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.

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*

Objective To explore the mechanism of protective effect of Jianpi Yichang Powder on intestinal mucosa by observing its effect on the expression of autophagy-related molecules in colon of ulcerative colitis(UC)model rats.Methods SD rats were randomly divided into normal group,model group,Jianpi Yichang Powder group and sulfasalazine group.UC rat model was established by 2,4,6-trinitrobenzene sulfonic acid/ethanol solution.After the model was successfully reproduced,the rats were given drugs orally once a day for 14 days.The general condition of rats was observed and the disease activity index(DAI)score was calculated.The pathological morphology of colonic tissue in all groups was observed by hematoxylin eosin(HE)staining.Autophagy of colonic epithelial cells was examined by transmission electron microscope.The expressions of myosin-like BCL2 interacting protein(Beclin1)and microtubule-associated protein 1 light chain 3(LC3)in colonic tissue were detected by immunofluorescence staining and Western Blot.The mRNA expressions of autophagy protein 5(Atg5),autophagy protein 7(Atg7)and ubiquitin-binding protein 62(p62)were detected by real-time quantitative polymerase chain reaction(Real-time PCR).Results Compared with the normal group,the general situation of the model group was worse,and the DAI score increased significantly(P<0.000 1).There was obvious epithelial cell damage in colonic tissue,and the number of autophagosomes decreased obviously under electron microscope.The expressions of Beclin1 and LC3-Ⅱ/LC3-Ⅰ protein as well as Atg5 and Atg7 mRNA in colonic tissue decreased significantly(P<0.000 1),while the expression of p62 mRNA increased significantly(P<0.000 1).Compared with the model group,the general condition of rats in Jianpi Yichang Powder group had recovered significantly,and the DAI score decreased significantly(P<0.000 1).Pathological damage of colonic tissue has been improved in different degrees,and the number of autophagosomes increased significantly under electron microscope.The expressions of Beclin1 and LC3-Ⅱ/LC3-Ⅰ protein as well as Atg5 and Atg7 mRNA in colonic tissue were significantly increased(P<0.01,P<0.001,P<0.000 1),while the expression of p62 mRNA was significantly decreased(P<0.01).Conclusion Jianpi Yichang Powder can protect UC colon mucosa from injury by up-regulating the expression of autophagy-related molecules including Beclin1,LC3,Atg5 and Atg7,down-regulating the expression of p62 and enhancing autophagy.

To analyze the current quality of treatment for hospitalized cancer patients in Beijing, identify major issues in treatment practices, and propose improvements.

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.

Objective:To investigate the clinical characteristics of brain metastases after radical surgery for locally advanced rectal cancer (LARC).Methods:The clinical characteristics of LARC with brain metastases treated in the Department of General Surgery, Peking Union Medical College Hospital from 2013 to 2023 were retrospectively analyzed. The inclusion criteria were rectal adenocarcinoma within 15 cm of the anal verge and having undergone radical surgery, and the exclusion criterion was primary malignant tumor of the brain. The main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific overall survival (determined as the interval between occurrence of brain metastasis to death from any causes). The Kaplan–Meier method was used for survival analysis.Results:We identified 4500 patients with LARC, 20 (0.4%) of whom had brain metastases. The mean age of patients with brain metastases was 63.8±9.3 years. They comprised five women and 15 men. The brain was the first site of metastasis in four patients (20%) whereas 18 patients had heterochronous extracranial metastases before brain metastasis. Two patients also had multi-organ metastases. The most common manifestations of brain metastases were dizziness and headache (five patients, 25%), sudden onset of limb weakness (four, 20%), sudden speech impairment (two, 10%), and polyopia (two, 10%). The metastases were diagnosed during follow-up in three patients (15%). Four of the patients were asymptomatic (20%). Treatment approaches included surgical resection (six patients, 30%), chemoradiotherapy (nine, 45%), and palliative (five, 25%). The median follow-up time was 45.5 (4–112) months until October 2023. 1y-OS, 3y-OS, and 5y-OS were 95.0%, 62.9%, and 43.3%, respectively. 1y-DFS, 3y-DFS, and 5y-DFS were 55.0%, 25.0%, and 5.0%, respectively. With brain metastasis as the starting point, the median duration of survival was 16 (10.2–21.8) months.Conclusion:The incidence of brain metastasis is relatively low in patients with LARC, who often have multiple synchronous extracranial metastases. Brain metastases lack specific manifestations and more often occur in male patients. Surgical intervention or combined radiotherapy and chemotherapy may improve disease-specific survival to a certain extent. However, the overall prognosis remains poor.

Objective:To investigate the clinical characteristics of brain metastases after radical surgery for locally advanced rectal cancer (LARC).Methods:The clinical characteristics of LARC with brain metastases treated in the Department of General Surgery, Peking Union Medical College Hospital from 2013 to 2023 were retrospectively analyzed. The inclusion criteria were rectal adenocarcinoma within 15 cm of the anal verge and having undergone radical surgery, and the exclusion criterion was primary malignant tumor of the brain. The main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific overall survival (determined as the interval between occurrence of brain metastasis to death from any causes). The Kaplan–Meier method was used for survival analysis.Results:We identified 4500 patients with LARC, 20 (0.4%) of whom had brain metastases. The mean age of patients with brain metastases was 63.8±9.3 years. They comprised five women and 15 men. The brain was the first site of metastasis in four patients (20%) whereas 18 patients had heterochronous extracranial metastases before brain metastasis. Two patients also had multi-organ metastases. The most common manifestations of brain metastases were dizziness and headache (five patients, 25%), sudden onset of limb weakness (four, 20%), sudden speech impairment (two, 10%), and polyopia (two, 10%). The metastases were diagnosed during follow-up in three patients (15%). Four of the patients were asymptomatic (20%). Treatment approaches included surgical resection (six patients, 30%), chemoradiotherapy (nine, 45%), and palliative (five, 25%). The median follow-up time was 45.5 (4–112) months until October 2023. 1y-OS, 3y-OS, and 5y-OS were 95.0%, 62.9%, and 43.3%, respectively. 1y-DFS, 3y-DFS, and 5y-DFS were 55.0%, 25.0%, and 5.0%, respectively. With brain metastasis as the starting point, the median duration of survival was 16 (10.2–21.8) months.Conclusion:The incidence of brain metastasis is relatively low in patients with LARC, who often have multiple synchronous extracranial metastases. Brain metastases lack specific manifestations and more often occur in male patients. Surgical intervention or combined radiotherapy and chemotherapy may improve disease-specific survival to a certain extent. However, the overall prognosis remains poor.

Objective To investigate the mediating role of medical coping strategies in the relationship between perceived social support and resilience among patients with occupational pneumoconiosis (hereinafter referred to as pneumoconiosis). Methods A total of 240 pneumoconiosis patients were selected as the study subjects using the convenience sampling method. The Perceived Social Support Scale, the 10-item Connor-Davidson Resilience Scale and Medical Coping Strategies Questionnaire were used to evaluate their perceived social support, resilience and medical coping strategies. AMOS 26.0 software was used to construct the structural equation model. Results The average scores of perceived social support and resilience were (56.6±0.9) and (20.9±7.5), respectively. The scores for the dimensions of confrontation, avoidance and resignation of medical coping strategies were (20.2±3.6), (11.2±3.1) and (18.1±2.9), respectively. The score of resilience was positively correlated with the score of perceived social support, avoidance dimension and confrontation dimension of medical coping strategies (r=0.260, 0.176, 0.174, all P<0.01). It was negatively correlated with resignation coping (r=-0.292, P<0.01). The results of mediating effect test showed that the total effect of perceived social support on resilience was 0.252 [95% confidence interval (CI) was 0.056-0.448], which mainly affected the resilience by affecting the resignation coping (95%CI: -0.458 to -0.104), with the indirect effect value of 0.120, accounting for 47.6% of the total effect. Conclusion The resilience of pneumoconiosis patients is moderately low. Resignation coping in medical coping strategies plays a mediating role between perceived social support and resilience in pneumoconiosis patients.