Osteoporosis （OP） is a systemic metabolic bone disease characterized by bone microstructure degeneration and bone mass loss， which has a high prevalence and disability rate. Effective prevention and treatment of OP is a major difficulty in the medical community. The nature of OP is that multiple pathological factors lead to the imbalance of human bone homeostasis maintained by osteoblasts and osteoclasts. Ferroptosis is a non-apoptotic cell death pathway， and its fundamental cause is cell damage caused by iron accumulation and lipid peroxidation. Studies have shown that ferroptosis is involved in and affects the occurrence and development of OP， which leads to OP by mediating the imbalance of bone homeostasis. Ferroptosis is an adjustable form of programmed cell death. The intervention of ferroptosis can regulate the damage degree and death process of osteoblasts and osteoclasts， which is beneficial to maintain bone homeostasis， slow down the development process of OP， improve the clinical symptoms of patients， reduce the risk of disability， and improve their quality of life. However， there are few studies on ferroptosis in OP. Traditional Chinese medicine （TCM） is a medical treasure with unique characteristics and great application value in China. It has been widely used in China and has a long history. It has the multi-target and multi-pathway advantages in the treatment of OP， with high safety， few toxic and side effects， and low treatment cost， and has a significant effect in clinical application. The intervention of TCM in ferroptosis to regulate bone homeostasis may be a new direction for the prevention and treatment of OP in the future. This article summarized the regulatory mechanisms related to ferroptosis， discussed the role of ferroptosis in bone homeostasis， and reviewed the current status and progress of active ingredients in TCM compounds and monomers in the regulation of OP through ferroptosis， so as to provide a theoretical basis for the participation of TCM in the prevention and treatment of OP in the future.

AIM:To investigate the effect of a disintegrin and metalloproteinase(ADAM)domain-like decy-sin 1(ADAMDEC1)knockdown on the proliferation,migration and invasion of pancreatic carcinoma cells.METHODS:Expression levels of ADAMDEC1 in pancreatic carcinoma tissues were analyzed using the GEPIA and UALCAN online da-tabases.Western blot analysis was employed to detect the protein expression levels of ADAMDEC1 in pancreatic carcino-ma cell lines(MIA PaCa-2 and PANC-1)and pancreatic ductal cell line(hTERT-HPNE).The effects of ADAMDEC1 knockdown on cell proliferation,migration and invasion were evaluated using CCK-8,colony formation,wound-healing and Transwell assays.Additionally,Western blot analysis was used to detect the effects of ADAMDEC1 knockdown on the expression levels of migration and invasion markers,as well as Wnt/β-catenin signaling pathway-related proteins in pancre-atic carcinoma cells.Furthermore,a recovery experiment was conducted to assess the role of Wnt/β-catenin signaling path-way agonist CHIR-99021 in ADAMDEC1 knockdown-induced inhibition of pancreatic carcinoma cell growth and migra-tion.RESULTS:(1)ADAMDEC1 was highly expressed in pancreatic carcinoma cells.(2)Knockdown of ADAMDEC1 led to a significant reduction in the proliferation,migration and invasion of pancreatic carcinoma cells.(3)Knockdown of ADAMDEC1 resulted in increased E-cadherin protein expression and decreased levels of matrix metalloproteinase 9,N-cadherin and vimentin proteins,alongside a reduction in the expression of Wnt/β-catenin signaling pathway-related pro-teins.(4)Co-treatment of pancreatic carcinoma cells with CHIR-99021 and ADAMDEC1 small interfering RNA reversed the inhibitory effects of ADAMDEC1 knockdown on cell proliferation,migration,and invasion.CONCLUSION:ADAMDEC1 is highly expressed in pancreatic carcinoma.Targeted silencing of ADAMDEC1 has the potential to inhibit the prolifera-tion,migration and invasion of pancreatic carcinoma cells by regulating the Wnt/β-catenin signaling pathway.

The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

This study was aimed at investigating the pathogenic and molecular characteristics of Klebsiella pneumoniae(KP)in fecal samples of diarrhea cases in a district of Beijing.Fecal samples from diarrhea cases in an outpatient department in a district of Beijing from 2018 to 2021 were collected,and used for isolation and culture of KP.The KP strains isolated strains were subjected to drug resistance phenotype testing and whole-genome sequencing.Multilocus sequence typing and whole-genome phyletic evolution analysis were performed on the sequencing results.The cases'epidemiological and clinical characteristics were analyzed.From 2018 to 2021,1 103 fecal samples were collected and detected.The total detection rate of KP was 10.43％(115/1 103),and the infection rate of KP mixed with other diarrhea-causing pathogens was 42.61％(49/115).The positivity rate was slightly high(12.47％,61/489)a-mong females and was highest in young adults 16-45 years of age.Small peaks were observed in January,April to May,and August to September.The gastrointestinal symptoms in cases were mainly nausea and watery stool,and the suspicious food was unknown.Ampicillin,tetracycline,and sulfafurazole were the top three antibiotics to which these 115 KP strains showed resistance,and 29 strains were resistant to multiple antibiotics.The strains were divided into 72 sequence types,among which ST23 was dominant.According to the phylogenetic tree,the strains were divided into four main branches,among which 14 ST23 strains had a very close genetic relationship with the highly virulent NTUH-K2044 reference strain.KP infection persisted in fecal samples from diarrhea cases in the district of Beijing.Women and young adults were particularly susceptible.The drug resistance of KP strains in this region was very serious,and the ST types were diverse.Moreover,the ST23 pathogenic strains were closely related to high virulence strains.

ObjectiveTo explore the clinical diagnosis and treatment of rare primary lumbar intervertebral space infection with Klebsiella pneumoniae and Enterobacter cloacae， and provide clinical experience for the diagnosis and treatment of this rare spinal infection. MethodsAn elderly male patient with low back pain and numbness in the left lower extremity for more than 7 months， which aggravated for more than 1 week， was diagnosed with lumbar disc herniation after laboratory and imaging examinations. After admission， the symptoms became acutely aggravated， and re-examination of lumbar enhanced MRI showed local enhancement at the posterior edge of the L3/4 intervertebral space. The VAS score was 9 points， and the lumbar JOA score was 6 points. A posterior lumbar interbody fusion of L3-L5 was performed， and L3/4 intervertebral disc specimens were collected during the operation for bacterial culture. ResultsBacterial culture results showed Klebsiella pneumoniae and Enterobacter cloacae infection. The patient was treated with sensitive antibiotics for 6 weeks after the operation， and the patient was cured during the follow-up of half a year after the operation. ConclusionFor middle-aged and elderly patients with clinical manifestations of acute severe low back pain or lower extremity pain， the possibility of spinal infection should be considered when routine laboratory and imaging examinations suggest lumbar degenerative diseases.

Humans ; Multiple Myeloma/drug therapy* ; Thalidomide/therapeutic use* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Neoplasm Recurrence, Local/drug therapy*

Objective: To investigate the feasibility of only surgical resection for nasal vestibular squamous cell carcinoma and the efficacy of perforator flap of ipsilateral nasolabial sulcus in repairing postoperative defects. Methods: The clinical data of 8 cases with squamous cell carcinoma of the nasal vestibule who admitted to Department of Facial Plastic and Reconstructive Surgery, Eye & ENT Hospital, Fudan University were analyzed, including 6 males and 2 females, aged from 38 to 75 years. The tumor of the nasal vestibule was eradicated in time after making definite diagnosis of lesions, then the perforators flap of the ipsilateral nasolabial sulcus was used for repairment, without performing further chemotherapy or radiotherapy after surgery. The tumor recurrence, facial appearance, nostril form, donor area scar, nasal ventilation function, and cutaneous sensation were evaluated after surgery. Descriptive analysis was used in this research. Results: There were 2 cases of stage T1 and 6 cases of stage T2 in 8 cases. After 32 to 45 months of following-up, no recurrence accurred and all the flaps survived well. However, there was about 2 mm necrosis of the transplanted flap in the lateral foot of the alar in one case, which was healed well by carrying out wound care after 10 d. And the dark color flap was occurred in another case, showing the flap's backflow trouble, yet it was improved with addressing timely during 5 d postoperation. Pincusion-like deformity of the transplanted flap occurred in 4 cases (50%), which subsided gradually after 6 months. The morphology of the anterior nostril was altered in 4 cases (50%), but there was no ventilation trouble and no need for addressment in any case. The postoperative facial appearance was rated as excellentor good with hidden scar in the donor site, and the sensation of the transplanted flaps was indistinct from the surrounding tissue after 3 months. Conclusions: Surgical resection of nasal vestibular squamous cell carcinoma with tumor stage T1-2 is a feasible treatment. And it is the one of the best reconstructive methods of the perforator flap of the ipsilateral nasolabial sulcus to repair the deformities after the surgery.
Male ; Female ; Humans ; Perforator Flap/transplantation* ; Cicatrix/surgery* ; Neoplasm Recurrence, Local/surgery* ; Plastic Surgery Procedures ; Carcinoma, Squamous Cell/surgery* ; Skin Transplantation/methods* ; Treatment Outcome

OBJECTIVE: Xiaotan Sanjie recipe (XTSJ), a Chinese herbal compound medicine, exerts a significant inhibitory effect on gastric cancer (GC) metastasis. This work investigated the mechanism underlying the XTSJ-mediated inhibition of GC metastasis. METHODS: The effect of XTSJ on GC metastasis and the associated mechanism were investigated in vitro, using GC cell lines, and in vivo, using a GC mouse model, by focusing on the expression of Glc-N-Ac-transferase V (GnT-V; encoded by MGAT5). RESULTS: The migration and invasion ability of GC cells decreased significantly after XTSJ administration, which confirmed the efficacy of XTSJ in treating GC in vitro. XTSJ increased the accumulation of E-cadherin at junctions between GC cells, which was reversed by MGAT5 overexpression. XTSJ administration and MGAT5 knockdown alleviated the structural abnormality of the cell-cell junctions, while MGAT5 overexpression had the opposite effect. MGAT5 knockdown and XTSJ treatment also significantly increased the accumulation of proteins associated with the E-cadherin-mediated adherens junction complex. Furthermore, the expression of MGAT5 was significantly lower in the lungs of BGC-823-MGAT5 + XTSJ mice than in those of BGC-823-MGAT5 + solvent mice, indicating that the ability of gastric tumors to metastasize to the lung was decreased in vivo following XTSJ treatment. CONCLUSION XTSJ prevented GC metastasis by inhibiting the GnT-V-mediated E-cadherin glycosylation and promoting the E-cadherin accumulation at cell-cell junctions. Please cite this article as: Huang N, He HW, He YY, Gu W, Xu MJ, Liu L. Xiaotan Sanjie recipe, a compound Chinese herbal medicine, inhibits gastric cancer metastasis by regulating GnT-V-mediated E-cadherin glycosylation. J Integr Med. 2023; 21(6): 561-574.
Male ; Mice ; Animals ; Stomach Neoplasms/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Glycosylation ; Cell Line, Tumor ; Cadherins/metabolism*

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

To investigate the regulation of N6- methyladenosine ( m6A ) modification on L-type calcium channels in atrial myocytes under high hydrostatic pressure, mediated by methyltransferase-like protein 3 ( METTL3 ). Methods C57BL/6J mice were randomly assigned to the control group and the hypertension group ( treated with continuous administration of angiotensin for four weeks ). Masson staining was used to observe the fibrosis of mouse atrial tissue, while dot blot assay and Western blot were used to detect the levels of m6A, METTL3, and Cavi1 2 in the atrial tissue. A high hydrostatic pressure model was constructed using the HL-1 cell line cultured in vitro, and METTL3 was intervened to observe changes in m6A expression levels, METTL3 and Cavi1 2 levels in cells,and action potential duration ( APD ) and L-type calcium current ( I