Rare diseases still lack effective treatments, and the development of drugs for rare diseases (known as orphan drugs) is an urgent medical problem. As natural active ingredients in living organisms, some biomacromolecule drugs have good biocompatibility, low immunogenicity, and high targeting. They have become one of the most promising fields in drug research and development in the 21st century. However, there are still many obstacles in terms of in vivo delivery. In view of the unique advantages of nanocarriers prepared from polymers, lipids, organic biomimetic and inorganic materials in drug delivery, researchers are committed to building an efficient delivery system with versatility and synergy to solve the bottleneck issues in treating rare diseases with biomacromolecule drugs. Therefore, this article reviews the research progress of nanocarrier delivering proteins, peptides and nucleic acids in the field of rare disease treatment in the past ten years, which provides ideas for researches on biomacromolecule drug nanosystems in the field of treatment of rare diseases.

ObjectiveTo explore the rehabilitation outcome of personalized pulmonary rehabilitation therapy in pneumoconiosis patients in the rehabilitation station. Methods A total of 42 pneumoconiosis patients were selected as the study subjects from seven pneumoconiosis rehabilitation stations in Xinjiang Uygur Autonomous Region using the judgment sampling method. Patients were treated with personalized rehabilitation therapy for three months, and the outcome was analyzed. Results The six-minute walking test distance, maximum inspiratory pressure, maximum expiratory pressure, forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and FEV₁/FVC ratio of the pneumoconiosis patients were higher after rehabilitation therapy than those before therapy (all P<0.05). The score of Chronic Obstructive Pulmonary Disease Assessment Test of patients after therapy was lower than that in pre-treatment (P<0.05). There was no significant difference in respiratory difficulty, Borg scale, balance ability, depression symptoms, anxiety symptoms, nutritional status scores, body mass index, blood oxygen saturation, and heart rate before and after rehabilitation therapy (all P>0.05). Conclusion The individualized pulmonary rehabilitation therapy of pneumoconiosis patients at pneumoconiosis rehabilitation station can improve the respiratory muscle strength and lung function of patients, and improve their quality of life.

Obiective Alzheimer’s disease (AD) is a degenerative disease of the central nervous system (CNS) caused by a variety of risk factors. There are various pathological changes, but apoptosis of the neurological meridian cells is one of the most important pathological bases. Hyperlipidemia is a high-risk factor for the development of AD, which can lead to increased levels of oxidized low-density lipoprotein (ox-LDL) in brain tissues. PCSK9 is a protease closely related to lipid metabolism, but studies have shown that it may be related to the development of AD. LRP1 is abundantly expressed in neuronal cells, and it is an important transporter for the clearance of Aβ. There is now a large amount of literature confirming that PCSK9 can induce the degradation of LRP1. PI3K/AKT is an important signaling pathway in vivo, which plays an important role in apoptosis, and there is now a large amount of literature confirming that LRP1 activates the PI3K/AKT pathway, which has an anti-apoptotic effect. So can PCSK9 affect the PI3K/AKT pathway through LRP1 and thus regulate neuronal apoptosis? This deserves further investigation.The aim of this study was to explore the role of PCSK9 in mediating ox-LDL pro-apoptotic neuronal cell death and its mechanism, and then further elaborate the mechanism of hyperlipidemia leading to neurodegenerative diseases such as AD. MethodsFirstly, PC12 cells were treated with different concentrations of ox-LDL (0, 25, 50, 75 and 100 mg/L) for 24 h. Oil red O staining was used to detect lipid accumulation in PC12 cells, Hoechst33258 staining and flow cytometry to detect apoptosis in PC12 cells, ELISA to detect the content of Aβ secreted by PC12, Western blot to detect expression of SREBP2, PCSK9 and LRP1. Then PC12 cells were treated with 75 mg/L ox-LDL for different times (0, 6, 12, 24, 48 h), and Western blot were performed to detect the expression of SREBP2, PCSK9 and LRP1. Finally, after transfecting 100 nmol/L PCSK9 siRNA into PC12 cells for 48 h, PC12 cells were treated with 75 mg/L ox-LDL for 24 h, Hoechst33258 staining and flow cytometry to detect apoptosis rate of PC12 cells, and Western blot to detect PCSK9, LRP1, PI3K, AKT, P-PI3K , P-AKT, NF-κB, Bcl-2, Bax, Caspase-9 and Caspase-3 expression, and ELISA detected Aβ content secreted by PC12 cells. Resultsox-LDL increased lipid accumulation and promoted apoptosis and Aβ secretion in PC12 cells, as well as increasing the expression of SREBP2 and PCSK9 and decreasing the expression of LRP1 in PC12 cells. pCsk9 siRNA could be inhibited through the PI3K/AKT pathway and the NF-κB-Bcl-2/Bax-Caspase-9/3 pathway to inhibit ox-LDL-induced apoptosis in PC12 cells while increasing Aβ secretion in PC12 cells. Conclusionox-LDL plays a bidirectional regulatory role in ox-LDL-induced apoptosis of PC12 cells by inducing an increase in PCSK9 expression and a decrease in LRP1 expression in PC12 cells, which in turn affects different signaling pathways downstream.

kidney deficiency and blood stasis are believed to be the key pathogenesis of recurrent implantation failure （RIF）， and therefore， it is proposed to take kidney-supplementing and blood-invigorating as the basic treatment method， and use it by stages to assist the controlled superovulation program of in vitro fertilization-embryo transfer （IVF-ET）. The focus should be put on nourishing kidney yin， soothing the liver and invigorating blood during down-regulation period， using kidney yin-nourishing medicinals and modified Qinghao Biejia Decoction （青蒿鳖甲汤）. During the ovulation induction period， the focus should be put on nourishing kidney yang， replenishing blood， and promoting blood circulation， with self-made Bushen Culuan Formula （补肾促卵方） in modifications. After transplantation， it is suggested to put focus on tonifying the kidneys and replenishing essence， and self-made Wuzi Yanzong Guchong Decoction （五子衍宗固冲汤） in modifications can be used. At the same time， fetal protection treatment should be carried out for pregnant women， and modified Shou Tai Pill （寿胎丸） can be used to tonify the kidneys and calm the fetus.

The emerging and re-emerging arthropod-borne infectious diseases pose a serious threat to global public health security. Field and laboratory studies of arthropods of medical importance are essential and critical for the prevention and control of arthropod-borne infectious diseases. Various institutions or universities in China have been conducting research in the field or laboratory study of arthropods of medical importance, but up to 2023, it is still lacking detailed biosafety guidelines or recommendations that can guide the related work for arthropods of medical importance. In order to proactively address potential biosafety issues in the field or laboratory activities related to arthropods of medical importance, improve the standardization of arthropod biosafety classification, operations, and protection, and ensure the safety of practitioners, an expert consensus on the biosafety recommendation of arthropods of medical importance in field and laboratory has been developed, aiming to guide the future work of arthropods and ensure the national biosafety and biosecurity of China.

Purpose To investigate the clinical value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)-enhanced MRI for the preoperative evaluation of colorectal cancer liver metastases(CRCLM).Materials and Methods Fifty-six CRCLM patients with 156 CRCLM lesions confirmed by surgical pathology in the First Affiliated Hospital of Henan University of Chinese Medicine from September 2019 to March 2023 were collected,and all underwent dynamic Gd-EOB-DTPA-enhanced MRI.The characteristic manifestations of T2WI,diffusion-weighted imaging(DWI),arterial phase and hepatobiliary phase(HBP)were observed,and the detection rate of each sequence was calculated,and then the signal intensity ratio of lesions to liver parenchyma on HBP and the apparent diffusion coefficient(ADC)were calculated.The ADC values of lesions with reversed target and target signs and lesions with homogeneous and heterogeneous hypointensity on HBP and the detection rate of each sequence were compared.Results Among 156 CRCLM lesions,20.51%(32/156)and 38.46%(60/156)exhibited a target appearance on T2WI,51.28%(80/156)displayed a target sign on DWI,73.72%(115/156)showed rim enhancement on the arterial phase,and 34.62%(54/156)presented a target sign on HBP.The mean ADC value of lesions with reversed target and target signs on HBP did not significantly differ from that of lesions with homogeneous and heterogeneous hypointensity on HBP[(0.98±0.43)×10-3 mm2/s vs.(1.01±0.47)×10-3 mm2/s;t=-0.340,P=0.327].Based on the size of CRCLM lesions,three groups were categorized,including<1.0 cm(41 lesions),1.0-2.0 cm(55 lesions),and>2.0 cm(60 lesions).The overall detection rate of HBP(96.79%)was the highest compared with T2WI,DWI and Gd-EOB-DTPA four-phase dynamic contrast-enhanced multiphase imaging(P<0.05).Regarding<1.0 cm lesions,the detection rate of HBP(87.80%)was superior to that of T2WI,DWI and Gd-EOB-DTPA four-phase dynamic contrast-enhanced multiphase imaging(P<0.05).Conclusion Gd-EOB-DTPA-enhanced MRI has important clinical value for the preoperative evaluation of CRCLM,especially the features of target sign or reversed target sign on HBP and the excellent efficacy of detecting microscopic lesions.

Objective To retrieve,extract,evaluate,and integrate the relevant evidence of postoperative pulmonary rehabilitation management in patients with lung cancer complicated with chronic obstructive pulmonary disease,so as to provide an evidence-based basis for improving the quality of postoperative pulmonary rehabilitation.Methods Relevant literature on postoperative pulmonary rehabilitation of lung cancer complicated with chronic obstructive pulmonary disease were searched by computer from clinical decisions,guideline websites,professional association websites,and comprehensive databases.The types of the literature included clinical decisions,guidelines,expert consensuses,evidence summaries,systematic reviews,meta-analyses,and randomized controlled trials.The retrieval time limit was from the establishment of the database to September 2023.Results A total of 19 articles were included,including 4 clinical decisions,3 guidelines,6 expert consensuses,1 evidence summary,3 systematic reviews,and 2 randomized controlled trials.Through reading,extraction and classification,23 pieces of best evidence were finally formed,including multidisciplinary cooperation,evaluation,pulmonary rehabilitation strategies and health education.Conclusion This study summarizes the best evidence for postoperative lung rehabilitation management in patients with lung cancer and chronic obstructive pulmonary disease.Clinical medical staff can implement practical evidence for postoperative lung rehabilitation based on actual situations,and promote the transformation of evidence-based knowledge into practice.

Purpose To construct and validate a machine learning-based diagnostic model for distinguishing between Mycobacterium avium-intracellular complex pulmonary disease(MAC-PD)and pulmonary tuberculosis(PTB)via chest CT images.Materials and Methods Retrospective data from patients diagnosed with MAC-PD and PTB between May 2021 and August 2022 at Beijing Chest Hospital,Capital Medical University,which were collected as the training set.The prospective external validation set was obtained from patients at the First Affiliated Hospital of Henan University of Chinese Medicine between September 2022 and May 2023.Clinical and radiological data were analyzed,and multivariable logistic regression,random forest and support vector machine(SVM)models were established and externally validated using the validation set.The diagnostic performance of models were evaluated using receiver operating characteristic curve and precision-recall curve,and the differences of the areas under the curve of various models were compared via the Delong test.Results There were significant differences in age and hemoptysis rate between the two groups(t=30.414,P<0.001;χ2=6.186,P=0.013).There were statistically significant differences in cavity types and morphology between the two groups(χ2=6.546,P=0.011;χ2=24.113,P<0.001),but there was no significant difference in the distribution and characteristics of cavitary lesions(P>0.05).There were significant differences in the types and distribution of bronchiectasis between the two groups(χ2=4.634,P=0.031;χ2=23.145,P<0.001).Compared with logistic regression and random forest models,the SVM model had better differential diagnostic performance,and the area under the receiver operating characteristic curve,sensitivity,specificity,accuracy,positive predictive value and negative predictive value were 0.960(95%CI 0.935-0.985),85.7%,93.6%,90.5%,93.3%,88.0%and 0.885(95%CI 0.803-0.967),respectively,76.7%,80.0%,78.3%,79.3%,77.4%.The precision-recall curve showed that the SVM model had high precision and low recall,that was,the model performs well.Conclusion The machine learning-based models exhibits excellent diagnostic performance and can assist in differentiating MAC-PD and PTB.

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.