Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Purpose To investigate the clinicopathological features,molecular genetics and prognosis of high grade B cell lymphoma with concurrent MYC rearrangement and 11q aberra-tions(HGBCL-MYC-11q).MethodsThree cases of HGBCL-MYC-11q were reviewed and analyzed using hematoxylin-eosin staining,immunohistochemistry,EBER in situ hybridization and fluorescence in situ hybridization.Clinical data were collected with follow-up.Results All three patients were male,age was 10,61,and 74 years,respectively.All patients had Ann Arbor stage Ⅳ disease.All three cases were biopsies occurring in the nasopharynx,upper pharynx and ileocecus,respectively.Three cases were morphologically similar to diffuse infiltrative growth of tumor cells,moderate or moderately large cells,round to slightly irregular nuclei and easily visible mitotic figures.Focal necrosis was noted in one case.One case exhibited the distinct"starry sky"pattern.All cases expressed CD20,BCL6 and MUM1 and high Ki67 index,two cases expressed CD10 and two cases ex-pressed BCL2.CD3,CD30 and TDT were all negative.EBER in situ hybridization was all negative.FISH analyses using C-MYC break-apart probes were all positive and all cases had 11q aberrations.One case only had the 11q23.3 amplification;and one case only had the 11q24.3 loss.After a follow-up for 1-18 months,one patient died and two patients survived with disease.ConclusionHGBCL-MYC-11q is rare,morphologically similar to BL/HGBCL,with MYC rearrangement and 11q abnormali-ties.We should enhance awareness of the disease and improve more accurate diagnosis and differential diagnosis of the disease.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

To investigate the genomic features and perform cluster analysis of Carbapenem-resistant Klebsiella pneumoniae (CRKP) to provide an experimental basis for guiding the prevention and treatment of CRKP infections.A retrospective case-cohort study was conducted on 19 non-redundant CRKP strains isolated from the Tenth Affiliated Hospital of Southern Medical University between January and June 2023. Whole genome sequencing (WGS) and multilocus sequence typing (MLST) were performed to compare genomic features and analyze the resistance genes and homology of the strains.The results showed that the 19 CRKP strains were isolated from 8 different clinical departments, mainly from respiratory specimens. The whole genome sequencing revealed that the genomic lengths of CRKP ranged from 4.90 to 5.85 Mbp, with contigs N50 values>20 kb for each genome. The median overall GC content was 57.0% (50.4%-57.1%). Comparative genomic analysis identified three regions with high genomic variability. WGS detected 32 resistance genes across 11 categories. All 19 strains carried carbapenem resistance genes ( blaKPC-2 and blaOXA-48), blaTEM-1B extended-spectrum β-lactamase resistance genes, qnrS1 quinolone resistance gene, and fosA fosfomycin resistance gene, with each strain carrying only one carbapenemase gene. The detection rate of blaKPC-2 was 94.7% (18/19). MLST identified three sequence types: ST11, ST437 and ST147, with ST11 being predominant (89.5%, 17/19). Clustering analysis based on acquired resistance genes revealed three clonal transmission patterns among strains 72 and 90, and strains 88, 84, 66 and 79.In conclusion, CRKP strains carry multiple resistance genes, and clustering analysis indicating that nosocomial clonal transmission is closely related to acquired resistance genes. The ST11- blaKPC-2 type strain is the predominant clone. Strengthened surveillance and effective control strategies are necessary to reduce nosocomial transmission of CRKP.

To investigate the genomic features and perform cluster analysis of Carbapenem-resistant Klebsiella pneumoniae (CRKP) to provide an experimental basis for guiding the prevention and treatment of CRKP infections.A retrospective case-cohort study was conducted on 19 non-redundant CRKP strains isolated from the Tenth Affiliated Hospital of Southern Medical University between January and June 2023. Whole genome sequencing (WGS) and multilocus sequence typing (MLST) were performed to compare genomic features and analyze the resistance genes and homology of the strains.The results showed that the 19 CRKP strains were isolated from 8 different clinical departments, mainly from respiratory specimens. The whole genome sequencing revealed that the genomic lengths of CRKP ranged from 4.90 to 5.85 Mbp, with contigs N50 values>20 kb for each genome. The median overall GC content was 57.0% (50.4%-57.1%). Comparative genomic analysis identified three regions with high genomic variability. WGS detected 32 resistance genes across 11 categories. All 19 strains carried carbapenem resistance genes ( blaKPC-2 and blaOXA-48), blaTEM-1B extended-spectrum β-lactamase resistance genes, qnrS1 quinolone resistance gene, and fosA fosfomycin resistance gene, with each strain carrying only one carbapenemase gene. The detection rate of blaKPC-2 was 94.7% (18/19). MLST identified three sequence types: ST11, ST437 and ST147, with ST11 being predominant (89.5%, 17/19). Clustering analysis based on acquired resistance genes revealed three clonal transmission patterns among strains 72 and 90, and strains 88, 84, 66 and 79.In conclusion, CRKP strains carry multiple resistance genes, and clustering analysis indicating that nosocomial clonal transmission is closely related to acquired resistance genes. The ST11- blaKPC-2 type strain is the predominant clone. Strengthened surveillance and effective control strategies are necessary to reduce nosocomial transmission of CRKP.

Purpose To investigate the clinicopathological features,diagnosis,differential diagnosis and molecular charac-teristics desmoid fibromatosis the breast(DFB).Methods The clinicopathological data and prognostic information of 26 pa-tients with desmoid fibromatosis of the breast were collected.Their clinical characteristics,histological morphologies,immu-nophenotypes and molecular characteristics were analyzed.Re-sults All the 26 patients were female,with a median age of 34.5 years and an average age of 36.8 years(range from 13 to 69 years).There were 10 cases in left breast,14 cases in right breast and 2 cases in bilateral breast.Isolated and painless breast masses were found in all patients,and 3 cases were ac-companied by nipple depression.Grossly,most of them showed a poorly circumscribed tan-white to gray mass with a trabeculated appearance.Microscopically,all the tumors were composed of mild spindle cells with varying intervals of collagen fiber bun-dles.The boundary between the tumor and the surrounding breast tissue was not clear,and the tumor cells infiltrated adja-cent tissues,such as breast ducts,lobules,adipose tissue,and skeletal muscle.Uniform spindle or oval cells formed in fascicles and interwoven,without atypical or polymorphism;the nuclear chromatin was sparse or vacuolar,with small nucleoli,but mito-ses were rare or absent.Nuclear accumulation of β-catenin was present in 20 of 26 tumors,SMA was variously positive in 20 of 26,desmin was focally positive in 6 of 26;CKpan,CK5/6,p63,CD34,CD10 and S-100 were all negative.The Ki67 index was 5％-10％.The gene mutations of CTNNB1 exon 3 were found in 18 of 26 by Sanger sequencing,including T41A(83.3％),S45P(11.1％)and S45F(5.6％).Two patients also had familial adenomatous polyposis.Local resection was performed in 23 cases,mastectomy was performed in 2 cases,and one case did not require any additional treatment after core needle biopsy.20 cases were followed up for 1-108 months,and no recurrence occurred.Conclusion Desmoid fibromatosis of the breast is rare,and can mimic breast cancer clinically,ra-diologically and histologically.It should be always considered in differential diagnosis for the spindle cell proliferations of the breast.A diagnosis of DFB can be achieved basing on the typi-cal histopathology,immunohistochemistry,history and gene se-quencing.

[This corrects the article DOI: 10.1016/j.apsb.2021.08.015.].

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Objective To investigate the effect of Kunxian capsule combined with candesartan axetil on blood pressure, renal function, blood lipids and inflammatory factors in patients with chronic glomerulonephritis complicated with hypertension. Methods 101 patients with chronic glomerulonephritis who were admitted to our hospital from November 2017 to December 2019 were selected and randomly divided into observation group (51 cases) and control group (50 cases). The control group was treated with candesartan cilexetil on the basis of conventional treatment, and the observation group was treated with Kunxian capsule on the basis of the control group. The clinical efficacy and adverse reactions of the two groups were compared. Results The total effective rate of the observation group was significantly higher than that of the control group (P<0.05). After treatment, the blood pressure, renal function indexes (24 h Upro, BUN, Scr), blood lipid indexes (TG, TC, LDL-C), and inflammatory factors of the two groups (IL-6, hs-CRP) significantly decreased, and the observation group was significantly lower than the control group (P<0.05). After treatment, the blood lipid index HDL-C of the two groups increased significantly, and the blood lipid index HDL-C of the observation group was significantly higher than that of the control group (P<0.05). Conclusion Kunxian capsule combined with candesartan axetil can enhance the clinical efficacy, improve renal function, regulate blood lipids and reduce inflammation in patients with chronic glomerulonephritis complicated with hypertension.

Osteosarcoma is a kind of bone tumor with highly proliferative and invasive properties, a high incidence of pulmonary metastasis and a poor prognosis. Chemotherapy is the mainstay of treatment for osteosarcoma. Currently, there are no molecular targeted drugs approved for osteosarcoma treatment, particularly effective drugs for osteosarcoma with pulmonary metastases. It has been reported that fibroblast activation protein alpha (FAPα) is upregulated in osteosarcoma and critically associated with osteosarcoma progression and metastasis, demonstrating that FAPα-targeted agents might be a promising therapeutic strategy for osteosarcoma. In the present study, we reported that the FAPα-activated vinblastine prodrug Z-GP-DAVLBH exhibited potent antitumor activities against FAPα-positive osteosarcoma cells in vitro and in vivo. Z-GP-DAVLBH inhibited the growth and induced the apoptosis of osteosarcoma cells. Importantly, it also decreased the migration and invasion capacities and reversed epithelial-mesenchymal transition (EMT) of osteosarcoma cells in vitro and suppressed pulmonary metastasis of osteosarcoma xenografts in vivo. Mechanistically, Z-GP-DAVLBH suppressed the AXL/AKT/GSK-3β/β-catenin pathway, leading to inhibition of the growth and metastatic spread of osteosarcoma cells. These findings demonstrate that Z-GP-DAVLBH is a promising agent for the treatment of FAPα-positive osteosarcoma, particularly osteosarcoma with pulmonary metastases.