Hospital acquired pneumonia (HAP) and ventilatorassociated pneumonia (VAP) are common hospital-acquired infections with higher mortality, longer hospital stay and more hospitalization expenses. With the latest research results and evidence-based guideline methodology, Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS) have collaborated to create updated guidelines for the diagnosis and treatment of HAP and VAP in 2016. It is worth critically reading and thinking that most recommendations are supported by low-quality or very-low quality evidence and some strong recommendations is different from the actual clinical work in China. We will focus on these topics that are associated closely with clinical practice and inconsistent with the current implementation in China to provide better understanding of the guideline.

OBJECTIVE: To explore the effect and mechanism of kidney-warming and astringent therapy in treating nephrotic syndrome patients with deficiency of spleen and kidney yang and overflow of water, and to observe the change of plasma endothelin and interleukin-2 receptor after treatment. METHODS: Forty-four patients were randomly divided into conventional steroid treated group (control group, 20 cases) and conventional steroid plus kidney-warming and astringent therapy treated group (treatment group, 24 cases). The levels of plasma endothelin (ET) and soluble interleukin-2 receptor (sIL-2) were observed. RESULTS: Before treatment, plasma ET and sIL-2 in the patients were significantly higher than those in healthy people (P<0.01). After treatment, the ET and sIL-2 levels were obviously improved in both treated groups (P<0.05) and the improvement in the treatment group was more obvious. The difference between the two treated groups after treatment was significant (P<0.05). CONCLUSION: Conventional treatment plus kidney-warming and astringent therapy can effectively improve the levels of plasma ET and sIL-2 in treating nephrotic syndrome patients with deficiency of spleen and kidney yang and overflow of water, and hence alleviate the damage of renal tissue.

Objective To observe the effect of raloxifene, a selective estrogen receptor modulator, on osteoporosis in the osteoprotegerin (OPG) gene knock-out female and male mice. Methods Two groups of OPG gene deficient (OPG-/-) female and male mice, 20 mice in each group, were assigned to raloxifene-treated (3 mg The effect of raloxifene was evaluated by comparing the values of bone mineral density (BMD) , bone strength,histomorphometric measurement and osteoclast number between the raloxifene treated group and placebo group.Results As compared with placebo group osteoporotic manifestations were improved in OPG-/- female mice treated with raloxifene orally. BMD was increased both in lumbar vertebrae (P<0.05) and femurs (P<0.01).Bone strength was measured in femurs by three-point bending test and vertebrae by stress test. Results showed that ultimate load, ultimate stress and Young's modulus were increased both at lumbar and femur bone, suggesting decreased risk of fracture. Tartrate-resistant acid phosphatase, a marker enzyme of osteoclasts, was detected, and the number of osteoclasts declined significantly after the treatment of raloxifene. At the same time, results of histomorphometric measurements indicated that bone trabecular volume was increased and bone formation rate decreased from(8.05±4.02)mm3·mm-2·year-1 to (5.48±1.89)mm3·mm-2· year-1(P＜0.05).These findings were found in the group of OPG-/- female mice treated with reloxifene but not in male mice. Conclusions Raloxifene is effective in treating osteoporosis in female OPG-/- mice, indicating that its action is at least in part independent of OPG gene. But it is ineffective in male OPG-/- mice.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.