[摘 要] 目的：探讨甲硫氨酸限制对肺腺癌（LUAD）细胞增殖、凋亡及磷酸戊糖途径的影响。方法：将H1299、A549细胞分为Met+组和Met−组，分别用含100 μmol/L或不含甲硫氨酸的培养基连续培养4 d，采用细胞计数法评估甲硫氨酸处理对H1299和A549细胞增殖的影响，PI染色法检测细胞周期分布，Annexin Ⅴ-PE/7AAD标记细胞凋亡，利用DCFH-DA探针检测细胞内ROS水平，WST-8法和DTNB法分别测定细胞内NADPH与GSH含量；通过癌症基因组图谱（TCGA）数据库分析葡萄糖-6-磷酸脱氢酶（G6PD）和6-磷酸葡萄糖酸脱氢酶（6PGD）表达与甲硫氨酸代谢通路的关系；采用WB法检测甲硫氨酸处理及回补甲硫氨酸下游代谢产物S-腺苷甲硫氨酸（SAM）对LUAD细胞中磷酸戊糖途径关键酶G6PD和6PGD表达的影响。结果：甲硫氨酸限制显著抑制H1299和A549细胞增殖（均P < 0.01），将细胞周期阻滞于G2/M期（均P < 0.05），显著升高细胞内总ROS水平（均P < 0.001）并促进细胞凋亡（均P < 0.001）；同时，甲硫氨酸限制显著降低了细胞内NADPH和GSH水平（均P < 0.01），抑制DNA合成（均P < 0.01）。分析TCAG数据发现，G6PD和6PGD表达水平与甲硫氨酸代谢通路呈正相关（均P < 0.001），甲硫氨酸限制下调G6PD和6PGD蛋白表达（均P < 0.01），而回补SAM可部分逆转甲硫氨酸限制对G6PD和6PGD的表达的抑制（均P < 0.01），提示甲硫氨酸通过SAM合成调控磷酸戊糖途径。结论：甲硫氨酸限制通过抑制磷酸戊糖途径抑制LUAD细胞增殖，为甲硫氨酸限制疗法治疗LUAD提供实验依据。

As a practical carrier for promoting the tiered diagnosis and treatment model, the medical consor-tium is of great significance for balancing medical resources and boosting medical service efficiency. The construction of medical consortiums not only improves the accessibility of high-quality medical resources for patients, but also enhances the diagnostic and treatment level of member units. Meanwhile, it provides space for the leading hospital to adjust the structure of diseases and improve the level of discipline construction. As the core of medical insurance payment reform, DRG, through indicators such as the case mix index(CMI) and the number of diagnosis related group (DRG), provides objective and quantified data support for case management and disease structure optimization, thus effectively guiding the rational allocation of medical resources and the adjustmentof diseases and surgical types within the medical consortium. Comprehensive use of DRG evaluation indicators can construct a multidimensional medical consortium construction evaluation system, provides a clear direction for medical consortium cooperation, thereby promoting the overall healthy and sustainable development of medical consortiums and achieving a win-win situation for all parties involved. This paper, based on the "1+5+1" medical consortium cooperation model centered around Peking Union Medical College Hospital, utilizes DRG indicators to analyze the benefits for patients, member hospitals, and the leading hospital during the medical consortium construction process, with the hope of providing reference for the construction of a medical consortium evaluation system.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare debilitating autoimmune disease of the central nervous system. Three monoclonal antibodies were recently approved as maintenance therapies for aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive NMOSD (eculizumab, inebilizumab, and satralizumab). Neurol Neuroimmunol Neuroinflamm published international Delphi consensus on the management of AQP4-IgG+ NMOSD in May 31, 2023. Twenty-five statements reached consensus after two voting rounds by 24 Delphi panel experts. Inebilizumab and satralizumab have been listed in China, and off-label immunosuppressants and biologics are also used in clinical practice. However, there are no standard treatment recommendations in use of these biologics and maintenance therapy of NMOSD. Therefore, the interpretation of this consensus, focusing on the initial use of monoclonal drugs, the conversion between monoclonal drugs and immunosuppressants, as well as the application and safety of special populations, is conducive to improving the normative and effective use of of monoclonal drugs in NMOSD y ophthalmologists and neurologists

Orthodontically induced tooth root resorption (OIRR) is a serious complication during orthodontic treatment. Stimulating cementum repair is the fundamental approach for the treatment of OIRR. Parathyroid hormone (PTH) might be a potential therapeutic agent for OIRR, but its effects still lack direct evidence, and the underlying mechanisms remain unclear. This study aims to explore the potential involvement of long noncoding RNAs (lncRNAs) in mediating the anabolic effects of intermittent PTH and contributing to cementum repair, as identifying lncRNA-disease associations can provide valuable insights for disease diagnosis and treatment. Here, we showed that intermittent PTH regulates cell proliferation and mineralization in immortalized murine cementoblast OCCM-30 via the regulation of the Wnt pathway. In vivo, daily administration of PTH is sufficient to accelerate root regeneration by locally inhibiting Wnt/β-catenin signaling. Through RNA microarray analysis, lncRNA LITTIP (LGR6 intergenic transcript under intermittent PTH) is identified as a key regulator of cementogenesis under intermittent PTH. Chromatin isolation by RNA purification (ChIRP) and RNA immunoprecipitation (RIP) assays revealed that LITTIP binds to mRNA of leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) and heterogeneous nuclear ribonucleoprotein K (HnRNPK) protein. Further co-transfection experiments confirmed that LITTIP plays a structural role in the formation of the LITTIP/Lgr6/HnRNPK complex. Moreover, LITTIP is able to promote the expression of LGR6 via the RNA-binding protein HnRNPK. Collectively, our results indicate that the intermittent PTH administration accelerates root regeneration via inhibiting Wnt pathway. The lncRNA LITTIP is identified to negatively regulate cementogenesis, which activates Wnt/β-catenin signaling via high expression of LGR6 promoted by HnRNPK.
Mice ; Animals ; Cementogenesis ; Wnt Signaling Pathway ; beta Catenin/metabolism* ; Heterogeneous-Nuclear Ribonucleoprotein K/metabolism* ; RNA, Long Noncoding/genetics* ; Parathyroid Hormone ; Receptors, G-Protein-Coupled/metabolism*

Objective: To explore the relationship between parent child relationship and rebelliousness of junior middle school students in boarding schools and to provide a scientific basis for preventing the occurrence of youth rebellion. Methods: A cluster sampling method was used to investigate parent child separation, family intimacy, and rebellion among 1 790 junior high school students in one boarding middle school in Lujiang County, Hefei City, Anhui Province in January 2020, and the influence of parent child relationship on students rebelliousness was analyzed by Chi square test and binary Logistic regression. Results: The detection rate of rebelliousness among participants was 21.45%(384/ 1 790 ). Junior middle school students who were in senior grade (second and third grades), reported higher household economic status and no communication with parents during the past month were more likely to have rebelliousness( OR=1.83, 1.89, 1.80, 1.77 , P <0.05); Junior middle school students with higher parental warmth and intimacy were less likely to have rebelliousness( OR=0.52, 0.71, P <0.05); Gender, length of boarding, maternal education, frequency of meeting parents during boarding, and childhood experience of separation with parents showed no statistical significance on rebelliousness( P >0.05). Conclusion The detection rate of rebellious psychology among junior high school students in boarding schools is high, and good parent child relationship is the protective factor of rebellious psychology. Parents should pay attention to contact with their boarding children and strengthen communication to reduce rebelliousness among them.

Objective:To explore the clinical effects of the "Disease-Characteristics" project in improving the nursing quality of patients with diabetic retinopathy (DR) .Methods:Based on the content framework of "Disease-Characteristics", authoritative data of UpToTate and various guidelines were transformed into evidence for clinical application through the steps of evidence-based nursing, and a standardized "Disease-Characteristics" project for DR patients was constructed. Convenience sampling was adopted to select nurses who worked in the Shanghai Eye Hospital and the Ophthalmology Department of Shanghai First People's Hospital from January 1, 2018 to June 30, 2019 as research nurses. Convenience sampling was used to select 223 DR patients admitted to the two hospitals from October 30, 2018 to January 31, 2019 (before implementation) as the control group, and 261 patients with DR admitted from February 1, 2019 to April 30, 2019 (after implementation) as the observation group. We observed and compared indicators such as the correct rate of nurses' assessment of each key link of DR patients before and after implementation, the awareness rate of patients' DR-related knowledge, and the incidence of postoperative complications of patients.Results:After the implementation, the scores of the nurses in the assessment of each key link of DR patients increased from (90.36±1.16) to (96.72±1.13) , and the difference was statistically significant ( t=52.990, P<0.05) . The disease-related knowledge score of DR patients increased from (74.330±12.154) to (78.386±10.094) , and the difference was statistically significant ( t=4.010, P<0.05) . Postoperative complications such as persistent high intraocular pressure, vitreous rebleeding, inflammatory edema and diplopia were improved, and the differences were statistically significant ( χ2=7.131, 5.618, 5.788, 6.128; P<0.05) . Conclusions:The "Disease-Characteristics" project plan based on the best evidence has a certain significance for improving the nursing quality of DR and the prognosis of patients.

Periodontitis patients are at risk of alveolar bone loss during orthodontic treatment. The aim of this study was to investigate whether intermittent parathyroid hormone (1-34) treatment (iPTH) could reduce alveolar bone loss during orthodontic tooth movement (OTM) in individuals with periodontitis and the underlying mechanism. A rat model of OTM in the context of periodontitis was established and alveolar bone loss was observed. The control, iPTH and iPTH + stattic groups received injections of vehicle, PTH and vehicle, or PTH and the signal transducer and activator of transcription 3 (STAT3) inhibitor stattic, respectively. iPTH prevented alveolar bone loss by enhancing osteogenesis and suppressing bone resorption in the alveolar bone during OTM in rats with periodontitis. This effect of iPTH was along with STAT3 activation and reduced by a local injection of stattic. iPTH promoted osteoblastic differentiation and might further regulate the Wnt/β-catenin pathway in a STAT3-dependent manner. The findings of this study suggest that iPTH might reduce alveolar bone loss during OTM in rats with periodontitis through STAT3/β-catenin crosstalk.
Animals ; Homeostasis ; Humans ; Osteogenesis ; Parathyroid Hormone ; Periodontitis/drug therapy* ; Rats ; STAT3 Transcription Factor/metabolism* ; Tooth Movement Techniques ; beta Catenin

Objective To investigate the relationship between vWF levels and ADAMTS13 levels of DVT (venous thrombosis) in patients with cervical cancer,and then to evaluate the predictive value of vWF levels and ADAMTS13 levels of cervical cancer patients with DVT. Methods A total of sixty-six patients diagnosed as cervical cancer and treated from June 2015 to June 2016 in Weinan Maternal and Child Health Hospital were enrolled,and their baseline data,pathological type,tumor classification,TNM staging,vWF, ADAMTS13 levels and Autar score were recorded. All patients were followed up for 1 year and the patients with adverse outcomes were defined as poor prognosis group during the follow-up period while the patients whose disease progression free were defined as good prognosis group. Univariate analysis showed that the incidence of venous thrombosis in patients with cervical cancer was affected; Cox proportional hazard model further assessed the impact of all statistically significant factors on the occurrence of venous thrombosis in patients; t test showed the distribution of influential factors between the two groups; ROC curve was used to analyze the sensitivity and specificity of vWF and ADAMTS13 levels in predicting the occurrence of venous thrombosis in cervical cancer patients. Results At the end of the follow-up,among the 66 patients,Six were not followed and 40 had good prognosis without venous thrombosis,which was a good prognosis group; Twenty had poor prognosis,i. e. venous thrombosis,which was a poor prognosis group,including 5 deaths. The poor prognosis rate was 30. 30%. Univariate Cox proportional hazard model results showed that vWF (P＝0. 023, (95%CI: 1. 743－1. 215)) and ADAMTS13 (P＝0. 037,(95%CI: 1. 158－1. 566)) had a significant effect on the patients with venous thrombosis. The levels of vWF (( 0. 535 ± 0. 075) μg/L) and ADAMTS13 ((69. 453±10. 284)%) in good prognosis group were significantly lower than those in poor prognosis group ((0. 592 ± 0. 082 ) μg/L, ( 79. 245 ± 11. 477 )%), and the differences between the two groups were statistically significant (t＝2. 690,3. 345,P＜0. 05). Under ROC curve,the AUC of vWF level was 0. 841,the sensitivity and specificity were 55% and 97. 5% respectively,and that of ADAMTS13 level was 0. 906,the sensitivity and specificity were 85% and 80%,respectively. Conclusion The levels of vWF and ADAMTS13 have a good predictive effect on the occurrence of venous thrombosis in patients with cervical cancer. It is expected to be used as a routine evaluation index to predict the occurrence of venous thrombosis in patients with cervical cancer after treatment.

Objective To apply the Plan -Do -Check -Act ( PDCA ) cycle in glucose management in inpatients with diabetes , in order to decrease the incidence of hypoglycemia and related complications .Methods 517 inpatients with diabetes were divided into 4 groups according to the quarter ,the monthly incidence rates of hypo-glycemia were collected.The association of monthly incidence of hypoglycemia with age (≥65 years),longer diabetic history (≥5 years),lower C-peptide (<0.370nmol/L),receiving combined regimen (basal insulin plus 3 doses of pre-prandial short-acting insulin ) were analyzed .PDCA cycle was applied for hypoglycemia detection and etiolo-gy control in order to achieve quality improvement via effective glucose control measures .Theχ2 test was used to ana-lyze the incidence of the hypoglycemia in each group .The hypoglycemic incidence based on different characteristics , were also compared with the overall hypoglycemic incidences of all patients .Results The incidence of hypoglycemia was significantly reduced with the application of PDCA cycle in inpatients with diabetes ,from 44.09％ in the first quarter to 13.04％ in the fourth quarter (χ2 =32.815,P<0.001).The annual hypoglycemic incidence rate was 26.89％.The patients with low C-peptide or receiving combined regimen had significantly higher incidence rate of hypoglycemia (53.57％and 31.88％) as compared to general inpatients with diabetes (χ2 =35.721,7.105,all P<0.05).Conclusion The application of PDCA cycle can effectively decrease the incidence of hypoglycemia ,and it can be a great asset for management of inpatients with diabetes .

Objective To study the application of walking combined with Buerger exercise in the treatment of grade 0 diabetic foot.Methods Eighty patients with grade 0 diabetic foot were randomly divided into observation group and control group.The control group was trained by walking exercise .The observation group was trained by walking combined with Buerger exercise through 12 months of training.The changes of self-sensory symptoms,ABI and DAWV were observed.Results The self-sensory symptoms of the two groups were significantly decreased (observation group: markedly effective 15 cases,effective 19 cases;control group: markedly effective 5 cases,effective 23 cases).The effective rate of the observation group was higher than that of the control group (85% vs.70%,χ2 =7.831,P <0.05).The ABI ratio of the two groups were higher than those before treatment ,and the ABI ratio of the observation group was higher than that of the control group [(0.889 ±0.113) vs.(0.842 ±0.124),t =1.772 P <0.05].The ratio of DAWV in the observation group was higher than that in the control group [(6.772 ±0.435)cm/s vs.(6.543 ±0.552)cm/s,t =2.061,P <0.05].Conclusion Walking combined with Buerger exercise can improve the blood flow velocity and blood flow of the collateral circulation of the lower limbs of patients with grade 0 diabetic foot,and improve the self-sensory symptoms of peripheral neuropathy .