Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria (2024), with the hope of promoting the standardization of PNH diagnosis and treatment.

Targeted drug delivery is constantly updated with a better understanding of the physiological and pathological features of various diseases. Depending on high safety, good compliance and many other undeniable advantages, attempts have been undertaken to complete an intravenous-to-oral conversion of targeted drug delivery. However, oral delivery of particulates to systemic circulation is highly challenging due to the biochemical aggressivity and immune exclusion in the gut that restrain absorption and access to the bloodstream. Little is known about the feasibility of targeted drug delivery via oral administration (oral targeting) to a remote site beyond the gastrointestinal tract. To this end, this review proactively contributes to a special dissection on the feasibility of oral targeting. We discussed the theoretical basis of oral targeting, the biological barriers of absorption, the in vivo fate and transport mechanisms of drug vehicles, and the effect of structural evolution of vehicles on oral targeting as well. At last, a feasibility analysis on oral targeting was performed based on the integration of currently available information. The innate defense of intestinal epithelium does not allow influx of more particulates into the peripheral blood through enterocytes. Therefore, limited evidence and lacking exact quantification of systemically exposed particles fail to support much success with oral targeting. Nevertheless, the lymphatic pathway may serve as a potentially alternative portal of peroral particles into the remote target sites via M-cell uptake.

SARS-CoV-2 infection can lead to rhabdomyolysis and even acute kidney injury, which is rare in clinical practice. The paper reports a case of SARS-CoV-2 infection with clinical manifestations of fever, myalgia, soy urine, oliguria, and significantly increased serum creatine kinase and creatinine. The symptoms improved and renal function returned to normal after hemodialysis, fluid replenishment and liver protection treatment. The paper summarizes the clinical characteristics and pathogenesis of the disease based on literature review.

Objective:To explore the level of tibial growth plate chondrocyte mitophagy in young rats with chronic renal failure (CRF) and its effect on chondrocyte apoptosis.Methods:Male 4-week-old Sprague-Dawley rats were randomly divided into two groups according to random number table method: normal control group ( n=20, intragastric administration with distilled water) and CRF group ( n=20, given adenine suspension 150 mg·kg -1·d -1). All the young rats were sacrificed after continuous gavage for 6 weeks. The length of tibia was measured on X ray film, the width of tibia growth plate was measured and compared on histological section, and the apoptosis rate of chondrocytes in growth plate was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. The growth plate chondrocytes of two groups were isolated and cultured to the third generation in vitro, and the apoptosis rate of chondrocytes was detected by TUNEL assay. The co-localization of mitochondria and autophagy lysosomes in chondrocytes was observed by double fluorescence staining. Western blotting was used to detect the level of mitochondrial marker protein translocate of the outer mitochondrial membrane-20 (Tom-20) and autophagy marker light chain-3 protein (LC-3). The mitophagy of growth plate chondrocytes was observed by transmission electron microscope. Results:Compared with the normal control group, the tibia length of CRF group was shorter [(27.32±5.81) mm vs (35.43±3.61) mm, t=5.226, P<0.001], and the relative width of growth plate in histological section was narrower (0.56±0.19 vs 1.00±0.21, t=6.744, P<0.001). The apoptosis rate of chondrocytes in growth plate in CRF group was higher than that in the normal control group (17.2%±4.8% vs 5.1%±3.4%, t=6.505, P<0.001). The apoptosis rate of chondrocytes cultured in vitro in CRF group was higher than that in the normal control group (11.8%±6.2% vs 3.1%±1.2%, t=4.357, P<0.001). The result of double influorescence staining showed that there was co-localization between mitochondria and autophagy lysosomes in CRF group. Western blotting results showed that the levels of LC-3 protein ( t=8.944, P<0.001) and Tom-20 protein ( t=6.708, P<0.001) in CRF group were lower than those in the normal control group. Conclusion:The level of tibial growth plate chondrocyte mitophagy in young rats with CRF increases, which will lead to a decrease in the number of mitochondria, an increase in the apoptosis and a decrease in the number of chondrocytes, and eventually lead to dysplasia of tibia.

Abdominal aortic aneurysm (AAA) and atherosclerosis (AS) have considerable similarities in clinical risk factors and molecular pathogenesis. The aim of our study was to investigate the differences between AAA and AS from the perspective of metabolomics, and to explore the potential mechanisms of differential metabolites via integration analysis with transcriptomics. Plasma samples from 32 AAA and 32 AS patients were applied to characterize the metabolite profiles using untargeted liquid chromatography-mass spectrometry (LC-MS). A total of 18 remarkably different metabolites were identified, and a combination of seven metabolites could potentially serve as a biomarker to distinguish AAA and AS, with an area under the curve (AUC) of 0.93. Subsequently, we analyzed both the metabolomics and transcriptomics data and found that seven metabolites, especially 2'-deoxy-D-ribose (2dDR), were significantly correlated with differentially expressed genes. In conclusion, our study presents a comprehensive landscape of plasma metabolites in AAA and AS patients, and provides a research direction for pathogenetic mechanisms in atherosclerotic AAA.

Objective:To investigate the short-term therapeutic effect and long-term survival of multiple myeloma patients with extramedullary disease (EMD) in the new drug era.Methods:The data of 74 patients with multiple myeloma diagnosed and treated in Anhui Wanbei Coal and Electricity Group General Hospital from January 2015 to January 2020 were retrospectively analyzed, including 17 patients with soft tissue infiltration (EM-S), 9 patients with bone infiltration (EM-B), and 48 patients without EMD (No-EMD). The short-term efficacy, the 4-year progression-free survival (PFS) rate and overall survival (OS) rate, and their influencing factors in three groups of patients after receiving bortezomib regimen were analyzed.Results:After 3-4 courses of early induction therapy of bortezomib regimen, the overall response rate of patients in the EM-S group was lower than that in the No-EMD group and the EM-B group [58.8% (10/17) vs. 85.4% (41/48), 100.0% (9/9)], and the differences were statistically significant ( χ2 = 13.7, P = 0.036; χ2 = 26.5, P = 0.003), while the difference between No-EMD group and EM-B group was not statistically significant ( χ2 = 12.7, P = 0.211). Survival analysis showed that the 4-year PFS rate of No-EMD group was higher than that of the EM-S group and EM-B group (41.0% vs. 7.6%, 0), and the differences were statistically significant ( χ2 = 10.835, P < 0.01; χ2 = 8.276, P = 0.004). Meanwhile, the 4-year OS rate of EM-S group was lower than that of the No-EMD group and EM-B group (16.5% vs. 54.3%, 59.3%), and the differences were statistically significant ( χ2 = 9.146, P = 0.002; χ2 = 4.066, P = 0.044). Conclusion:The early treatment effect of bortezomib regimen, PFS and OS in multiple myeloma patients with EM-S are poor, while the EM-B has no effect on OS.

Objective:To summarize the surgical treatment of malignant carotid body tumor (MCBT).Methods:A retrospective analysis of 14 MCBT patients admitted at our hospital from Mar 2005 to Nov 2019 was made, and the imaging data, surgical records, perioperative complications and follow-up data were collected.Results:There were 8 males and 6 females, with an average age of (40.8±11.3) years. 10 patients underwent surgical resection of CBT, with one case undergoing tumor enucleation only, nine cases underwent internal carotid artery reconstruction, and all patients underwent intraoperative lymph node biopsy.Tumors were completely removed in all 10 patients. No perioperative death or cerebral infarction occurred. The intraoperative blood loss was (955±658.5) ml. Four patients had permanent nerve injury after surgery. The follow-up time ranged 1-132 months. There were no cases of cerebral infarction or death, and the reconstructed graft remained patent. Apart from the 2 patients who developed tumor metastasis after surgery, other patients recovered uneventfully with no disease progression.Conclusions:Surgery is still the main treatment for MCBT, but MCBT is large and Shamblin class is more advanced. Therefore, complete tumor removal and reconstruction of the carotid arteries are difficult. Surgery should seek to completely remove the tumor and neck lymph node biopsy should be performed to determine the lymph node metastasis.

Objective To observe the regulation of lumbrukinase on the expression of α-smooth muscle actin,fibronectin,focal adhesion kinase and Src kinase induced by transforming growth factor β1 in human renal tubular epithelial cells.Methods According to random number table method,the human renal tubular epithelial cells were divided into the normal group,TGF-β1 model group,benazepril group,lumbrukinase low,medium and high dose group.Except the normal group,the other groups were treated with TGF-β1 10 μg/ml.After 30 minutes,the benazepril group added benazepril 10 μmol/L,and the low,medium,high dose groups of lumbrukinase were respectively treated with lumbrokinase 30,60,120 U/ml to intervene.After 24 hours of cultivation.Western blotting and real-time PCR were used to detect the expression of α-SMA,FN,FAK and Src.Results Compared with the model group,the expressions of α-SMA (0.84 ± 0.14,0.72 ± 0.08,0.69 ± 0.05 vs.1.24 ± 0.03) and FN (0.59 ± 0.09,0.55 ± 0.11,0.44 ± 0.08 vs.0.83 ± 0.18) and FAK (0.94 ± 0.04,0.79 ± 0.05,0.70 ± 0.02 vs.1.29 ± 0.07) and Src (0.87 ± 0.20,0.78 ± 0.15,0.71 ± 0.11 vs.1.23 ± 0.01) proteins in the high doses of lumbrical kinase group were significantly lower than those in the model group (P＜0.05),the expressions of α-SMA (3.13 ± 0.62,2.76 ± 0.14,2.15 ± 0.33 vs.4.12 ± 0.32) and FN (3.08 ± 0.34,2.78 ± 0.17,2.49 ± 0.11 vs.4.34 ± 0.06) and FAK (1.73 ± 0.23,1.63 ± 0.36,1.57 ± 0.27 vs.2.61 ± 0.59) and Src (2.11 ± 0.17,1.78 ± 0.25,1.71 ± 0.22 vs.2.78 ± 0.47) mRNA in the high doses of lumbrical kinase group decreased significantly (P＜0.05).Conclusions Lumbrokinase may prevent the development of renal fibrosis by regulating the expression ofFN,FAK and and reducing the production of α-SMA,FN.

Objective To evaluate the effect of propofol on high-mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4) signaling pathway during hepatic ischemia-reperfusion (I/R) injury in rats.Methods Thirty-six clean-grade healthy male Sprague-Dawley rats,aged 3 months,weighing 250 -300 g,were divided into 3 groups (n=12 each) using a random number table method:sham operation group (group S),hepatic I/R group (group I/R) and propofol group (group P).Hepatic I/R injury was induced by occluding the portal vein and hepatic artery supplying the left and middle lobes of the liver for 1 h followed by 6-h reperfusion in anesthetized rats.Propofol was infused via the tail vein at a rate of 12 mg ·kg-1 · h-1 starting from 20 min before ischemia until 6 h of reperfusion in group P.The rats were sacrificed at 6 h of reperfusion,and the left lobe of the liver was removed for microscopic examination of the pathological changes which were scored and for determination of the expression of HMGB1,TLR4,tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-6) in liver tissues (by Western blot).Results Compared with group S,pathological scores of liver tissues were significantly increased,and the expression of HMGB1,TLR4,TNF-α and IL-6 was up-regulated in I/R and P groups (P＜0.05).Compared with group I/R,pathological scores of liver tissues were significantly decreased,and the expression of HMGB1,TLR4,TNF-α and IL-6 was down-regulated in group P (P＜ 0.05).Conclusion The mechanism by which propofol reduces liver I/R injury is associated with blocking HMGB-1/TLR4 signaling pathway and inhibiting inflammatory responses in rats.

Objective To determine the incidence and clinical features of headache after carotid endarterectomy (CEA).Methods A retrospective analysis was made on the data of patients undergoing CEA in the Department of Vascular Surgery,Peking Union Medical College Hospital from Jan 2014 to Jan 2015.There were 119 males and 24 females,including 97 cases of symptomatic carotid stenosis and 110 cases of severe carotid stenosis.Results The incidence of newly emergent headache after surgery was 44％ (63/143).The earliest time of headache was 30 minutes after surgery and the latest was 6 days after surgery.95％ of headache occurred within 48 hours after surgery (60/63).79.4％ (50/63) of the headache lay ipsilaterally with CEA,and bilateral headache accounted for 20.6％ (13/63).Severe headache accounted for 4.8％ (3/63),all were ipsilaterally frontal and temporal headache,complicating central nervous system symptoms.Conclusions After CEA headache is a common clinical symptom.Most were mild to moderate and unilateral,which can be relieved spontaneously.Cerebral hemodynamics need to be further examined to differentiate the different pathological states of severe headache on the operative side after CEA because of the high risk of developing hyperperfusion syndrome or cerebral infarction.History of TIA or stroke is the risk factor of post-CEA headache.