.0%(9/41).Five patients(16.7%)permanently discontinued treatment due to severe toxicity.Endocrine toxicities were most frequent(36.6%,15/41),primarily characterized by progression from hyperthyroidism to hypothyroidism;75.0%required thyroid hormone replacement therapy.One case of delayed-onset adrenal insufficiency was alleviated with glucocorticoid(GC)therapy.Among hepatotoxicities(19.5%,8/41),62.5%were Grade 3 injury,and 37.5%required GC intervention;two patients experienced recurrence during adjuvant chemotherapy.Three cases of severe myositis occurred,accompanied by asymptomatic myocardial injury(evidenced by markedly elevated creatine kinase and concurrent changes in cardiac biomarkers),all requiring high-dose GC pulse therapy combined with intravenous immunoglobulin or immunosuppressants(recovery period:2-4 months).Nine dermatological reactions were managed with topical therapy.Two gastrointestinal events occurred,including one Grade 3 diarrhea treated with GCs.The overall GC usage rate was 31.7%(13/41),with 76.9%administered for Grade≥3 irAEs.Conclusion:irAEs during neoadjuvant immunotherapy for LARC are predominantly mild-to-moderate and manageable with supportive care.However,some patients develop severe(Grade 3-4)irAEs requiring multidisciplinary management.GC usage is concentrated in higher-grade irAEs,with severe myositis and cardiac involvement necessitating intensive immunosuppressive therapy despite their rarity.Recurrence of irAEs during adjuvant chemotherapy in a minority of patients underscores the necessity for early recognition,graded intervention,and comprehensive management throughout the entire treatment cycle.

Objective:To analyze the risk factors of in-hospital mortality in patients with femoral neck fracture and establish a prediction model for in-hospital mortality.Methods:From 2014 to 2023, a total of 4,028,102 hospitalized patients from six directly affiliated hospitals and two co-constructed affiliated hospitals of Peking University were retrospectively analyzed. Among them, 4,744 patients were hospitalized with femoral neck fractures, including 1,486 males and 3,258 females, aged 74±13.3 years (range, 19-103 years). Gender, age, length of hospital stay, hospitalization costs, preoperative comorbidities, treatment methods, anesthesia methods, and in-hospital mortality were extracted from the medical records. According to the presence or absence of in-hospital death, the patients were divided into death group and survival group. The differences in general data and clinical indicators between the two groups were compared, and the indicators with statistically significant differences were included in binary logistic regression analysis to screen the risk factors for in-hospital death in patients with femoral neck fracture. The receiver operating characteristic (ROC) curve for predicting in-hospital mortality of femoral neck fracture was drawn, and the area under the curve (AUC) was calculated.Results:There were 30 cases in the death group and 4,714 cases in the survival group, with a mortality rate of 0.63%. Among the dead patients, 20 had undergone hip replacement, and 10 had received non-surgical treatment. In the death group, age ( t=7.524, P<0.001), length of hospital stay ( t=3.802, P<0.001), hospitalisation cost ( t=3.961, P<0.001), rate of non-surgical treatment ( P<0.001), anaesthesia modality ( P=0.002), dementia ( P=0.045), malignant tumour ( P<0.001), renal insufficiency (χ 2=27.901, P<0.001), hypertension (χ 2=4.155, P=0.042), cerebral infarction (χ 2=8.271, P=0.004), urinary infections ( P=0.043), electrolyte disorders (χ 2=16.660, P<0.001), post-cholecystectomy ( P=0.070), abnormal liver function ( P=0.015), schizophrenia ( P=0.062), myocardial infarction (χ 2=19.057, P<0.001), diabetes mellitus with end-organ damage ( P=0.036), congestive heart failure (χ 2=93.122, P<0.001), and chronic obstructive pulmonary disease (χ 2=27.714, P<0.001) were greater than in the survival group, and the differences were statistically significance ( P<0.10). Bicategory logistic regression analysis showed age ( OR=1.08, P=0.008), non-surgical treatment ( OR=2.87, P=0.017), combined malignancy ( OR=9.35, P<0.001), renal insufficiency ( OR=4.07, P=0.004), hypertension ( OR=4.45, P=0.007), cerebral infarction ( OR=2.42, P=0.040), electrolyte disorders ( OR=4.29, P=0.009), schizophrenia ( OR=41.23, P=0.002), chronic obstructive pulmonary disease ( OR=3.84, P=0.002), and congestive heart failure ( OR=7.08, P<0.001) were the independent risk factors for in-hospital mortality of femoral neck fracture. The AUC and its 95% confidence interval (CI) for the predictive model were 0.908(0.84, 0.97), indicating excellent predictive value. Conclusion:Elderly, non-surgical treatment, malignant tumor, renal insufficiency, hypertension, cerebral infarction, electrolyte disturbance, schizophrenia, chronic obstructive pulmonary disease, congestive heart failure are associated with higher in-hospital mortality in patients with femoral neck fracture.

Objective:To evaluate the early outcomes of total hip arthroplasty (THA) and discuss the revisions post THA in the treatment for Kashin-Beck disease (KBD) with severe hip problems.Methods:This retrospective cohort study enrolled 50 patients (64 hips) with a mean age of 52.4±8.7 years, including 25 male patients and 25 female patients (36 left hips and 28 right hips), who were diagnosed as KBD with hip problems and received THA at Arthritis Clinical and Research Centre, Peking University People's Hospital from October 2019 to January 2024. The leg length discrepancy (LLD), femoral offset (FO), abduction angle and anteversion angle were calculated preoperatively and one week post-operation. The postoperative radiological indexes and the functional outcomes in the last follow-up were compared with the preoperative assessment.Results:The surgical duration was 105(80, 120) min and the bleeding amount was 300(200, 400) ml. All the cases were followed up for an average of 37 months (ranging from 21 to 44 months). Significant differences were found on postoperative radiological images, with LLD improving to 0.50±0.78 cm from a preoperative value of -1.36±0.79 cm, and FO increasing to 3.28±1.01 cm from 2.72±0.83 cm ( P<0.05). The mean postoperative abduction angle and anteversion angle were 42.5°±7.7° and 15.1°±5.9°, respectively. A total of 71.8% and 95.3% hips fell within the Lewinnek safe zones of abduction angle and anteversion angle, respectively. In terms of functional outcomes, the average range of motion improved significantly to 185°(173°, 210°) from a preoperative value of 99°(76°, 123°), and the Harris Hip Score increased from 35(26, 43) preoperatively to 70(63, 80) postoperatively ( P<0.05). During the follow-up, there were complications for two cases of femoral stem loosening, one case of periprosthetic femoral fracture, one case of hip dislocation, and one case of acetabular component loosening with hip subluxation. Additionally, seven patients exhibited Trendelenburg gait. A total of five hips required revision surgery due to severe complications, including two cases of femoral stem loosening, one case of periprosthetic femoral fracture, one case of hip dislocation, and one case of acetabular component loosening with subluxation. Conclusions:Patients with KBD demonstrated significant early improvements in both radiological and functional outcomes following THA.

Objective:The aim was to analyze key indicators for the diagnosis and treatment of chronic hepatitis B（CHB），including virus detection rate，standardized treatment rate，and loss to follow-up rate，in order to provide a basis for optimizing diagnosis and treatment plans，improve the diagnosis and treatment level of CHB，and improve patient prognosis.Methods:Patients with CHB admitted to the Guangzhou Eighth People′s Hospital Affiliated to Guangzhou Medical University from January 2024 to January 2025 were enrolled. The datas were collected and organized using Excel. Statistical analysis was conducted using SPSS 26.0 software，with a focus on evaluating core indicators such as virus detection rate，standardized treatment rate，and loss to follow-up rate.Results:The positive rate of hepatitis B surface antigen（HBsAg）in non-specific patients was 28.95%，the antiviral treatment rate in specialized patients was 90.78%，and the standardized antiviral drug conversion treatment rate in low-level viremia（LLV）patients was 61.45%. The standardized antiviral drug conversion treatment rates for high-risk patients with combined kidney/bone injuries were 72.75% and 74.40%，respectively. The overall dropout rate was 10.47%，with a dropout rate of 13.80% for LLV patients.Conclusions:The antiviral treatment coverage rates in CHB patients were over 90%，but in certain groups（such as LLV patients and those with kidney or bone injuries），the standardized treatment rates were still low and loss to follow-up rates were high，suggesting the need to improve HBV screening，treatment for special populations，and patient adherence.

Objective To observe the effect of Sishen Pills on the expression of TREK-1 signaling pathway in rats of irritable bowel syndrome with diarrhea(IBS-D);To explore its mechanism in treating IBS-D.Methods Ten SPF-grade SD rats were randomly selected as the normal group,and the remaining 30 rats were used to prepare the IBS-D rat model by senna gavage combined with water stress avoidance method,and then the modeled rats were randomly divided into the model group,Western medicine group(15.23 mg/kg pivoxyl bromide)and Chinese medicine group(7.32 g/kg Sishen Pills).The medication groups were gavaged by corresponding drugs,and the normal group and model group were given equal volume of pure water,once a day,for consecutive 14 d.The general state of the rats was observed,the contents of serum cyclic adenosine monophosphate(cAMP),protein kinase A(PKA)and phosphorylated extracellular signal-regulated kinase(p-ERK)were detected by ELISA,the positive expressions of biportal potassium channel TREK-1 and p-ERK in colonic tissue were detected by immunofluorescence,the expressions of cAMP,PKA and p-ERK protein were detected by Western blot.Results Compared with the normal group,the body mass of rats in the model group was significantly reduced,and loose stool rate significantly increased(P<0.01);the contents of cAMP,PKA and p-ERK in serum were significantly increased(P<0.05,P<0.01);the positive expression and protein expression of TREK-1 in colonic tissue were significantly reduced,while the positive expression of p-ERK significantly increased(P<0.01),and the expressions of cAMP and PKA proteins significantly increased(P<0.01).Compared with the model group,the body mass of rats in Chinese medince group significantly increased,and loose stool rate significantly decreased(P<0.01);the contents of cAMP,PKA and p-ERK in serum were significantly reduced(P<0.05,P<0.01);the positive expression and protein expression of TREK-1 in colonic tissue significantly increased(P<0.01),while the positive expression of p-ERK significantly decreased(P<0.05),and the expressions of cAMP and PKA proteins significantly decreased(P<0.01).Conclusion Sishen Pills may regulate intestinal motility by affecting the expression of the TREK-1 signaling pathway,thereby treating IBS-D.

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*