Nanocrystal technology changes the solubility and dissolution rate of insoluble drugs by reducing the particle size to the nanometer level.This technology is not limited by carrier materials and encapsulation rate.It is suitable for a variety of drug delivery routes and easy for industrial production.It has gradually become a cutting-edge hot technology in the international pharmaceutical field to improve the absorption of insoluble drugs and improve their bioavailability.This article introduces the influencing factors and challenges of nanocrystal drugs(NC)in parenteral,ocular,transdermal and pulmonary administration,and focuses on nanocrystal drugs that have been marketed or are still in the preclinical or clinical trial stages of these delivery systems,in order to provide some insight for the further development of poorly soluble drug nanocrystal preparations.

Objective:To compare the short-term efficacy of hip arthroscopic surgery assisted by platelet-rich plasma (PRP) and hip arthroscopy alone in the treatment of femoroacetabular impingement (FAI).Methods:A retrospective cohort study was performed on the clinical data of 133 FAI patients admitted to Fourth Medical Center of PLA General Hospital from January 2019 to January 2021. The patients included 86 males and 47 females, aged 19-71 years [(39.1±12.6)years]. A total of 67 patients were treated with hip arthroscopy alone (hip arthroscopy group), and 66 patients were treated with PRP after hip arthroscopy under ultrasound guidance (hip arthroscopy+PRP group). The two groups were compared before, at 12 months after surgery and at the last follow-up regarding the following items: Visual Analogue Scale (VAS), Modified Harris Hip Score, International Hip Outcome Tool-12 (iHOT-12), and Hip Outcome Score Activities of Daily Living Scale (HOS-ADL). The incidence rate of complications after surgery was compared between the two groups.Results:A total of 108 patients were followed up for 24-36 months [(28.5±3.8)months], while 25 patients were lost to follow-up because of withdrawal of consent, wrong telephone number, etc, including 11 patients (16.4%) in the hip arthroscopy group and 14 patients (21.2%) in the hip arthroscopy+PRP group. The values of VAS in the hip arthroscopy group before, at 12 months after surgery and at the last follow-up were 5.00(5.00, 7.00)points, 3.00(2.00, 3.75)points, and 1.00(0.00, 2.00)points, respectively; the values of Modified Harris Hip Score were 49.00(39.00, 57.00)points, 76.00(69.25, 82.00)points, and 86.00(82.00, 88.00)points, respectively; the values of iHOT-12 were 0.45(0.28, 0.58)points, 0.69(0.58, 0.80)points, and 0.81(0.70, 0.92)points, respectively; the values of HOS-ADL were 0.52(0.42, 0.68)points, 0.87(0.75, 0.93)points, and 0.93(0.86, 0.99)points, respectively. The scores of VAS in the hip arthroscopy + PRP group before, at 12 months after surgery and at the last follow-up were 6.00(5.00, 7.00)points, 3.00(2.00, 3.75)points, and 1.00(0.00, 2.00)points, respectively; the values of Modified Harris Hip Score were 46.50(37.00, 56.75)points, 78.00(72.00, 84.00)points, and 84.50(82.00, 88.00)points, respectively; the values of iHOT-12 were 0.42(0.26, 0.51)points, 0.66(0.58, 0.74)points, and 0.81(0.68, 0.88)points, respectively; the values of HOS-ADL were 0.54(0.38, 0.65)points, 0.87(0.72, 0.96)points, and 0.94(0.86, 1.00)points, respectively. In both groups, VAS, Modified Harris Hip Score, iHOT-12, and HOS-ADL were significantly improved at 12 months after surgery and at the last follow-up compared with those before surgery, and were further improved at the last follow-up compared with those at 12 months after surgery (all P<0.01). There were no significant differences in VAS, Modified Harris Hip Score, iHOT-12 and HOS-ADL between the two groups before, at 12 months after surgery and at the last follow-up (all P>0.05). There was no significant difference in the incidence rates of postoperative hip pain and clicking between the two groups (both P>0.05). Conclusion:Hip arthroscopy can considerably improve short-term hip symptoms and function in FAI patients, but the use of PRP treatment after hip arthroscopy cannot further improve its short-term efficacy in FAI patients.

Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ), a preparation of extract fromthat is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding. The activities of ALT and AST in serum were assessed as well as the level of GSH and the activity of SOD in the liver. The expression of CYP2E1 and proteins in the NRF2-ARE signaling pathway including NRF2, GCLC, GCLM, HO-1 were measured, and the effect of WZ on NRF2 transcriptional activity was determined. We found that both models resulted in liver steatosis accompanied by increased transaminase activities, but that liver injury was significantly attenuated by WZ. WZ administration also inhibited CYP2E1 expression induced by alcohol, and elevated the level of GSH and the activity of SOD in the liver. Moreover, the NRF2-ARE signaling pathway was activated by WZ and the target genes were all upregulated. Furthermore, WZ significantly activated NRF2 transcriptional activity. Collectively, our study demonstrates that WZ protected against alcohol-induced liver injury by reducing oxidative stress and improving antioxidant defense, possibly by activating the NRF2-ARE pathway.

To summarize the clinical experience of Professor WANG Meng-yong in the treatment of uric acid nephropathy. Professor WANG believes that the disease is mainly caused by spleen and kidney deficiency, disorder of function of Sanjiao, and pathological products, such as phlegm dampness and blood stasis and other metabolic disorders. Therefore, the treatment should distinguish symptoms and essence. Starting from pathogenesis and pathological features of spleen and kidney deficiency and phlegm dampness and blood stasis, the treatment should flexibly apply the methods of nourishing spleen and kidney, reducing phlegm and dispelling humidity, and activating blood and using diuretic of hydragogue to alleviate water retention, which can greatly reduce side effects caused by the long-term use of Western medicine and the onset of gout, and then to help disease recovery.

At present,the study of intestinal absorption of oral drugs mainly includes in vitro,in vivo and in situ methods.In view of the advantages of in situ intestinal perfusion such as simple operation,mature technology,controllable,ensure the neuroendocrine regulation and blood supply,and so on,which could better reflect the true situation of drug absorption.In this study,the research methods and characteristics of intestinal absorption of oral drugs were systematically introduced.The recirculating perfusion method and single-pass perfusion method were compared,and several volume correction methods were also introduced.In order to ensure the operability and accuracy of experimental results,proper experiment method of intestinal absorption will be adopt according to the factors such as drug characters,experiment requirements,experimental conditions,and so on.The article provides a scientific basis for the development of pharmaceutical dosage and clinical rational drug use.

Objective Objective To evaluate the efficacy of Heqi San combined with metformin in the treatment of obese polycystic ovary syndrome (PCOS). Methods A total of 60 patients with obese polycystic ovary syndrome who met the inclusion criteria were randomly divided into 2 groups, 30 patients in each group. The control group was treated with metformin, and the treatment group was treated with Heqi San on the basis of the control group. Both groups were treated for 3 months. The FPG was determined by glucose oxidase method, and fasting insulin (FINS), TC, TG, LDL-C, HDL-C level were measured by radio immunoassay, and the insulin resistance index (IR) was measured by the method of HOMA-IR. The luteotropic hormone (LH), pro follicle stimulating hormone (FSH) and testosterone (T) were detected by the automatic electrochemical light detector, and the ratio of LH/FSH was calculated. The ovarian volume and body mass index changes and clinical effect were evaluated. Results After treatment, the BMI (20.09 ± 3.12 kg/cm2 vs. 23.39 ± 1.43 kg/cm2, t=6.889), FPG (4.44 ± 0.17 mmol/L vs. 4.74 ± 0.16 mmol/L, t=6.945), FINS (10.69 ± 2.41 IU/L vs. 16.29 ± 5.95 IU/L, t=4.778), TC (3.91 ± 0.50 mmol/L vs. 4.20 ± 0.39 mmol/L, t=2.505), LDL-C (2.64 ± 0.63 mmol/L vs. 3.18 ± 0.62 mmol/L, t=3.346), LH (8.70 ± 2.44 U/L vs. 10.27 ± 2.69 U/L, t=2.934), the ratio of LH/FSH (1.33 ± 0.58 vs. 2.18 ± 0.56, t=5.775), T (1.73 ± 0.74 nmol/L vs. 2.95 ± 1.10 nmol/L, t=5.040) and ovarian volume (12.61 ± 2.29 mm3 vs. 14.26 ± 2.52 mm3, t=6.982) in the treatment group were significantly lower than those in the control group (P<0.01 or P<0.05). The FSH (7.33 ± 2.28 U/L vs. 5.95 ± 1.20 U/L, t=2.934) in the treatment group were significantly higher than those in the control group (P<0.05). The total effective rate in the treatment group was 83.3% (25/30) and 63.3% (19/30) in the control group. The difference between the 2 groups was statistically significant (χ2=3.068, P=0.050). Conclusions The Heqi San combined with metformin can effectively improve the body mass index, glucose metabolism, lipid metabolism index and sex hormone level, and reduce the volume of ovary in patients with PCOS, and the curative effect is better than that of oral metformin alone.

Mammalian pancreatic β-cells play a pivotal role in development and glucose homeostasis through the production and secretion of insulin. Functional failure or decrease in β-cell number leads to type 2 diabetes (T2D). Despite the physiological importance of β-cells, the viability of β-cells is often challenged mainly due to its poor ability to adapt to their changing microenvironment. One of the factors that negatively affect β-cell viability is high concentration of free fatty acids (FFAs) such as palmitate. In this work, we demonstrated that Yes-associated protein (Yap1) is activated when β-cells are treated with palmitate. Our loss- and gain-of-function analyses using rodent insulinoma cell lines revealed that Yap1 suppresses palmitate-induced apoptosis in β-cells without regulating their proliferation. We also found that upon palmitate treatment, re-arrangement of F-actin mediates Yap1 activation. Palmitate treatment increases expression of one of the Yap1 target genes, connective tissue growth factor (CTGF). Our gain-of-function analysis with CTGF suggests CTGF may be the downstream factor of Yap1 in the protective mechanism against FFA-induced apoptosis.
Actins ; metabolism ; Adaptor Proteins, Signal Transducing ; antagonists & inhibitors ; genetics ; metabolism ; Animals ; Apoptosis ; drug effects ; physiology ; Bridged Bicyclo Compounds, Heterocyclic ; pharmacology ; Cell Line, Tumor ; Connective Tissue Growth Factor ; genetics ; metabolism ; pharmacology ; Cytochalasin D ; pharmacology ; Fatty Acids, Nonesterified ; pharmacology ; HEK293 Cells ; Humans ; Immunohistochemistry ; Insulin-Secreting Cells ; cytology ; drug effects ; metabolism ; Mice ; Microscopy, Fluorescence ; Palmitic Acid ; pharmacology ; Phosphoproteins ; antagonists & inhibitors ; genetics ; metabolism ; RNA Interference ; RNA, Small Interfering ; metabolism ; Rats ; Recombinant Proteins ; genetics ; metabolism ; pharmacology ; Thiazolidines ; pharmacology

Many studies have proven that arsenic trioxide (As2 O3 )as a single agent is not effective against hepatocellular carcinoma (HCC).Many scholars believe that chemotherapy drug resistance of HCC to As2 O3 is the most important reason.The underlying drug resistance mechanism of HCC cells to As2 O3 remains unclear.Studies show that potential mechanism may be tightly associated with As2 O3 pharmacokinetics and properties of HCC tissues and complex molecular biology.

AIM:To explore the change of antithrombin Ⅲ( AT-Ⅲ) in the patients with atherosclerotic cere-bral infarction .METHODS:Chromogenic substrate assay was used to measure the activity of AT-Ⅲ in 55 patients with atherosclerotic cerebral infarction and 55 healthy controls , and the correlation analysis was applied to determine the AT-Ⅲactivity with the severity of damage in central nervous system and general biochemical parameters .The levels of TNF-αand IL-6 in the plasma were detected by ELISA .Immunocomplex in the plasma was measured by enzyme immunoassay (EIA). The number and phenotype of the monocytes in peripheral blood were analyzed by flow cytometry .ELISA was also applied to determine the secretion of TNF-αand IL-6 from the monocytes after the stimulation of immunocomplex .The expression of AT-Ⅲin human brain vascular endothelial cells after the stimulation of TNF-αand IL-6 was observed by Western blotting . RESULTS:The activity of AT-Ⅲsignificantly decreased in the patients with atherosclerotic cerebral infarction , and nega-tively correlated with the damage degree of nervous system function , systolic pressure , diastolic pressure , glucose , choles-terol, triglyceride, low-density lipoprotein cholesterol and homocysteine , while positively correlated with high-density lipo-protein.In addition, the plasma levels of TNF-αand IL-6 increased significantly , accompanied with the enhancement of immunocomplex level .The numbers of CD14 + CD16 + and CD14 + CD32 + monocytes in peripheral blood were not changed , while CD14 +CD64 +monocytes increased obviously .The secretion of TNF-αand IL-6 by monocytes were signifi-cantly enhanced after stimulated with immunocomplex , while the protein expression of AT-Ⅲ in the human brain vascular endothelial cells was down-regulated after co-incubated with TNF-αor IL-6.CONCLUSION:Decreased AT-Ⅲactivity in the patients with atherosclerotic cerebral infarction is one of the risk factors of cerebral infarction , and related with the dis-ease severity .The production of pro-inflammatory cytokines through immunocomplex from CD 14 +CD64 +monocytes may be involved in the mechanism .Improvement of AT-Ⅲactivity may protect against cerebral ischemia .

ObjectiveTo summarize the research and manufacturing ideas of precise positioning instrument and its feasibility and safety in the minimally invasive percutaneous nephrolithotripsy.Methods The precise positioning instrument was preliminarily made by integrating ruler with protractor.Fifty cases of kidney stones or upper ureteral stones were recruited in the study.There were 32 males and 18 females with mean age of 47 years (21 -75 years).Of them,6 cases had open surgery history and 31 cases had different degrees of hydronephrosis.The distance from the mid-point of renal pelvis to the plane of the dorsal surface and the distance from the incident point of the mid-point of pelvis on the dorsal surface to spinous process were measured by ruler on the preoperative CT images.According to the measured results,the point,angle,direction and depth of needle were calculated by geometric formula,and then fix position puncture and percutaneous puncture channel expansion were completed by precise positioning instrument and calibrated by Carm X-ray machine.ResultsThe puncture channels were established successfully in all of the 50 cases.Forty-six cases were punctured successfully by just one try,and the success rate of one puncture only was 92.0％.C-arm was used in none of the cases during the channel establishing process.Each patient was Xrayed 1 -3 times,and the average was 1.4 times.Targeting deflection or renal pelvis injury occurred in none of these cases.ConclusionThe application of the homemade precise positioning instrument is a safe and quick method for the establishment of puncture channel during percutaneous nephrolithotripsy,meanwhile the surgeons can reduce the exposure to radiation.