Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Objective To explore the effect of shikonin on the recovery of nerve function after acute spinal cord injury(SCI)in rats.Methods 96 male Sprague-Dawley(SD)rats were divided into 4 groups randomly:sham operation group(Group A),sham operation+shikonin group(Group B),SCI+DMSO(Group C),SCI+shikonin group(Group D).The acute SCI model of rats was made by clamp method in groups C and D.After subdural catheterization,no drug was given in group A.rats in groups B and D were injected with 100 mg·kg-1 of shikonin through catheter 30 min after modeling,and rats in group C were given with the same amount of DMSO,once a day until the time point of collection tissue.Basso-Beattie-Bresnahan(BBB)scores were performed on 8 rats in each group at 6,12,and 3 d after moneling,and oblique plate tests were performed on 1,3,7 and 14 d after modeling,and then spinal cord tissues were collected.Eight rats were intraperitoneally injected with propidine iodide(PI)1 h before sacrificed to detection PI positive cells at 24 h in each group.Eight rats were sacrificed in each group at 24 h after modeling,the spinal cord injury was observed by HE staining.The Nissl staining was used to observe survivor number of nerve cells.Western-blot technique was used to detect the expression levels of Bcl-2 protein and apoptosis related protein RIPK1.Results After modeling,BBB scores were normal in group A and B,but in group C and D were significantly higher than those in group A and B.And the scores in group D were higher than those in group C in each time point(P＜0.05).At 12 h after modeling,the PI red stained cells in group D were significantly reduced compared with that in group C,and the disintegration of neurons was alleviated(P＜0.05).HE and Nissl staining showed nerve cells with normal morphology in group A and B at 24h after operation.The degree of SCI and the number of neuronal survival in group D were better than those in group C,the differ-ence was statistically significant at 24h(P＜0.05).The expression of Bcl-2 and RIPK1 proteins was very low in group A and B;The expression of RIPK1 was significantly increased in Group C and decreased in Group D,with a statistically significant dif-ference(P＜0.05);The expression of Bcl-2 protein in group D was significantly higher than that in group C(P＜0.05).Conclu-sion Shikonin can alleviate the pathological changes after acute SCI in rats,improve the behavioral score,and promote the re-covery of spinal nerve function.The specific mechanism may be related to the inhibition of TNFR/RIPK1 signaling pathway mediated necrotic apoptosis.

OBJECTIVE: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G₁-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation ; Matrix Metalloproteinase 9 ; Molecular Docking Simulation ; Cell Cycle ; ErbB Receptors ; Apoptosis ; Colorectal Neoplasms/pathology* ; Cell Line, Tumor

Objective To study chest computed tomography(CT)manifestations in neonates with chronic granulomatous disease(CGD)to provide clues for early diagnosis of this disease.Methods A retrospective analysis was conducted on the clinical data and chest CT scan results of neonates diagnosed with CGD from January 2015 to December 2022 at Anhui Provincial Children's Hospital.Results Nine neonates with CGD were included,with eight presenting respiratory symptoms as the initial sign.Chest CT findings included:consolidation in all 9 cases;nodules in all 9 cases,characterized by multiple,variably sized scattered nodules in both lungs;masses in 4 cases;cavities in 3 cases;abscesses in 6 cases;bronchial stenosis in 2 cases;pleural effusion,interstitial changes,and mediastinal lymphadenopathy each in 1 case.CT enhancement scans showed nodules and masses with uneven or ring-shaped enhancement;no signs of pulmonary emphysema,lung calcification,halo signs,crescent signs,bronchiectasis,or scar lesions were observed.There was no evidence of rib or vertebral bone destruction.Fungal infections were present in 8 of the 9 cases,including 6 with Aspergillus infections;three of these involved mixed infections with Aspergillus,with masses most commonly associated with mixed Aspergillus infections(3/4).Conclusions The primary manifestations of neonatal CGD on chest CT are consolidation,nodules,and/or masses,with Aspergillus as a common pathogen.These features can serve as early diagnostic clues for neonatal CGD.

OBJECTIVE: A core genome multilocus sequence typing (cgMLST) scheme to genotype and identify potential risk clonal groups (CGs) in Proteus mirabilis. METHODS: In this work, we propose a publicly available cgMLST scheme for P. mirabilis using chewBBACA. In total 72 complete P. mirabilis genomes, representing the diversity of this species, were used to set up a cgMLST scheme targeting 1,842 genes, 635 unfinished (contig, chromosome, and scaffold) genomes were used for its validation. RESULTS: We identified a total of 205 CGs from 695 P. mirabilis strains with regional distribution characteristics. Of these, 159 unique CGs were distributed in 16 countries. CG20 and CG3 carried large numbers of shared and unique antibiotic resistance genes. Nine virulence genes ( papC, papD, papE, papF, papG, papH, papI, papJ, and papK) related to the P fimbrial operon that cause severe urinary tract infections were only found in CG20. These CGs require attention due to potential risks. CONCLUSION This research innovatively performs high-resolution molecular typing of P. mirabilis using whole-genome sequencing technology combined with a bioinformatics pipeline (chewBBACA). We found that the CGs of P. mirabilis showed regional distribution differences. We expect that our research will contribute to the establishment of cgMLST for P. mirabilis.
Genome, Bacterial ; Proteus mirabilis/genetics* ; Multilocus Sequence Typing ; Molecular Epidemiology ; Genotype

This study aims to provide evidence for clinical practice by systematically reviewing the efficacy and safety of Gusongbao preparation in the treatment of primary osteoporosis(POP). The relevant papers were retrieved from four Chinese academic journal databases and four English academic journal databases(from inception to May 31, 2022). The randomized controlled trial(RCT) of Gusongbao preparation in the treatment of POP was included after screening according to the inclusion and exclusion criteria. The quality of articles was evaluated using risk assessment tools, and the extracted data were subjected to Meta-analysis in RevMan 5.3. A total of 657 articles were retrieved, in which 15 articles were included in this study, which involved 16 RCTs. A total of 3 292 patients(1 071 in the observation group and 2 221 in the control group) were included in this study. In the treatment of POP, Gusongbao preparation+conventional treatment was superior to conventional treatment alone in terms of increasing lumbar spine(L2-L4) bone mineral density(MD=0.03, 95%CI[0.02, 0.04], P<0.000 01) and femoral neck bone mineral density, reducing low back pain(MD=-1.69, 95%CI[-2.46,-0.92], P<0.000 1) and improving clinical efficacy(RR=1.36, 95%CI[1.21, 1.53], P<0.000 01). Gusongbao preparation was comparable to similar Chinese patent medicines in terms of improving clinical efficacy(RR=0.95, 95%CI[0.86, 1.04], P=0.23). Gusongbao preparation was inferior to similar Chinese patent medicines in reducing traditional Chinese medicine syndrome scores(MD=1.08, 95%CI[0.44, 1.71], P=0.000 9) and improving Chinese medicine syndrome efficacy(RR=0.89, 95%CI[0.83, 0.95], P=0.000 4). The incidence of adverse reactions of Gusongbao preparation alone or combined with conventio-nal treatment was comparable to that of similar Chinese patent medicines(RR=0.98, 95%CI[0.57, 1.69], P=0.94) or conventio-nal treatment(RR=0.73, 95%CI[0.38, 1.42], P=0.35), and the adverse reactions were mainly gastrointestinal discomforts. According to the available data, Gusongbao preparation combined with conventional treatment is more effective than conventional treatment alone in increasing lumbar spine(L2-L4) bone mineral density and femoral neck bone mineral density, reducing low back pain, and improving clinical efficacy. The adverse reactions of Gusongbao preparation were mainly gastrointestinal discomforts, which were mild.
Humans ; Bone Density ; Low Back Pain ; Medicine, Chinese Traditional ; Osteoporosis/drug therapy*