ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, overshadowing its influence on the biological effects of formulations. In this study, we reevaluated the delivery effect of CH using widely applied lipid microspheres (LM) as a model DDS. We conducted comprehensive investigations into the impact of CH on the distribution, cell uptake, and protein corona (PC) of LM at sites of cardiovascular inflammatory injury. The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage. Then, the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy. Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in vascular endothelial cells and estrogen receptor alpha (ERα) protein levels in myocardial cells, thereby enhancing LM uptake at cardiovascular inflammation sites. Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V (Apoa5); this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites. It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations. The findings enhance the conceptualization of CH and LM delivery, providing novel strategies for investigating prescription factors' bioactivity.

Objective:To improve the understanding of patients with diffuse large B-cell lymphoma (DLBCL) with pulmonary cryptococcosis.Methods:The clinical data of 1 DLBCL patient with pulmonary cryptococcosis in the Central Hospital of Fengxian District of Shanghai in May 2023 were retrospectively analyzed, and the relevant literatures were reviewed.Results:This 75-year-old female patient was asymptomatic after 2 cycles of R-CHOP chemotherapy. The high-resolution CT of lung showed that lung nodules were progressively enlarged. Antibacterial treatment was ineffective. Pulmonary cryptococcosis was confirmed by bronchoalveolar lavage fluid (BALF) targeted high-throughput sequencing (tNGS) and cryptococcus capsular antigen (CrAg) detection. The central nervous system was not involved. And the long-term adequate-dose fluconazole was prescribed for 6 months, and the treatment against lymphoma was given synchronously. The lung nodule lesions reduced after antifungal therapy for 1 month. The lung nodules disappeared after the follow-up of 6 months after completion of final chemotherapy. The evaluation of lymphoma indicated complete remission.Conclusions:Pulmonary cryptococcosis occurs insidiously and shows no specific symptoms; its imaging manifestations are variable and routine anti-infection is ineffective. Immunochemotherapy for lymphoma patients is a high-risk factor for cryptococcal infection. tNGS and CrAg testing for BALF are effective methods of the confirmed diagnosis. The early and long-term adequate-dose antifungal treatment is the key to preventing the recurrence or progression.

Cholesterol(CH)plays a crucial role in enhancing the membrane stability of drug delivery systems(DDS).However,its association with conditions such as hyperlipidemia often leads to criticism,overshadowing its influence on the biological effects of formulations.In this study,we reevaluated the delivery effect of CH using widely applied lipid microspheres(LM)as a model DDS.We conducted comprehensive in-vestigations into the impact of CH on the distribution,cell uptake,and protein corona(PC)of LM at sites of cardiovascular inflammatory injury.The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage.Then,the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy.Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma(PPAR-γ)expression in vascular endothelial cells and estrogen receptor alpha(ERα)protein levels in myocardial cells,thereby enhancing LM uptake at cardiovascular inflam-mation sites.Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V(Apoa5);this may be a major contributing factor to their prolonged circu-lation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites.It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations.The findings enhance the conceptualization of CH and LM delivery,providing novel strategies for investigating prescription factors' bioactivity.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

ObjectiveTo evaluate some properties of scutellarin-phospholipid complex nanoemulsion（SCU-PC-NE）， such as release， cell uptake and tissue distribution， and to investigate its effect on ameliorating lipopolysaccharide（LPS）-induced vascular endothelial injury. MethodSCU-PC-NE was prepared by weighting SCU-PC， ethyl oleate， Kolliphor HS15， 1，2-propylene glycol（50， 400， 514.3， 85.7 mg）， respectively. And the appearance of SCU-PC-NE was observed by transmission electron microscope， the average paticle size and Zeta potential were measured by nanopotential particle size analyzer. The cumulative release of SCU-PC-NE in vitro was measured by dynamic dialysis， thiazolyl blue（MTT） colorimetric assay was used to investigate the effect of SCU-PC-NE on the viability of human umbilical vein endothelial cells（HUVECs）， the inverted fluorescence microscope and flow cytometry were used to investigate cell uptake of HUVECs by SCU-PC-NE in vitro using coumarin 6 as a fluorescent probe， the tissue distribution of DiR/SCU-PC-NE labeled by near infrared fluorescent dyes was obeserved by small animal in vivo imaging system. The inflammation injury model was established by co-incubation with LPS（1 mg·L^-1） and HUVECs， the effect of SCU-PC-NE on the levels of interleukin（IL）-1β and IL-6 were determined by enzyme-linked immunosorbent assay（ELISA）， 18 Kunming male mice were randomly divided into blank group， model group， blank preparation group（equivalent to high dose group）， SCU group and SCU-PC-NE low and high dose groups（5， 10 mg·kg^-1）， 3 mice in each group， and the drug administration groups were administered once in the tail vein at the corresponding dose every 48 h， equal volume of normal saline was given to the blank group and the model group， and the drug was administered for 4 consecutive times. Except for the blank group， the endothelial inflammatory injury was induced by intraperitoneal injection of LPS（10 mg·kg^-1） at 12 h before the last administration in each group. Hematoxylin-eosin（HE） staining was used to investigate the effect of SCU-PC-NE on the histopathological changes in the thoracic aorta of mice. ResultThe appearance of SCU-PC-NE displayed pale yellow milky light， mostly spherical with rounded appearance and relatively uniform particle size distribution， with the average particle size of 35.31 nm， Zeta potential of 7.23 mV， and the encapsulation efficiency of 75.24%. The cumulative release in vitro showed that SCU-PC-NE exhibited sustained release properties compared with SCU. The cell viability of SCU-PC-NE was >90% at a concentration range of 1.05-8.4 mg·L^-1. The results of cellular uptake experiments showed that the cellular uptake ability of SCU-PC-NE was significantly enhanced when compared with the SCU group（P<0.01）. Compared with normal mice， the results of tissue distribution showed that the fluorescence intensity of DiR/SCU-PC-NE was significantly enhanced in the spleen， kidney， brain and thoracic aorta of mice at different time points after intraperitoneal injection of LPS（P<0.05， P<0.01）， especially in thoracic aorta. ELISA results showed that the levels of IL-1β and IL-6 in the model group were significantly increased when compared with the blank group（P<0.05， P<0.01）， and compare with the model group， all administration groups significantly down-regulated IL-1β level， with the strongest effect in the SCU-PC-NE high-dose group（P<0.01）， and all administration groups significantly down-regulated IL-6 level， with the strongest effect in the SCU-PC-NE low-dose group（P<0.05）. Compare with the blank group， the results of HE staining showed that the endothelial cells were damaged， the elastic fibers were broken and arranged loosely in the model group， although similar vascular injury could be observed in the blank preparation group， SCU group and SCU-PC-NE low-dose group， the vascular endothelial damage was significantly reduced in the high-dose group of SCU-PC-NE， which had a better effect than that in the SCU group. ConclusionSCU-PC-NE can promote the uptake of drugs by endothelial cells and effectively enriched in the site of vascular endothelial injury caused by LPS， suggesting that it has a protective effect on vascular endothelial injury and is a good carrier of SCU.

Objective To investigate the correlation of peripheral blood lymphocyte, T-cell, Th-cell, and Ts-cell counts with the development of checkpoint-inhibitor-related pneumonitis in NSCLC. Methods The clinical data of 85 patients with NSCLC treated with immune checkpoint inhibitors (ICIs) were retrospectively analyzed.Paired t-test was used to analyze lymphocyte changes.ROC curves were utilized to analyze predictive performance.The Spearman correlation coefficient test was conducted to analyze the linear relationship between lymphocyte changes and CIP grade. Results A statistically significant decrease in lymphocyte, T-cell, Th-cell, and Ts-cell counts from the baseline was observed in patients at the onset of CIP (P < 0.05), whereas no such change was observed in the control group.ROC curve analysis revealed AUCs of 0.867, 0.843, 0.865, and 0.843 for lymphocyte, T-cell, Th-cell, and Ts-cell counts, respectively.A linear relationship was found between the percentage decrease in lymphocyte, T-cell, and Ts-cell counts from the baseline and the severity of CIP (P < 0.05). Conclusion Decreased lymphocyte, T-cell, Th-cell, and Ts-cell counts have a predictive value for the development of CIP, and the lymphocyte count change has the greatest predictive value.The percentage decrease in lymphocyte, T-cell, and Ts-cell counts from the baseline is correlated with the severity of CIP.

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Objective:To explore the associations of urinary retinol binding protein (RBP) and β 2-microglobulin (β 2-MG) with urinary albumin to creatinine ratio (UACR) and renal function in hospitalized patients with type 2 diabetes mellitus (T2DM). Methods:A total of 1 030 Chinese patients with T2DM were included in this study. The subjects were divided into the UACR normal group (<30 mg/g), microalbuminuria group (30-300 mg/g) and macroalbuminuria group (>300 mg/g). Patients with normal UACR were further divided into two groups according to the estimated glomerular filtration rate (eGFR): the eGFR low group (<90 ml·min -1·1.73m -2) and the normal eGFR group (≥90 ml·min -1·1.73m -2). Urine RBP and β 2-MG levels among the groups were compared. Multiple linear regression analyses were applied to evaluate risk factors of urine RBP and β 2-MG. Results:In all patients ( n=1 030), urine RBP and β 2-MG increased gradually with the increase of UACR across the three groups, the proportions of abnormal urine RBP (>0.7 mg/L) and β 2-MG (>370 μg/L) in these groups were 3.8%, 8.5%, 39.0% ( P<0.001), and 12.9%, 26.7%, 46.8% ( P<0.001), respectively. In the UACR normal group ( n=788), 12.2% of the patients were with eGFR<90 ml·min -1·1.73m -2. The proportion of abnormal β 2-MG (>370 μg/L) was higher in the eGFR low group than that in the eGFR normal group (29.2% vs. 10.7%, P<0.001). Multivariate linear stepwise regression analyses were performed using natural logarithm of urine RBP or β 2-MG as dependent variable, and showed that urine RBP was independently associated with UACR ( β=0.0005, P<0.001), serum creatinine ( β=0.006, P<0.001) and glycosylated hemoglobin A1c ( β=0.050, P=0.001), and β 2-MG was independently correlated with UACR ( β=0.000 4, P<0.001), serum creatinine ( β=0.011, P<0.001), systolic blood pressure ( β=0.005, P=0.031) and fasting blood-glucose ( β=0.027, P=0.046). Conclusions:Urine RBP and β 2-MG are positively associated with high UACR and impaired renal function in T2DM patients, and these changes could occur before UACR and eGFR turned out to be abnormal. It is recommended that urine RBP and β 2-MG be detected as early as possible to identify diabetic kidney disease in patients with normal UACR and eGFR.