Objective To discuss the value of clinical radiomic nomogram(CRN)and deep convolutional neural network(DCNN)in distinguishing atypical pulmonary hamartoma(APH)from atypical lung adenocarcinoma(ALA).Methods A total of 307 patients were retrospectively recruited from two institutions.Patients in institu-tion 1 were randomly divided into the training(n=184:APH=97,ALA=87)and internal validation sets(n=79:APH=41,ALA=38)in a ratio of 7∶3,and patients in institution 2 were assigned as the external validation set(n=44:APH=23,ALA=21).A CRN model and a DCNN model were established,respectively,and the performances of two models were compared by delong test and receiver operating characteristic(ROC)curves.A human-machine competition was conducted to evaluate the value of AI in the Lung-RADS classification.Results The areas under the curve(AUCs)of DCNN model were higher than those of CRN model in the training,internal and external validation sets(0.983 vs 0.968,0.973 vs 0.953,and 0.942 vs 0.932,respectively),however,the differences were not statistically significant(p=0.23,0.31 and 0.34,respectively).With a radiologist-AI com-petition experiment,AI tended to downgrade more Lung-RADS categories in APH and affirm more Lung-RADS cat-egories in ALA than radiologists.Conclusion Both DCNN and CRN have higher value in distinguishing APH from ALA,with the former performing better.AI is superior to radiologists in evaluating the Lung-RADS classification of pulmonary nodules.

Objective:To investigate the clinical application effect of double-layer soft tissue(DLST)suture closure technique in patients with mandible medication-related osteonecrosis of the jaw(MRONJ)of early and medium stages resulted in application of anti-bone-resorptive drugs.Methods:Early to me-dium stage mandible MRONJ patients who underwent surgical treatment in the fourth ward of Peking Uni-versity School and Hospital of Stomatology from October 2021 to September 2022 were included.Clinical information of the patients were collected,including primary disease,concomitant disease,medication regimen(drug type,duration of medication),MRONJ stage,clinical symptoms,imaging manifestations,etc.During surgery,after using marginal mandibulae resection to remove the necrotic bone,the wound was closed using DLST closure technique.Regular post-operative follow-up was performed to evaluate the therapeutic effect and complications of the DLST technique,the pain score and functional status of the patiens were evaluated.Results:This study totally included 13 patients,12 women and 1 man,aged(66.69±13.14)years.Seven patients had osteoporosis,2 had lung cancer,3 had breast cancer and 1 had prostate cancer among their primary diseases;7 had no concomitant diseases,2 had diabetes melli-tus,2 had cardiovascular disease and 1 had dry syndrome.Intravenous zoledronic acid were used in 9 patients,the average duration was(37.7±20.0)months,and other drugs,such as letrozole tablets were taken in 7 patients at the same time;Denosumab injection was used in 3 patients for an average of(10.3±11.9)months;Alendronate sodium tablets were taken in 5 patients for an average of(55.20± 27.20)months,and prednisone acetate tablets or acarbose tablets were taken to varying degrees in 2 pa-tients.The average post-operative follow-up was 11.9 months(9 to 17 months),and all the 13 patients were cured without complications,such as pus overflow and so forth.The pre-operative score of Karnof-sky performance status(KPS)in the patients was 68.46±14.05,and the post-operative score was 82.31±15.36,and the difference was statistically significant(P＜0.05).The pre-operative score of visual analogue scale(VAS)in the patients was 5.77±0.73 and the post-operative score was 0.38±0.51,and the difference had statistical significance(P＜0.001).Conclusion:The double-layer soft tissue suture closure technique can achieve good clinical results in patients with MRONJ of the man-dible using anti-bone-resorptive drugs alone,and can provide clinical treatment ideas for MRONJ patients with more complicated drug use.

Herpes zoster of trigeminal nerve was a common skin disease caused by varicella-zoster virus infection.Simple involvement of the third branch of trigeminal nerve was rare,and so were oral complica-tions such as pulpitis,periodontitis,spontaneous tooth loss,bone necrosis,etc.This article presented a case of herpes zoster on the third branch of the left trigeminal nerve complicated with left mandibular osteonecrosis.We reported the case of a 64-year-old man with sudden pain in the left half of the tongue 1 month ago,and then herpes on the left facial skin appeared following with acute pain.The local hospital diagnosed it as herpes zoster and treated it with external medication.A few days later,he developed gum pain in the left mandibular posterior tooth area.He was admitted to Peking University School and Hospital of Stomatology one week ago with loose and dislodged left posterior tooth accompanied by left mandibular bone surface exposure.Clinical examination showed bilateral symmetry and no obvious restriction of mouth opening.Visible herpes zoster pigmentation and scarring on the left side of the face appeared.The left mandibular posterior tooth was missing,the exposed bone surface was about 1.5 cm x0.8 cm,and the surrounding gingiva was red and swollen,painful under pressure,with no discharge of pus.The re-maining teeth in the mouth were all m degree loosened.Imageological examination showed irregular low-density destruction of the left mandible bone,unclear boundary,and severe resorption of alveolar bone.The patient was diagnosed as left mandibular osteonecrosis.Under general anesthesia,left mandibular le-sion exploration and curettage+left mandibular partial resection+adjacent flap transfer repair were performed.The patient was re-exmained 6 months after surgery,there was no redness,swelling or other abnormality in the gums and the herpes pigmentation on the left face was significantly reduced.Unfortu-nately,the patient had complications of postherpetic neuralgia.This case indicate that clinicians should improve their awareness of jaw necrosis,a serious oral complication of trigeminal zoster,and provide ear-ly treatment.After the inflammation was initially controlled,surgical treatment could be considered to remove the necrotic bone,curettage the inflammatory granulation tissue,and extraction of the focal teeth to avoid further deterioration of the disease.

Objective To explore the value of combined prediction model based on clinical and CT radiomics features in discriminating atypical pulmonary hamartoma(APH)from atypical lung adenocarcinoma(ALA).Methods A total of 290 patients with APH and ALA confirmed by pathology were retrospectively selected.250 patients from the First Affiliated Hospital of Anhui Medical University were randomly assigned into a training set(APH=91,ALA=84)and an internal validation set(APH=39,ALA=36)at a ratio of 7∶3,and other 40 patients from the First Affiliated Hospital of USTC were assigned as an external validation set(APH=21,ALA=19).The independent model and multivariate logistic regression combined model were constructed using the selected clinical-CT features and radiomics features,respectively,and a nomogram was drawn.Receiver operating characteristic(ROC)curve and DeLong test were used to evaluate and compare the performances of the models.Results The area under the curve(AUC)of the combined model established by 3 clinical-CT features and 4 radiomics features in the training set was 0.980,which was higher than that of clinical-CT model(AUC=0.885,P＜0.001)and radiomics model(AUC=0.975,P=0.042).The AUC of the combined model in the internal and external validation sets(0.963 vs 0.917)were also higher than those of clinical-CT model(0.858 vs 0.774)and radiomics model(0.953 vs 0.897),respectively.Conclusion The combined prediction model based on clinical and CT radiomics features can improve the differential diagnosis ability of APH and ALA.

Triptolide is a key active component of the widely used traditional Chinese herb medicine Tripterygium wilfordii Hook.F.Although triptolide exerts multiple biological activities and shows promising efficacy in treating inflammatory-related diseases,its well-known safety issues,especially reproductive toxicity has aroused concerns.However,a comprehensive dissection of triptolide-associated testicular toxicity at single cell resolution is still lacking.Here,we observed testicular toxicity after 14 days of triptolide exposure,and then constructed a single-cell transcriptome map of 59,127 cells in mouse testes upon triptolide-treatment.We identified triptolide-associated shared and cell-type specific differentially expressed genes,enriched pathways,and ligand-receptor pairs in different cell types of mouse testes.In addition to the loss of germ cells,our results revealed increased macrophages and the inflammatory response in triptolide-treated mouse testes,suggesting a critical role of inflammation in triptolide-induced testicular injury.We also found increased reactive oxygen species(ROS)signaling and down-regulated pathways associated with spermatid development in somatic cells,especially Leydig and Sertoli cells,in triptolide-treated mice,indicating that dysregulation of these signaling pathways may contribute to triptolide-induced testicular toxicity.Overall,our high-resolution single-cell landscape offers comprehensive information regarding triptolide-associated gene expression profiles in major cell types of mouse testes at single cell resolution,providing an invaluable resource for understanding the underlying mechanism of triptolide-associated testicular injury and additional discoveries of therapeutic targets of triptolide-induced male reproductive toxicity.

Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing. This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and the therapeutic potential of Bifidobacterium breve (B. breve). A mouse hard palate mucosal defect model was used to investigate the influence of sunitinib and/or zoledronate on wound healing. The volume and density of the bone under the mucosal defect were assessed by micro-computed tomography (micro-CT). Inflammatory factors were detected by protein microarray analysis and enzyme-linked immunosorbent assay (ELISA). The senescence and biological functions were tested in oral mucosal stem cells (OMSCs) treated with sunitinib. Ligated loop experiments were used to investigate the effect of oral B. breve. Neutralizing antibody for interleukin-10 (IL-10) was used to prove the critical role of IL-10 in the pro-healing process derived from B. breve. Results showed that sunitinib caused oral mucosal wound healing impairment in mice. In vitro, sunitinib induced cellular senescence in OMSCs and affected biological functions such as proliferation, migration, and differentiation. Oral administration of B. breve reduced oral mucosal inflammation and promoted wound healing via intestinal dendritic cells (DCs)-derived IL-10. IL-10 reversed cellular senescence caused by sunitinib in OMSCs, and IL-10 neutralizing antibody blocked the ameliorative effect of B. breve on oral mucosal wound healing under sunitinib treatment conditions. In conclusion, sunitinib induces cellular senescence in OMSCs and causes oral mucosal wound healing impairment and oral administration of B. breve could improve wound healing impairment via intestinal DCs-derived IL-10.
Animals ; Mice ; Interleukin-10 ; Bifidobacterium breve ; Up-Regulation ; Angiogenesis Inhibitors ; Sunitinib ; X-Ray Microtomography ; Administration, Oral ; Wound Healing ; Antibodies, Neutralizing

Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.

Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18β-GA)is a natural com-pound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in Asia.In the present study,we demonstrated that 18β-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18β-GA inhibited the expression of α-smooth muscle actin and collagen type Ⅰ alpha-1.Using a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon reso-nance,we found that 18β-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18β-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated HSCs.PRDX1 knockdown also led to ROS-mediated apoptosis in activated HSCs.Collectively,our findings revealed the target proteins and molecular mechanisms of 18β-GA in ameliorating hepatic fibrosis,highlighting the future development of 18β-GA as a novel therapeutic drug for hepatic fibrosis.

When nanoparticles were introduced into the biological media, the protein corona would be formed, which endowed the nanoparticles with new bio-identities. Thus, controlling protein corona formation is critical to

Membrane-disruptive peptides/peptidomimetics (MDPs) are antimicrobials or anticarcinogens that present a general killing mechanism through the physical disruption of cell membranes, in contrast to conventional chemotherapeutic drugs, which act on precise targets such as DNA or specific enzymes. Owing to their rapid action, broad-spectrum activity, and mechanisms of action that potentially hinder the development of resistance, MDPs have been increasingly considered as future therapeutics in the drug-resistant era. Recently, growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other agents. In this review, we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs, and summarize the current development and mechanisms of MDPs alone or in combination with other agents. Notably, this review highlights recent advances in the design of various MDP-based drug delivery systems that can improve the therapeutic effect of MDPs, minimize side effects, and promote the co-delivery of multiple chemotherapeutics, for more efficient antimicrobial and anticancer therapy.