Objective To evaluate the clinical application effect of fracture liaison service(FLS)mode after percutaneous vertebroplasty(PVP)/percutaneous kyphoplasty(PKP)for thoracolumbar fragility fracture.Methods A prospective study was conducted,and 762 patients with thoracolumbar fragility fracture who underwent PVP/PKP in the department of orthopedics in our hospital from January 2018 to May 2021 were included and divided into the control group(374 cases)and the observation group(388 cases)according to the random number table method.Patients in the control group received routine osteoporosis intervention,while the patients in the observation group implemented FLS through Blue Bull Medical Care or Chronic Health APP on the basis of the control group to systematically manage the osteoporosis treatment after discharge.The follow-up lasted for 12 months,and the 8-item Morisky medication adherence scale(MMAS-8)score,pain visual analogue scale(VAS)score,Oswestry disability index(ODI)score and Hamilton depression rating scale(HAMD)score at discharge,and 6 months and 12 months after discharge of the two groups were compared.The incidences of re-fracture and constipation 6 months and 12 months after discharge of the two groups were compared.The Cobb angle and bone mineral density T-value of injured vertebrae 6 months and 12 months after discharge of the two groups were compared.Results There was no statistically significant difference in the MMAS-8 score,VAS score,ODI score or HAMD score at discharge of patients between the two groups(P>0.05).The VAS score,ODI score and HAMD score 6 months and 12 months after discharge in the observation group were lower than those in the control group(P<0.05),the MMAS-8 score in the observation group was higher than that in the control group(P<0.05),and the incidences of re-fracture and constipation in the observation group were lower than those in the control group(P<0.05).There was no statistically significant difference in the Cobb angle of injured vertebrae 12 months after discharge of patients between the two groups(P>0.05).The bone mineral density T-value 12 months after discharge in the observation group was higher than that in the control group(P<0.05).Conclusion The FLS mode can significantly improve the medication compliance of patients,relieve pain,depression and constipation,improve bone mineral density,and significantly reduce the incidence of vertebral re-fracture in patients after vertebral augmentation surgery;however,it has no significant effect on the Cobb angle of injured vertebrae.

Objective:To investigate the expression level,clinical significance and function of circular RNAs(circRNAs)circ_0073585 in the bone marrow of patients with acute myeloid leukemia(AML).Methods:The expression levels of circ_0073585 in bone marrow samples of 106 newly diagnosed AML patients and 38 controls were detected by real-time quantitative PCR(RQ-PCR).The differences were compared between the two groups and their clinical significance was analyzed.The diagnostic value of circ_0073585 expression for AML was evaluated by receiver operating characteristic curve(ROC).THP-1 cells with lentivirus overexpressing circ_0073585 vector and empty vector were divided into two groups:circ_0073585-THP-1 and NC-THP-1 group.CCK-8 assay and flow cytometry were used to study the effects of circ_0073585 on THP-1 cell proliferation,survival,apoptosis and drug sensitivity.Results:Compared with the controls,the expression level of circ_0073585 in the bone marrow of AML patients was significantly reduced(P＜0.001).There was a statistically significant difference between the high and low expression groups of circ_0073585 in the white blood cell count,platelet count(P＜0.01)and chromosome risk(P＜0.05).Compared with NC-THP-1 cells,the proliferation and viability of circ_0073585-THP-l cells were weakened(P＜0.01),the apoptosis rate was increased(P＜0.01),and the sensitivity to homoharringtonine(P＜0.05)and daunorubicin hydrochloride(P＜0.001)was increased.Conclusion:The expression level of circ_0073585 is decreased in AML patients.Overexpression of circ_0073585 can inhibit the proliferation and viability of leukemic cells,promote apoptosis,and increase sensitivity of leukemia cells to chemotherapy drugs.

AIM:To investigate the anti-fibrotic effect of Panax notoginseng saponins(PNS)in arecoline(ANE)-induced oral submucous fibrosis,and to analyze the effect of PNS on nuclear factor E2-related factor 2(Nrf2)/glu-tamate-cysteine ligase catalytic subunit(GCLC)signaling pathway.METHODS:CCK-8 assay was used to evaluate the effects of different concentrations of PNS and arecoline on the survival rate of human immortalized keratinocyte cell line Ha-CaT.The results of CCK-8 were used to select 75 mg/L arecoline,and 25,50 and 100 mg/L PNS as subsequent experi-mental concentrations.The cells were set as blank control group,model group,and low,medium and high doses(25,50 and 100 mg/L)of PNS groups.The protein and mRNA expressions of collagen type I(COL-I),E-cadherin,Nrf2,GCLC and glutathione reductase(GR)in each group were detected by Western blot and RT-qPCR.Immunofluorescence method was used to detect the entry of Nrf2 into the nucleus.Biochemical kits were used to detect the content of glutathione(GSH),nicotinamide adenine dinucleotide phosphate(NADPH)and malondialdehyde(MDA),and superoxide dis-mutase(SOD)activity in each group of cells.DCFH-DA fluorescent probe was used to detect the content of intracellular reactive oxygen species(ROS).RESULTS:Compared with the blank control group,the protein and mRNA expression of COL-I in the model group was up-regulated,and the protein and mRNA levels of E-cadherin,Nrf2,GCLC,nuclear Nrf2 and GR were down-regulated.The content of NADPH,MDA and ROS in the cells increased,and the content of GSH and the activity of SOD was significantly reduced.Compared with the model group,the protein and mRNA expression of COL-I was down-regulated,and the protein and mRNA expression of E-cadherin,Nrf2,GCLC,nuclear Nrf2 and GR were up-regulated in PNS 50 and 100 mg/L groups.Compared with the model group,the content of NADPH,MDA and ROS in cells decreased,and the content of GSH and the activity of SOD was significantly enhanced(P<0.05 or P<0.01).CON-CLUSION:Panax notoginseng saponins have anti-fibrosis effects in HaCaT cells,and their mechanism may be related to the activation of Nrf2/GCLC signaling pathway,thereby resisting oxidative stress and improving oral submucosal fibrosis.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

ObjectiveTo describe the epidemic characteristics of COVID-19 after policy adjustment from “Category B notifiable disease with category A management” to “Category B notifiable disease with category B management”， and to explore the protective effect of previous infection with SARS-CoV-2 on common symptoms of reinfection. MethodsHealthcare workers infected with SARS-CoV-2 in a grade A tertiary hospital in Shanghai were included in the study from December 4， 2022 to January 11， 2023. Data on demographic characteristics， clinical symptoms， medical history， and COVID-19 vaccination history were collected. We determined the epidemiological curve and characteristics， and then compared the difference in the severity of clinical symptoms between primary and reinfection subjects. ResultsA total of 2 704 cases were included in the study， of which 45 had reinfection， 605 （22.4%）were males， 608 （22.5%）were doctors， 1 275 （47.2%） were nurses， and 2 351 （86.9%） received ≥3 doses of COVID-19 vaccination. The average age of these healthcare workers was （34.9±9.1） years old. The number of cases with mild/moderate illness， asymptomatic infection， fever， headache， dry cough， expectoration， and chest tightness were 2 704 （100.0%）， 92 （3.4%）， 2 385 （88.2%）， 2 066 （76.4%）， 1 642 （60.7%）， 1 807 （66.8%）， and 439 （16.2%）， respectively. Reinfection was a protective factor for fever （OR=0.161， P<0.001）， headache （OR=0.320， P<0.001）， and peak body temperature （β=-0.446， P<0.001）. ConclusionFollowing the COVID-19 policy adjustment as a category B notifiable disease， healthcare workers at a grade A tertiary hospital in Shanghai predominantly experiences mild to moderate COVID-19 symptoms. Reinfection results in milder clinical manifestations， with a lower proportion of being asymptomatic.

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.

The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.

Objective To investigate the effects of fast-track anesthesia on hemodynamics, awakening quality, and neurological function in patients undergoing cardiac surgery. Methods A total of 130 patients undergoing cardiac surgery were selected and were randomly divided into control group (n=65) and study group (n=65). The clinical data of the patients were collected, and the hemodynamic parameters, awakening quality, neurological function, and incidence of postoperative complications were compared between the two groups. Results The study group had lower dosages of fentanyl citrate injection and rocuronium bromide compared with the control group (P < 0.05). After anesthesia induction and tracheal intubation, the heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), cardiac index (CI), and bispectral index (BIS) were changed compared with before anesthesia induction in both groups, but the degree of change in the study group was less than that in the control group (P < 0.05). The study group had shorter postoperative recovery time to breathe, awakening time, extubation time, ICU stay time, and postoperative hospital stay compared with the control group, the incidence of restlessness after extubation was lower in the study group than in the control group (P < 0.05). The study group had lower levels of neuron-specific enolase (NSE) and β-amyloid protein (Aβ) at 180 min after arterial cannulation compared with the control group (P < 0.05). The total incidence of postoperative complications was 3.08% in the study group, which was lower than 16.92% in the control group (P < 0.05). Conclusion Fast-track anesthesia can effectively stabilize hemodynamics in patients undergoing cardiac surgery, improve awakening quality and neurological function, and reduce the incidence of postoperative complications.

Objective: To evaluate the inhibitory effect of tumor vaccines in colon carcinoma model mice. Methods: Mouse bone marrow⁃derived dendritic cells（BMDCs）were stimulated by using CpG β⁃glucan nanoparticles（CNP）in vitro. The BMDCs were divided into PBS group，NP group（without CpG nanoparticles），Lysate group（MC38 cell lysate）and CpG group（CpG1826），which were determined for the expression of marker molecules on the surface by flow cytometry and for the contents of interleukin⁃6（IL⁃6）and IL⁃12p40 in the culture supernatant by ELISA. The tumor lysate nano⁃vaccine was pre⁃ pared by mixing 50 mg／mL tumor lysate（MC38 cell lysate）with 200 mg／mL CNP in a volume ratio of 1∶1，with which mice were subcutaneously immunized as Vaccine group. Vaccine group，PBS group，CNP group and Lysate group were im⁃ munized once a week，for three times in total. Mice were subcutaneously inoculated with MC38 cells，2 × 105 cells for each， in the right lower limb 1 h after the last immunization，and measured for tumor volume once every three days to plot the tumor growth curve. The ratios of CD3+ CD4+ T and CD3+ CD8+ T cells in the blood were analyzed by flow cytometry and the levels of tumor necrosis factor⁃α（TNF⁃α）and interferon γ（IFNγ）in the blood and spleen of mice were determined by ELISA. Results: CNP effectively increased the expression of CD11c+ CD80+，CD11c+ CD86+，CD11c+ MHC⁃Ⅱ+ and the secretion of IL⁃6 and IL⁃12p40 in BMDCs in vitro，which were significantly higher than those in other 4 groups（t = 4. 3 ~ 46. 2，each P < 0. 05）. Compared with that of the other three groups，the tumor volume of mice in Vaccine group decreased significantly（t =2.6~3.4，eachP <0. 05）；TherewasnosignificantdifferenceinCD3+ CD8+ TandCD3+ CD8+ Tcellratios（t = 0.5~ 1. 9，each P > 0. 05）；The content of IFNγ in blood increased significantly（t = 3. 8 ~ 4. 6，P < 0. 05），while thatof TNF⁃α showed no significant difference（t = 0. 4 ~ 2. 0，each P > 0. 05）；However，the contents of IFN γ and TNF⁃α in spleen increased significantly（t = 6. 3 ~ 13. 0，each P < 0. 001）. Conclusion The prepared nano⁃vaccine of tumor lysate improvedtheimmune level in mice and effectively inhibited the growth of colon carcinoma.

OBJECTIVE: To explore whether casticin (CAS) suppresses stemness in cancer stem-like cells (CSLCs) obtained from human cervical cancer (CCSLCs) and the underlying mechanism. METHODS: Spheres from HeLa and CaSki cells were used as CCSLCs. DNA methyltransferase 1 (DNMT1) activity and mRNA levels, self-renewal capability (Nanog and Sox2), and cancer stem cell markers (CD133 and CD44), were detected by a colorimetric DNMT activity/inhibition assay kit, quantitative real-time reverse transcription-polymerase chain reaction, sphere and colony formation assays, and immunoblot, respectively. Knockdown and overexpression of DNMT1 by transfection with shRNA and cDNA, respectively, were performed to explore the mechanism for action of CAS (0, 10, 30, and 100 nmol/L). RESULTS: DNMT1 activity was increased in CCSLCs compared with HeLa and CaSki cells (P<0.05). In addition, HeLa-derived CCSLCs transfected with DNMT1 shRNA showed reduced sphere and colony formation abilities, and lower CD133, CD44, Nanog and Sox2 protein expressions (P<0.05). Conversely, overexpression of DNMT1 in HeLa cells exhibited the oppositive effects. Furthermore, CAS significantly reduced DNMT1 activity and transcription levels as well as stemness in HeLa-derived CCSLCs (P<0.05). Interestingly, DNMT1 knockdown enhanced the inhibitory effect of CAS on stemness. As expected, DNMT1 overexpression reversed the inhibitory effect of CAS on stemness in HeLa cells. CONCLUSION CAS effectively inhibits stemness in CCSLCs through suppression of DNMT1 activation, suggesting that CAS acts as a promising preventive and therapeutic candidate in cervical cancer.
Female ; Humans ; Cell Line, Tumor ; HeLa Cells ; Neoplastic Stem Cells/metabolism* ; RNA, Small Interfering/metabolism* ; Uterine Cervical Neoplasms/metabolism*