Endothelial dysfunction is one of the early triggers of vascular remodeling during pulmonary hypertension (PH) with complex predisposing mechanisms, mainly via an unbalanced generation of vasoactive factors, increased expression of growth factors, prothrombotic elements, and inflammatory markers. Conventional treatment regimens are restricted to a single therapeutic pathway, which usually leads to limited clinical outcomes. Combination therapies targeting multiple cells and several signaling pathways are increasingly adopted in PH treatment. Herein, inspired by the cocrystal pleomorphism theory, we prepared rod-shaped nanococrystals of the endothelin-1 (ET-1) receptor antagonist (bosentan, BST) and the anti-inflammatory drug (andrographolide, AG) for targeting the pulmonary endothelium and alleviating PH. The 525 nm-sized co-delivery system displayed a rod-like morphology, preferentially accumulated in the pulmonary endothelium and alleviated pulmonary artery (PA) remodeling. A three-week treatment with the preparation significantly alleviated the monocrotaline (MCT)- or Sugen 5416/hypoxia (SuHx)-induced PH by reducing the pulmonary artery pressure, increasing the survival rate, improving the hemodynamics, and inhibiting vascular remodeling. Mechanistically, the nanococrystals collaboratively repaired endothelial dysfunction by suppressing the pathways of ET-1/NF-κB/ICAM-1/TNF-α/IL-6. In conclusion, the cocrystal-based strategy offers a promising approach for constructing co-delivery systems. The developed rod-shaped nanococrystals effectively target the pulmonary endothelium and relieve experimental PH.

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

AIM To study the chemical constituents from the stems and barks of Maytenus variabilis(Hemsl.)C.Y.Cheng.METHODS The 95％ethanol extract from the stems and barks of M.variabilis was isolated and purified by silica gel,Sephadex LH-20 and semi preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Twenty-three compounds were isolated and identified as β-amyrin(1),3β-acetoxyolean-12-en-11-one(2),ursa-12-ene-11-one-3-ol octocosate(3),friedelin(4),canophyllol(5),pinoresinol(6),medioresinol(7),isolariciresinol(8),dihydrodehydrodiconiferyl alcohol(9),vanillic acid(10),7R,8S-5-methoxydihydrodehydroconiferyl alcohol(11),β-hydroxypropiovanillone(12),triptregeline B(13),triptregeline E(14),(+)-evofolin B(15),2,5-dimethoxybenzoquinone(16),olean-12-ene-3,11-dione(17),β-sitosterol(18),(-)-(7R,7'R,7"S,8S,8'S,8"S)-4',4"-dihydroxy-3,3',3",5-tetramethoxy-7,9',7',9-diepoxy-4,8"-oxy-8,8'-sesquineolignan-7",9"-diol(19),phyllostadimer B(20),rayalinol(21),lyoniresinol(22),dihydrobuddlenol B(23).CONCLUSION Compounds 3,9-11,13-14,16,19-21,23 are isolated from genus Maytenus for the first time,and compounds 2,4-5,7-8,12,15,17,22 are first found from this plant.

AIM To study the chemical constituents of Anaphalis margaritacea(L.)Benth.& Hook.f.and their antioxidant activities.METHODS Separation and purification were performed using silica gel,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antioxidant activity was determined by DPPH method and ABTS method.RESULTS Twenty-three compounds were isolated and identified as trans-tilidroside(1),4'-hydroxydehydrokawain(2),apigenin(3),3-O-kaempferol-3-O-acetyl-6-O-(p-coumamoyl)-α-D-glucopyranoside(4),kaempferol(5),quercetin-3-O-β-D-(6-O-Z-p-coumamoyl)-glucopyranoside(6),tiliroside(7),kaempferol-3-O-β-D-glucoside(8),3,5-dihydroxy-7,8-dimethoxyflavone(9),bis(2-ethylhexyl)adipate(10),3,5-dihydroxy-6,7,8-trimethoxyflavone(11),stigmasterol(12),myriophylloside B(13),1-hexadecanol(14),chlorogenic acid(15),4-hydroxy-N-{ 4-[3-(4-hydroxyphenyl)-E-acryloylamino]-butyl}-benzamide(16),3,6-dimethylpiperazine-2,5-dione(17),β-adenosine(18),5,6-dehydrokawain(19),kaempferol-3-O-(2",6"-di-O-E-p-coumaroyl)-β-D-glucopyranoside(20),kaempferol-3-O-(3"-O-E-p-coumaroyl)-(6"-O-E-feruloyl)-β-D-glucopyranoside(21),4,5-di-caffeoylquinic acid butyl ester(22),3,4-di-caffeoylquinic acid butyl ester(23).The IC50 values of compounds 1,7,22-23 against DPPH free radicals were(24.67±1.63)-(53.41±1.61)μmol/L,and the IC50 values of compounds 8,21-23 against ABTS+free radicals were(15.22±0.89)-(41.66±6.29)μmol/L.CONCLUSION Compounds 9,19-23 are isolated from genus Anaphalis for the first time,and 2,10,13,14,16,17,19-23 are first isolated from this plant.Compounds 1,7-8,21-23 have strong antioxidant activity.

Objective To construct a model combining with traditional Chinese medicine(TCM)syndrome for predicting the risk of disease progression in patients with idiopathic membranous nephropathy(IMN)by machine learning methods,thus to quantitatively evaluating the value of TCM syndrome in the prediction of the risk of disease progression in IMN.Methods Monofactor analysis,recursive feature elimination(RFE)and multivariate binary Logistic regression analysis were used to screen the independent related factors affecting the risk of disease progression of IMN,and then a risk prediction model was constructed.A total of 102 patients with IMN were randomly assigned to the training set and the test set in a ratio of 65∶35,and then the comparison was conducted in the performance indicators of accuracy,sensitivity,specificity,F1 value,and area under the receiver operating characteristic(ROC)area under the curve(AUC)of the risk prediction model with or without the inclusion of the TCM syndrome information.Results Before the inclusion of TCM syndrome information,12 clinical characteristic variables for patients with MN were obtained after monofactor analysis combined with RFE screening,and they were age,hemoglobin quantification,urinary occult blood,24-hour urine protein quantification,urine protein-creatinine ratio,estimated glomerular filtration rate(eGFR),creatinine,uric acid,alanine transaminase,anti-phospholipase A2 receptor antibody(PLA2R-Ab),total cholesterol,and low-density lipoprotein cholesterd.A risk cholesterol prediction model containing the above variables was constructed.The multivariate binary Logistic regression analysis showed that the differences of the clinical variables mentioned above between the training-set group and test-set group were statistically significant,and the risk prediction model presented good sensitivity and predictability.Monofactor analysis combined with RFE screening was performed again after the inclusion of TCM syndrome information,and then 14 variables were obtained,which included blood stasis syndrome and dampness obstruction syndrome.The sensitivity and specificity of the model with the inclusion of the TCM syndrome information were significantly improved when compared with those without the inclusion of TCM syndrome information.Conclusion The results of the study initially indicate that TCM syndrome can be used as an important supplementary variable for predicting the risk of disease progression in IMN,and will provide a reference for intelligent diagnosis through the integration of traditional Chinese and western medicine information,and will supply the guidance for the treatment of IMN with TCM.

Objective:To evaluate long-term outcomes of endoscopic papillectomy (EP) for duodenal papillary adenomas and to identify risk factors for incomplete resection.Methods:Clinical data of 180 patients diagnosed as having duodenal papillary adenoma via postoperative pathology after EP in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2010 to December 2022 were retrospectively analyzed. Patients were divided into two groups based on their postoperative margin status: the complete resection group (negative resection margins) and the incomplete resection group (positive/uncertain resection margins). Recurrence rates were compared between the two groups, and logistic regression analysis was performed to identify risk factors for incomplete resection.Results:Among the 180 patients included in the study, 137 underwent complete resection, and 43 had incomplete resections. Recurrence rate was significantly higher in the incomplete resection group than that in the complete resection group (30.2% VS 15.3%, χ2=4.75, P=0.029). logistic regression analysis indicated that high-grade intraepithelial neoplasia was an independent risk factor for incomplete resection ( OR=2.43, 95% CI:1.12-5.26, P=0.024). Conclusion:Patients with incomplete resection after EP have a higher recurrence rate in the long-term follow-up. High-grade intraepithelial neoplasia is an independent risk factor for incomplete resection. Close surveillance and aggressive management are warranted for patients with positive or uncertain resection margins to mitigate the recurrence risk.

As a physical treatment technique, modified electro-convulsive therapy (MECT) is used to treat mental and certain neurological disorders by causing seizures with short, suitable electrical currents applied to the brain while the patient is under general anesthesia and muscle relaxants. MECT is recognized for its therapeutic efficacy and clinical safety, rendering it one of the most prevalent interventions in psychiatric care. To enhance clinical outcomes and minimize adverse effects, this consensus document delineates the indications, therapeutic parameters, therapeutic procedures, potential adverse effects, and associated management strategies for MECT. These guidelines are informed by the latest clinical research and expert consensus, integrating evidence-based medicine methodologies. The objective is to furnish clinicians with precise operational guidelines and to advance the standardization of MECT practices in clinical settings.

Objective:To investigate the correlation between membranous urethral length (MUL) and early urinary continence recovery after robot-assisted radical prostatectomy (RARP).Methods:A retrospective analysis was conducted on 71 prostate cancer patients who underwent RARP by a single surgeon at the PLA General Hospital between January 2020 and December 2023. Patient characteristics included: age of (65.32±6.04) years, BMI (25.21 ± 2.59) kg/m 2, prostate volume 32.41 (24.75, 44.40) ml, PSA 11.67 (8.22, 22.66) ng/ml. Gleason score [6/7/8/9-10: 15 (21.2%)/29 (40.8%)/16 (22.5%)/11 (15.5%)], Clinical stage [cT 1/cT 2/cT 3: 4 (5.6%)/61 (85.9%)/6 (8.5%)]. Measured MUL using multiparametric prostate MRI, median MUL was 13.25 (10.41-14.99) mm. Neurovascular bundle (NVB) preservation in 13 (18.3%) cases. Patients were grouped based on continence recovery at 1 and 3 months post-catheter removal. Age, BMI, prostate volume, PSA, Gleason score, clinical stage, NVB preservation, pathological stage, catheter indwelling time, and MUL were compared between groups. Multivariate analysis identified independent predictors of continence recovery. Results:All 71 surgeries were successful, pathological stage [pT 2/pT 3-4: 47 (66.2%)/24 (33.8%)], and catheter indwelling time 2.7 (2.0, 3.0) weeks. Follow-up data at 2 months were available for 71 patients, at 1 month, 42 patients achieved continence (continence group) and 29 had incontinence (incontinence group).No significant differences were observed between continence and incontinence groups in age [(64.93±6.48)years vs. (65.79±5.89) years], BMI [(26.26±2.52)kg/m 2 vs. (24.52±2.42) kg/m 2], prostate volume [32.00 (24.12, 41.11)ml vs. 33.00 (25.27, 47.97) ml], PSA [12.55 (8.31, 24.00) ng/ml vs. 11.30 (7.92, 20.65) ng/ml], Gleason score [6/7/8/9-10: 6 (14.2%)/18 (42.9%)/12 (28.6%)/6 (14.3%) vs. 9 (31.0%)/11 (37.9%)/4 (13.8%)/5 (17.3%)], clinical stage [cT 1/cT 2/cT 3: 2 (4.8%)/35 (83.3%)/5 (11.9%) vs. 2 (6.9%)/26 (89.7%)/1 (3.4%)], NVB preservation [7 (16.7%) vs. 6 (20.7%)], pathological stage [pT 2/pT 3-4: 27 (64.3%)/15 (35.7%) vs. 20 (69.0%)/9 (31.0%)], or catheter indwelling time [2.6(2.0, 3.0) weeks vs. 2.9 (2.0, 3.4) weeks]. However, MUL was significantly longer in the continence group [13.77 (11.70, 15.32) mm vs. 10.32 (9.65, 13.57) mm, P<0.01]. Follow-up data at 3 months were available for 69 patients, At 3 months, 61 patients achieved continence (continence group) and 8 remained incontinent (incontinence group). No significant differences were observed in age [(64.89±6.25)years vs. (68.13±4.09) years], BMI [(25.34±2.64)kg/m 2 vs. (24.36±2.49) kg/m 2], prostate volume [32.41 (24.44, 44.16)ml vs. 36.13 (27.48, 48.26) ml], PSA [12.50 (8.28, 22.76)ng/ml vs. 13.34 (5.88, 23.39) ng/ml], Gleason score [6/7/8/9-10: 12 (19.7%)/25 (41.0%)/14 (23.0%)/10 (16.3%) vs. 3 (37.5%)/3 (37.5%)/2 (25.0%)/0], clinical stage [cT 1/cT 2/cT 3: 3 (4.9%)/52 (85.2%)/6 (9.8%) vs. 1 (12.5%)/7 (87.5%)/0], NVB preservation [9 (14.8%) vs. 3 (37.5%)], pathological stage [pT 2/pT 3-4: 41 (67.2%)/20 (32.8%) vs. 5 (62.5%)/9 (31.0%)], or catheter indwelling time [2.7(2.0, 3.0)weeks vs. 3.0 (2.3, 3.7) weeks]. MUL remained significantly longer in the continence group [13.57 (10.57, 15.10)mm vs. 10.12 (9.36, 10.42) mm, P=0.002]. Multivariate logistic regression incorporating age, BMI, prostate volume, MUL, NVB preservation, and catheter indwelling time identified MUL as an independent protective factor for continence recovery at both 1 month [ OR=0.62, 95 CI 0.49-0.79, P<0.01] and 3 months [ OR=0.61, 95 CI 0.41-0.92, P=0.017]. Conclusions:MUL is independently associated with early urinary continence recovery after RARP, serving as a protective predictor at both 1 and 3 months after catheter removal.

Objective:To investigate the risk factors for positive surgical margins（PSM）after robot-assisted radical prostatectomy（RARP），and to develop and validate a predictive nomogram.Methods:We retrospectively analyzed the clinicopathological data of 874 prostate cancer patients who underwent RARP performed by a single surgeon at the First Medical Center of Chinese PLA General Hospital between January 2012 and December 2018. Patients were divided into positive surgical margin（n=327）and negative surgical margin（n=547）groups based on postoperative margin status.The PSM group had significantly higher preoperative median tPSA［31.200（19.050，54.400）ng/ml vs. 15.050（9.840，27.590）ng/ml， P<0.01］，higher proportion of patients with PSAD>1 ng/ml 2［49.5%（162/327）vs. 21.2%（116/547）， P<0.01］，biopsy Gleason score ≥8［33.3%（109/327）vs. 21.2%（116/547）， P<0.01］，ISUP grade 4-5［33.3%（109/327）vs. 21.2%（116/547）， P<0.01］，clinical T stage ≥cT 3［11.3%（37/327）vs. 4.2%（23/547）， P<0.01］，and high-risk classification［82.3%（269/327）vs. 55.9%（306/547）， P<0.01］compared to the negative surgical margin group. Conversely，the PSM group had a lower prevalence of hypertension［29.7%（97/327）vs. 40.2%（220/547）， P=0.002］.Patients were randomly split into a training cohort（n=656，75%）and an internal validation cohort（n=218，25%）. An external validation cohort included 71 patients who underwent RARP by different surgeons between January 2014 and December 2016. No significant differences in baseline characteristics were observed between cohorts（ P>0.05）.Univariate and multivariate logistic regression analyses identified independent predictors of PSM，which were incorporated into a nomogram. Predictive performance was assessed using receiver operating characteristic（ROC）curves，decision curve analysis（DCA），and calibration curve. Internal and external validations were performed. Results:The PSM group had longer postoperative hospitalization［6（5，8）vs. 6（5，7）days， P=0.028］，higher rates of pathologic Gleason score ≥8［41.5%（115/277）vs. 24.9%（111/446）， P<0.01］，ISUP grade 4-5［41.5%（115/277）vs. 24.9%（111/446）， P<0.01］，pT 3 stage［52.3%（171/327）vs. 17.4%（95/547）， P<0.01］，pN 1 stage［12.8%（42/327）vs. 3.8%（21/547）， P<0.01］，extracapsular extension［52.3%（171/327）vs. 17.4%（95/547）， P<0.01］，and seminal vesicle invasion［34.6%（113/327）vs. 9.1%（50/547）， P<0.01］.Multivariate analysis identified elevated tPSA（ OR=1.014，95% CI 1.004—1.024，P=0.006）and PSAD ≥0.15 ng/（ml/g）（ OR=11.638，95% CI 1.450—93.396，P=0.021）as independent risk factors for PSM. The area under the ROC curve（AUC）of the nomogram constructed based on the above variables was 0.770（95% CI 0.735—0.805）. The AUC values for the internal and external validation sets were 0.698（95% CI 0.630—0.767）and 0.643（95% CI 0.513—0.774），respectively. The calibration curve demonstrated good agreement between the predicted and observed outcomes，and the DCA indicated that the predictive model has potential clinical utility in decision-making. Conclusion:tPSA and PSAD were identified as independent risk factors for PSM. The nomogram constructed based on these two independent predictive variables effectively predicted PSM after RARP.