Pure drug nanomedicines (PDNs) encompass active pharmaceutical ingredients (APIs), including macromolecules, biological compounds, and functional components. They overcome research barriers and conversion thresholds associated with nanocarriers, offering advantages such as high drug loading capacity, synergistic treatment effects, and environmentally friendly production methods. This review provides a comprehensive overview of the latest advancements in PDNs, focusing on their essential components, design theories, and manufacturing techniques. The physicochemical properties and in vivo behaviors of PDNs are thoroughly analyzed to gain an in-depth understanding of their systematic characteristics. The review introduces currently approved PDN products and further explores the opportunities and challenges in expanding their depth and breadth of application. Drug nanocrystals, drug-drug cocrystals (DDCs), antibody-drug conjugates (ADCs), and nanobodies represent the successful commercialization and widespread utilization of PDNs across various disease domains. Self-assembled pure drug nanoparticles (SAPDNPs), a next-generation product, still require extensive translational research. Challenges persist in transitioning from laboratory-scale production to mass manufacturing and overcoming the conversion threshold from laboratory findings to clinical applications.
Nanomedicine ; Humans ; Nanoparticles/chemistry* ; Pharmaceutical Preparations/chemistry* ; Animals ; Drug Carriers/chemistry*

OBJECTIVE To screen the quality biomarkers of Gnaphalium affine with anti-chronic obstructive pulmonary disease （COPD） effect and determine their contents. METHODS The effective components and targets of “G. affine” with anti- COPD effect were predicted by using network pharmacology as a search criterion. HPLC fingerprints for 10 batches of G. affine were established by using Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition）； common peak identification and similarity evaluation were conducted； cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS-DA） were performed to screen differential components as quality maker that affected the quality of G. affine using variable importance projection （VIP）＞1 as the standard. The same HPLC method was adopted to determine the contents of the differential components in 10 batches of samples. RESULTS A total of 10 flavonoids （such as quercetin， luteolin， and chlorogenic acid） and organic acid components， were identified through network pharmacology search， with 91 targets closely related to anti-COPD. A total of 9 common peaks were identified in 10 batches of samples， with similarity greater than 0.90. Among them， the differential components included chlorogenic acid， caffeic acid， 1，3-O- dicaffeoylquinic acid and apigenin 7-O-β-D-glucopyranoside； S3， S4， S6， S7 and S10 were clustered into one category， S2， S5， S8 and S9 clustered into one category， and S1 clustered into one category. The contents of chlorogenic acid， caffeic acid， 1，3-O- dicaffeoylquinic acid， and apigenin 7-O-β-D-glucopyranoside in 10 batches of G. affine ranged 0.070-7.653， 0.010-0.097， 0.001- 0.036， 0.508-6.627 mg/g， respectively. CONCLUSIONS Chlorogenic acid， caffeic acid， 1，3-O-dicaffeoylquinic acid， apigenin 7- O-β-D-glucopyranoside can serve as the potential quality marker for the anti-COPD effect of G. affine， with the highest content of chlorogenic acid in G. affine produced in Ji’an， Jiangxi province， and the highest content of caffeic acid in G. affine produced in Ji’an， Jiangxi province and Sanming， Fujian province. The contents of the last two components are highest in G. affine produced in Chaoshan， Guangdong province.

Damage to organelles plays a significant role in myocardial ischemia/reperfusion injury,which results in the dysfunction of mitochondria and other related organelles.The communication between mitochondria and other organ-elles can also affect the development of myocardial ischemia/reperfusion injury.For instance,the mitochondria-associated endoplasmic reticulum membrane provides a"seamless connection"and regulates the exchange of organelles and metabolites(such as ions,lipids and proteins)between the mitochondria and the endoplasmic reticulum,which subse-quently affects myocardial ischemia/reperfusion injury.However,there is a lack of studies regarding the interaction be-tween mitochondria and related organelles,which is a critical component in triggering myocardial ischemia/reperfusion inju-ry.Therefore,this article describes the role of mitochondrial crosstalk with endoplasmic reticulum,lysosomes and nuclei in myocardial ischemia/reperfusion injury,and aims to provide a theoretical basis for targeting mitochondrial crosstalk with other organelles in the treatment of myocardial ischemia/reperfusion injury.

Hypertension heightens the risk of cardiovascular and renal complications in individuals with type 2 diabetes mellitus. Optimal blood pressure (BP) management is crucial for preventing these complications. This review consolidates evidence from clinical trials and major BP management guidelines to shed light on key aspects of hypertension management in diabetes. It addresses BP thresholds to initiate antihypertensive treatment, optimal BP control targets, recommended first-line antihypertensive edications, and BP monitoring plan for the prevention of chronic complications in type 2 diabetes.

Objective To investigate the risk factors and clinical characteristics of gastric inflammatory fibroid polyp(GIFP)for gastrointestinal hemorrhage.Methods 66 patients(68 lesions in total)with GIFP diagnosed by endoscopic or surgical resection from January 1,2013 to September 30,2022 were collected.According to the presence or absence of gastrointestinal hemorrhage,the patients were divided into bleeding group(n = 16)and non-bleeding group(n = 50).Collect clinical data on gender,age,clinical manifestations,lesion location and size,endoscopic characteristics,Helicobacter pylori infection,surgical methods and pathological results of each group of patients.Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of endoscopic characteristics of GIFP for gastrointestinal hemorrhage,and summarize the clinical characteristics of GIFP with gastrointestinal hemorrhage,then calculate the rate of correct diagnosis.Results The age of the bleeding group was significantly younger than that of the non-bleeding group,and the lesion size was significantly larger than that of the non-bleeding group,with statistically significant differences(P＜0.05).The incidences of endoscopic neoplasm-like elevation of lesions,surface with erosion or ulceration,accompanied by ballvalve syndrome and ultrasonic gastroscopy with blood flow signals in the bleeding group were significantly higher than those in the non-bleeding group,and the differences were statistically significant(P＜0.05),but there were no statistical differences in other indicators between the two groups(P＞0.05).In order to further investigate the relationship between endoscopic characteristics and gastrointestinal hemorrhage,multivariate Logistic regression analysis showed that neoplasm-like elevation,submucosal eminence,ulcer or erosion on the surface and ball valve syndrome were risk factors for gastrointestinal hemorrhage in GIFP(O(R)＞1,P＜0.05).The overall rate of GIFP correct diagnosis before surgery was 27.94%.The rate of diagnosis in patients echoendoscope before surgery was 38.78%,it was significantly higher than that without undergoing echoendoscope(χ2 = 20.82,P = 0.000).Conclusion The shape of the lesion,presence of ulcers or erosion on the surface,and presence of ball valve syndrome are risk factors for gastrointestinal hemorrhage.Preoperative endoscopic ultrasonography can improve the accuracy of preoperative diagnosis.When there is a risk of gastrointestinal hemorrhage in GIFP,early endoscopic diagnosis and therapeutic resection should be performed to avoid unnecessary surgical procedures,which can improve prognosis and improve patient quality of life.

Objective:To analyze the distribution of pathogenic bacteria in bile culture in patients with common bile duct stones and biliary tract infections, in order to guide clinical optimization of antibiotics application.Methods:From March 30, 2017 to December 31, 2021, at Affiliated Hospital of Qingdao University, 753 patients with common bile duct stones and biliary tract infections and received endoscopic retrograde cholangiopancreatography were selected. Bile samples were obtained for bacterial culture, strain type identification and drug sensitivity test in order to analyze bile pathogenic bacteria distribution, change trend and drug resistance. Chi-square test was used for statistical analysis.Results:From 2017 to 2021, the total positive rate of bile culture in 753 patients with choledocholithiasis complicated with biliary tract infection was 90.17% (679/753). From 2017 to 2021, the positive rates of bile culture were 82.05% (64/78), 88.81% (119/134), 88.03% (125/142), 93.87% (199/212), and 91.98% (172/187), respectively, and the difference was statistically significant ( χ2=10.78, P=0.029). The positive rate of bile culture in 2017 was lower than those in 2020 and 2021, and the differences were statistically significant ( χ2=9.43 and 5.57, P=0.002 and 0.018). There were no significant differences in the positive rates of bile culture among the other years (all P>0.05). A total of 1 033 pathogenic bacteria were detected in the 679 bile specimens with positive bile culture results. Among which the total proportion of Gram-negative bacilli was 57.02% (589/1 033), and from 2017 to 2021 the proportions were 66.38% (77/116), 66.47% (111/167), 59.43% (104/175), 54.75% (173/316), and 47.88% (124/259), respectively. The total proportion of Gram-positive cocci was 41.05% (424/1 033), and from 2017 to 2021 the proportions were 31.90% (37/116), 31.74% (53/167), 38.86% (68/175), 44.30% (140/316), and 48.65% (126/259), respectively. The total proportion of fungus was 1.94% (20/1 033), and from 2017 to 2021 the proportions were 1.72% (2/116), 1.80% (3/167), 1.71% (3/175), 0.95% (3/316), and 3.47% (9/259), respectively. From 2017 to 2021, the proportion of Gram-negative bacilli gradually decreased, while the proportion of Gram-positive cocci gradually increased, and the differences were statistically significant ( χ2=20.14 and 17.91, P<0.001 and =0.001). From 2017 to 2021, the change in the proportion of fungus was not statistically significant ( P>0.05). The main Gram-negative bacilli in the bile culture were Escherichia coli (31.36%, 324/1 033) and Klebsiella pneumoniae (12.68%, 131/1 033); the main Gram-positive cocci were Enterococcus faecalis (14.04%, 145/1 033) and Streptococcus salivarius (4.36%, 45/1 033). From 2017 to 2021, the proportions of Escherichia coli were 39.66% (46/116), 38.92% (65/167), 33.14% (58/175), 28.48% (90/316), and 25.10% (65/259), respectively, with gradual decrease and the difference was statistically significant ( χ2=14.34, P=0.006). From 2017 to 2021 the detection rates of extended-spectrum β-lactamase (ESBL) in Escherichia coli and Klebsiella pneumoniae were 30.43% (14/46), 26.15% (17/65), 29.31% (17/58), 38.89% (35/90), 40.00% (26/65), and 4/15, 20.00% (5/25), 20% (5/25), 24.32% (9/37), and 31.03% (9/29), and there were no significant differences in the detection rates of ESBL between different years (both P>0.05). Conclusions:From 2017 to 2021, the positive rate of bile culture in patients with choledocholithiasis complicated with biliary tract infection showed an overall increasing trend. Gram-negative bacilli were still dominated in bile pathogenic bacteria, while the proportion of Gram-positive cocci remarkably increased, and the bile bacterial spectrum significantly changed. Clinicians should adjust the antibiotic dosing regimens according to the variation of bacterial spectrum and drug resistance.

Objective To comparatively analyze the difference and characteristics of high mobility group box-1 protein(HMGB1) level with the levels in the patients with different severities of acute biliary tract infection (ABTI) to provide reference for its clinical diagnosis and treatment .Methods One hundred cases of ABTI in our hospital were divided into the mild group (48 cases) ,moder-ate group (29 cases) and severe group (23 cases) according to the severity of the disease .The HMGB1 detection results were com-pared among 3 groups and the differences in different disease types ,sex and age were analyzed .Results (1)The HMGB1 level had statistically significant difference among 3 groups (P<0 .05) ,moreover the mild group< moderate group< severe group ;(2)in the detection results ,the HMGB1 level in the mild group and moderate group had no statistical difference between males and fe-males(P>0 .05) ,but in the severe group ,the HMGB1 level in males was significantly higher than that in females (P<0 .05);(3) the HMGB1 level in the mild group had no statistical difference among difference age groups (P> 0 .05) ,while in the moderate group and severe group ,the HMGB1 level in the patients aged > 60 years old was significantly higher than that in the patients aged ≤60 years old(P<0 .05);(4) in the above 3 groups ,the HMGB1 level in the patients with acute cholecystitis was signifi-cantly higher than that in the patients with acute cholangitis (P<0 .05) .Conclusion The study results analysis indicates that the severe the ABTI disease condition ,the serum HMGB1 level is also accordingly and relatively increased ,in the patients with different severity degrees of ABTI ,the serum HMGB1 level has significant differences in age ,sex and disease type ,which prompts that the HMGB1 level can be used as the laboratory index for predicting and reflecting the ABTI severity and can be paid attention to .

Purpose To study the status of EGFR mutations and the expression of excision repair cross-complementation group 1 ( ER-CC1) and Ki-67 protein in patients with non-small cell lung cancer (NSCLC) and to examine the relationship between their expression and clinicopathologic features. Methods EGFR mutations were analyzed with DNA sequencing, and the expression of ERCC1 and Ki-67 protein was examined by immunohistochemistry EnVision. The relationship of EGFR mutations with the expression of ERCC1and Ki-67 and the clinicopathological features were analyzed. Results EGFR mutations were detected in 143 (143/291, 49. 1%) of the 291 specimens. EGFR mutations were found more frequently in women, non-smokers and adenocarcinoma. The difference of EGFR muta-tion rate between the histological subtypes according to the IASLC/ATS/ERS classification of lung adenocarcinoma was significantly ( P=0. 008). The mean tumor diameter was smaller in patients with EGFR mutations than in those with wild-type EGFR (P=0. 020). EGFR mutations were not related to age, lymph node metastasis. However, EGFR mutations were not related to the expression of ER-CC1 and Ki-67 protein (P>0. 050). Conclusions EGFR mutation is closely linked to several clinicopathological factors, such as gender, differentiation, and histological subtype. There is heterogeneity of EGFR mutation in patients with NSCLC. EGFR mutations were not related to the expression of ERCC1 and Ki-67 protein.

Objective To investigate the fear and attitude of the common people to some threatening diseases .Methods Accord-ing to the age and sex structure of the whole nation ,500 common people were randomly enrolled in the public places of Chongqing main urban area .Firstly ,the respondents were asked to name three diseases they feared most .Then their fear degrees to eight im-portant diseases were performed the questionnaire survey .Results The top ten diseases that common people fear most by their own words were cancer ,AIDS ,heart disease ,hypertension ,stroke ,leukemia ,chronic liver diseases ,diabetes mellitus ,dementia and de-pression successively .Meanwhile ,their fear to the eight important diseases ,which was determined by the ratio of people who did fear to all ,were cancer(94 .2% ) ,traffic accidents(89 .2% ) ,heart disease(85 .0% ) ,AIDS(79 .4% ) ,tuberculosis(76 .8% ) ,hepatitis B(76 .6% ) ,Alzheimer′s disease(73 .4% ) and depression(69 .0% ) .Further analysis showed that such fear was significantly influ-enced by age ,sex and education level .Conclusion The knowledge and perception of common people about certain diseases is one-si-ded ,and their health awareness should be improved .