PLOD2 promotes colorectal cancer progression by stabilizing USP15 to activate the AKT/mTOR signaling pathway

Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) has been reported as an oncogenic gene, affecting various malignant tumors, including endometrial carcinoma, osteosarcoma, and gastric cancer. These effects are mostly due to the enhanced deposition of collagen precursors. However, more studies need to be conducted on how its lysyl hydroxylase function affects cancers like colorectal carcinoma (CRC). Our present results showed that PLOD2 expression was elevated in CRC, and its higher expression was associated with poorer survival. Overexpression of PLOD2 also facilitated CRC proliferation, invasion, and metastasis in vitro and in vivo. In addition, PLOD2 interacted with USP15 by stabilizing it in the cytoplasm and then activated the phosphorylation of AKT/mTOR, thereby promoting CRC progression. Meanwhile, minoxidil was demonstrated to downregulate the expression of PLOD2 and suppress USP15, and the phosphorylation of AKT/mTOR. Our study reveals that PLOD2 plays an oncogenic role in colorectal carcinoma, upregulating USP15 and subsequently activating the AKT/mTOR pathway.     

The Optimal Period of Staged Bilateral Total Knee Arthroplasty Procedures under Enhanced Recovery: A Retrospective Study

Objective

The implications of the interval of staged bilateral total knee arthroplasty (TKA) procedures for postoperative complications and costs are not clear. We aimed to determine the optimal time interval between the two stages of bilateral TKA procedures under the enhanced recovery after surgery (ERAS) protocol.

Methods

This retrospective study of collected data included bilateral TKA cases under the ERAS protocol performed between 2018 and 2021 at the West China Hospital of Sichuan University. The staged time was subdivided into three groups according to the interval between the first TKA and second contralateral TKA: group 1: 2- to 6-month, group 2: 6- to 12-month, and group 3: >12 months. The primary outcome was the incidence of postoperative complications. The secondary outcomes were the length of hospital stay (LOS), hemoglobin (Hb) decrease, hematocrit (Hct) decrease, and albumin (Alb) decrease.

Results

We analyzed 281 patients who underwent staged bilateral TKAs between 2018 and 2021 at the West China Hospital of Sichuan University. Regarding postoperative complications, there were no statistically significant differences among the three groups (P = 0.21). For the mean LOS, the 6- to 12-month group had a significantly shorter LOS compared with the 2- to 6-month group (P < 0.01). There was also a significant decrease in Hct of the 2- to 6-month group compared with the 6- to 12-month group and the >12 months group (P = 0.02; P < 0.05, respectively).

Conclusion

Staging the second arthroplasty for more than a half year seems to offer a reduction in the rate of postoperative complications and LOS under ERAS protocol. ERAS shortens the interval of staged bilateral TKA by at least 6 months for patients who might receive their second surgery without the need to wait for an extended period.     

UPLC-MS/MS法同时测定补中益气丸(水丸)中6种化合物含量

目的 建立UPLC-MS/MS法同时测定补中益气丸(水丸)中黄芪甲苷、毛蕊异黄酮苷、橙皮苷、阿魏酸、甘草酸和甘草苷的含量。方法 采用Agilent Zorbax Eclipse XDB-C18色谱柱(100 mm × 2.1 mm, 1.8 μm)，流动相为5 mmol/L乙酸铵溶液-甲醇(含0.1%甲酸)，梯度洗脱；质谱离子化方式为电喷雾源(ESI)，采用多级反应离子监测模式(MRM)定量分析。结果 各化合物在相应浓度范围内线性关系均良好，r2值为0.994~0.999，加标回收率范围为86.7%~103.5%，相应的RSD为3.8%~7.6%。结论 本方法定性和定量准确可靠，重复性好、基质干扰小、灵敏度高，满足补中益气丸(水丸)中6种化合物含量的测定要求。     

Influence of leptin and compression in GAS-6 mediated homeostasis of periodontal ligament cell

Growth arrest-specific protein 6 (GAS-6) regulates immunomodulatory and inflammatory mechanisms in periodontium and may participate in obesity predisposition. This study aimed to determine whether GAS-6 is associated with the homeostasis of periodontal ligament (SV-PDL) cells in the presence of adipokines or compressive forces. The SV-PDL cell line was used. Western blots were employed for TAM receptors detection. Cells were stimulated using different concentrations of GAS-6. The migration, viability, and proliferation were measured by a standard scratch test, MTS assay, and immunofluorescent staining. The mRNA expression was analyzed by RT-PCR. Release of TGF-β1, GAS-6, and Axl were verified by ELISA. Western blot shows that TAM receptors are expressed in SV-PDL cells. GAS-6 has a promoting effect on cell migration and proliferation. RT-PCR analysis showed that GAS-6 induces Collagen-1, Collagen-3, Periostin, and TGF-β1 mRNA expression whereas it reduces Caspase-3, Caspase-8, Caspase-9, and IL-6 mRNA expression. Further, secreted GAS-6 in SV-PDL is reduced in response to both compressive forces and leptin and upregulated by IL-6. Additionally, ADAM-10 inhibition reduces GAS-6 and Axl release on SV-PDL cells. TAM receptors especially Axl are identified as the receptors of GAS-6. GAS-6/TAM interactions contribute to periodontal ligament cells homeostasis. Leptin inhibits the GAS-6 release independently of ADAM-10 metalloprotease.     

中药干预椎间盘退变治疗腰椎间盘突出症作用机制研究进展

腰椎间盘突出症（LDH）是一种常见的骨科疾病。椎间盘退变是其主要的病理基础，椎间盘生物学活性是影响椎间盘退变程度的重要指标，椎间盘细胞受病理因素影响，会加快衰老，出现细胞代谢障碍，导致细胞内环境稳态破坏，使其生物学活性降低，进一步导致了椎间盘退变的发生。目前现代医学对于LDH的治疗主要集中在手术治疗和非甾体抗炎药等，但是手术创伤较大、非甾体抗炎药较大的不良反应等影响了这类手段的临床疗效。现代基础研究证实，中药（单味药/复方）在治疗疾病过程中具有多成分、多通路、多靶点的特点，能够有效提高椎间盘细胞生物学活性，降低应激反应，抑制细胞凋亡，促进细胞自噬。主要能通过抗炎镇痛、改善微循环、调节免疫功能、促进软骨再生和调节神经系统功能等作用机制来改善LDH的临床症状，在LDH的治疗方面具有独特优势。     

安徽省2013-2021监测年度流感流行特征及感染风险的相关因素分析

目的 分析安徽省流感流行特征与量化不同因素对流感发生的影响,为更好地开展流感防控工作提供科学依据。方法 资料来源于中国流感监测信息系统2013年4月1日至2021年3月31日安徽省网络报告数据,对2013-2021监测年度安徽省的流感样病例(ILI)和RT-PCR结果进行描述性分析和影响因素分析。结果 安徽省2013年4月1日至2021年3月31日哨点医院ILI就诊百分比(ILI%)为3.80%(1 209 142/31 779 987),总体呈上升趋势,其中2017-2018监测年度较高,为4.30%(191 148/4 448 211)。0~4岁婴幼儿的ILI构成比较高(54.14%,654 676/1 209 142);安徽省阜阳市ILI%较高(6.25%,236 863/3 788 863)。实验室监测结果显示,8家流感监测年度哨点医院ILI中流感阳性率为16.38%(34 868/212 912),总体呈逐年上升趋势,其中2017-2018监测年度较高,为26.19%(6 936/26 488)。5~14岁学龄儿童阳性率较高(28.81%,13 869/48 144),16个城市中芜湖市阳性率较高(22.01%,2 693/122 237)。流感活动呈现冬春季单峰与冬春季、夏季双峰的交替,且各亚型交替流行,夏季流感优势亚型为A(H3N2)亚型。多因素logistic回归模型结果显示,2017-2018监测年度、5~14岁儿童、冬季、皖南地区的阳性率更高。结论 2013-2021监测年度安徽省流感流行具有明显的季节性,且在2013-2021监测年度ILI%和流感阳性率呈现上升趋势。因此,提示应在冬春流感季到来之前保障疫苗供应,同时加强疫苗接种健康教育,以避免流感高发期的感染风险。