Nano liquid chromatography-high resolution tandem mass spectrometry(LC-HRMS/MS)is widely used for body fluid peptidome analysis,yet the impact of replicate analyses remains overlooked.Using salivary peptidome,in this work,10 replicate analyses of the same sample were conducted.It was found that although m/z and molecular weight ranges were consistent across replicates,single runs identified only 348-576 unique peptides from 32-39 degraded proteins.Merging all replicates revealed 1237 peptides from 77 proteins,a 2.5 folds increase in peptides and 2 folds increase in proteins.Instrument stability was confirmed via intensity/retention time of 12 peptides.Merged peptides primarily derived from high-abundance proteins(e.g.,Statherin,PRP1/2).Analysis of 20 peptides showed that the some peptides were detected in single analysis but confidence varying(19%-99%),low-confidence peptides(<95%)exceeded 95%after replicate.signal intensity alone didn't determine confidence and peptides spanning the sequence region between the longest and the shortest detected fragments could be identified.The above findings suggested that single-run LC-MS peptidomics analysis carried inherent false negatives and uncertainties.However,by integrating the results of a single analysis with the mechanism of enzymatic hydrolysis for endogenous peptides,it was possible to make reasonable inferences and extrapolations regarding peptides derived from highly abundant degraded proteins.

Objective To investigate the relationship between internet addiction and SIOSS score,and to examine the mediating role of impulsivity and the moderating role of mental health level.Methods A total of 393 college students were tested with internet addiction scale,Barratt impulsiveness scale-version 11,SIOSS and symptom checklist 90 to establish a moderated mediation model.Results After adjusted for age,internet addiction tendency had a positive predictive effect on SIOSS score(β=0.523,P＜0.01).Impulsivity played a partial mediating role in the relationship between internet addiction and SIOSS score,with a mediating effect value of 0.087(45.72％).The first half of the mediating effect of internet addiction→impulsivity→SIOSS score was moderated by mental health level(β=-0.118,P＜0.001).The predictive effect of internet addiction on impulsivity was stronger in individuals with good mental health level(with the indirect effect value of 0.619 9+0.048 7)compared with the individuals with poor mental health level(with the indirect effect value of 0.439 5+0.048 5).Conclusion Internet addiction can increase SIOSS score by enhancing individual impulsivity,but this effect is more pronounced in individuals with good mental health and then affect SIOSS score.

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: Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA. METHODS: Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment. RESULTS: Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex. CONCLUSION EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects. Please cite this article as: Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 2025; 23(2): 159-168.
Animals ; Electroacupuncture ; Male ; Magnetic Resonance Imaging ; Depression/diagnostic imaging* ; Mice, Inbred C57BL ; Brain/diagnostic imaging* ; Disease Models, Animal ; Mice ; Pain/diagnostic imaging* ; Acupuncture Points

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective:To explore the safety of laparoscopic modified transcystic biliary drainage(modified C-tube technique)in the treatment of biliary stones and application of diagnosing biliary disease.Methods:A retrospective analysis was conducted on the clinical data of 68 cases of biliary stones successfully treated with laparoscopic modified C-tube technique from August 2021 to December 2023.The safety,effectiveness,and area of applications were analyzed.The reliability of the principle of the modified fixation method was verified by using an ex vivo gallbladder.Results:Three cases of ex vivo gallbladder demonstrated that the strength of the modified fixation method was reliable,and the sinus tract formed by suture after immediate extraction of the C tube could be dislocated and closed,resisting the bile outflow caused by the weight of the gallbladder.Among the 68 patients,42 were difficult biliary stones,6 were suspected common bile duct stones,and 5 were extrahepatic bile duct stones combined with intrahepatic bile duct stones.Among them,48 cases underwent choledochoscopy assisted trans-choledochal approach for stone removal,and 10 cases underwent transcystic approach stone removal,Six patients underwent simply basket exploration and removal of stones through the cystic duct(5 patients had no residual stones on postoperative C-tube angiography,1 patient had suspected residual stones,and the patient refused further examination and treatment for no symptom),and 4 patients only underwent biliary drainage through the cystic duct;two patients with retained stone passed after the use of topical nitrate drip infusion via C-tube,seven cases underwent endoscopic retrograde cholangiopancreatography(ERCP),stone removal with the assistance of a C-tube after laparoscopic surgery,and the results were uneventful.The mean surgical time was(131±44)min(76-279 min),the maximum daily drainage volume of the C-tube was(401±235)mL/d(10-1 150 mL/d),the hospital stay was(8.6±3.6)d(2-19 d),and the mean time of C-tube removal was(11±6.9)d(5-46 d).There were 14 overall complications,including 2 residual stones,and 12 C-tube related complications,comprising of 1 gradeⅢ a,2 grade Ⅱ,and 9 grade Ⅰ.There were 9 cases of C-tube related adverse events that did not cause complications,including 3 of early detachment,2 of displacement,and 4 of deep insertion.The median follow-up time after surgery was 21(2-30)months,and 5 patients had recurrent stones.Among them,4 patients had slow contrast outflow during cholangiogram,and 1 patient had obvious pancreaticobiliary reflux.55 patients underwent C-tube amylase measurement,and 9 cases showed a significant increase in bile amylase(349-44 936 U/L),suggesting the presence of pancreaticobiliary reflux.Conclusion:Laparoscopic modified C-tube technique can be effectively used in the treatment of biliary stones,which is relatively safe and can be attempted in the diagnosis of biliary diseases.

Objective:To identify the factors influencing the diagnostic accuracy of endoscopic ultrasonography (EUS) for colorectal submucosal tumors (SMT).Methods:A retrospective analysis was conducted on 330 colorectal SMT lesions (from 323 patients) diagnosed by EUS at Shenzhen Hospital of Southern Medical University from December 2015 to October 2023. Pathological diagnosis were confirmed through endoscopic resection, EUS-guided fine needle aspiration (EUS-FNA) or surgical resection. Diagnostic accuracy was calculated for each type of colorectal SMT. Univariate and multivariate logistic regression analysis were performed to identify factors affecting EUS diagnostic accuracy.Results:The overall diagnostic accuracy of EUS for colorectal SMT was 73.6% (243/330). Among 19 SMT subtypes enrolled, neuroendocrine neoplasms (51.2%, 169/330) and lipomas (15.5%, 51/330) were most prevalent, while 17 rare subtypes each accounted for <6%. Seven rare SMT (mucosal chronic inflammation, colorectal schwannoma, xanthogranulomatous inflammation, capillary hemangioma, colonic xanthoma, lymphadenoid complex, and angiomyolipoma) showed 0% diagnostic accuracy. Seven other subtypes (granular cell tumor, leiomyoma, rectal tonsil, intestinal schistosomiasis, fibrous tissue hyperplasia, gastrointestinal stromal tumor, and lymphangioma) showed accuracy <30%, whereas five subtypes (cyst, bowel endometriosis, neuroendocrine neoplasm, lipoma, and pneumatosis cystoides intestinalis) achieved >60% accuracy. Multivariate logistic regression analysis confirmed that the lesion location (left colon VS rectum: OR=0.06, 95% CI: 0.02-0.17, P<0.001; right colon VS rectum: OR=0.04, 95% CI: 0.01-0.13, P<0.001; ileocecal valve VS rectum: OR=0.09, 95% CI: 0.02-0.42, P=0.002); echogenicity (anechoic VS hypoechoic: OR=6.26, 95% CI: 1.31-29.97, P=0.022; hyperechoic VS hypoechoic: OR=13.39, 95% CI: 4.16-43.09, P<0.001) and ultrasonic layer (layer 4 VS layer 3: OR=0.22, 95% CI: 0.06-0.81, P=0.023) were independent influencing factors of EUS diagnostic accuracy for colorectal SMT. Conclusion:Neuroendocrine neoplasms and lipomas represent the most common colorectal SMT, whereas rare and uncommon SMT exhibit low EUS diagnostic accuracy. Lesion location, echogenicity, and ultrasonic layer significantly influence EUS diagnostic accuracy for colorectal SMT.

Objective:To explore the safety of laparoscopic modified transcystic biliary drainage(modified C-tube technique)in the treatment of biliary stones and application of diagnosing biliary disease.Methods:A retrospective analysis was conducted on the clinical data of 68 cases of biliary stones successfully treated with laparoscopic modified C-tube technique from August 2021 to December 2023.The safety,effectiveness,and area of applications were analyzed.The reliability of the principle of the modified fixation method was verified by using an ex vivo gallbladder.Results:Three cases of ex vivo gallbladder demonstrated that the strength of the modified fixation method was reliable,and the sinus tract formed by suture after immediate extraction of the C tube could be dislocated and closed,resisting the bile outflow caused by the weight of the gallbladder.Among the 68 patients,42 were difficult biliary stones,6 were suspected common bile duct stones,and 5 were extrahepatic bile duct stones combined with intrahepatic bile duct stones.Among them,48 cases underwent choledochoscopy assisted trans-choledochal approach for stone removal,and 10 cases underwent transcystic approach stone removal,Six patients underwent simply basket exploration and removal of stones through the cystic duct(5 patients had no residual stones on postoperative C-tube angiography,1 patient had suspected residual stones,and the patient refused further examination and treatment for no symptom),and 4 patients only underwent biliary drainage through the cystic duct;two patients with retained stone passed after the use of topical nitrate drip infusion via C-tube,seven cases underwent endoscopic retrograde cholangiopancreatography(ERCP),stone removal with the assistance of a C-tube after laparoscopic surgery,and the results were uneventful.The mean surgical time was(131±44)min(76-279 min),the maximum daily drainage volume of the C-tube was(401±235)mL/d(10-1 150 mL/d),the hospital stay was(8.6±3.6)d(2-19 d),and the mean time of C-tube removal was(11±6.9)d(5-46 d).There were 14 overall complications,including 2 residual stones,and 12 C-tube related complications,comprising of 1 gradeⅢ a,2 grade Ⅱ,and 9 grade Ⅰ.There were 9 cases of C-tube related adverse events that did not cause complications,including 3 of early detachment,2 of displacement,and 4 of deep insertion.The median follow-up time after surgery was 21(2-30)months,and 5 patients had recurrent stones.Among them,4 patients had slow contrast outflow during cholangiogram,and 1 patient had obvious pancreaticobiliary reflux.55 patients underwent C-tube amylase measurement,and 9 cases showed a significant increase in bile amylase(349-44 936 U/L),suggesting the presence of pancreaticobiliary reflux.Conclusion:Laparoscopic modified C-tube technique can be effectively used in the treatment of biliary stones,which is relatively safe and can be attempted in the diagnosis of biliary diseases.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.