The development of nano drug delivery systems (NDDSs) provides new approaches to fighting against diseases. The NDDSs are specially designed to serve as carriers for the delivery of active pharmaceutical ingredients (APIs) to their target sites, which would certainly extend the benefit of their unique physi-cochemical characteristics, such as prolonged circulation time, improved targeting and avoiding of drug-resistance. Despite the remarkable progress achieved over the last three decades, the understanding of the relationships between the in vivo pharmacokinetics of NDDSs and their safety profiles is insufficient. Analysis of NDDSs is far more complicated than the monitoring of small molecular drugs in terms of structure, composition and aggregation state, whereby almost all of the conventional techniques are inadequate for accurate profiling their pharmacokinetic behavior in vivo. Herein, the advanced bio-analysis for tracing the in vivo fate of NDDSs is summarized, including liquid chromatography tandem-mass spectrometry (LC-MS/MS), F(o)rster resonance energy transfer (FRET), aggregation-caused quench-ing (ACQ) fluorophore, aggregation-induced emission (AIE) fluorophores, enzyme-linked immunosor-bent assay (ELISA), magnetic resonance imaging (MRI), radiolabeling, fluorescence spectroscopy, laser ablation inductively coupled plasma MS (LA-ICP-MS), and size-exclusion chromatography (SEC). Based on these technologies, a comprehensive survey of monitoring the dynamic changes of NDDSs in struc-ture, composition and existing form in system (i.e. carrier polymers, released and encapsulated drug) with recent progress is provided. We hope that this review will be helpful in appropriate application methodology for investigating the pharmacokinetics and evaluating the efficacy and safety profiles of NDDSs.

Objective To observe the change rules of expressions of IL-1β, IL-4, IFN-γ and TGF-β1 in serum and colon tissue in rats with ulcerative colitis of spleen-kidney yang deficiency type; To explore the action in the progress of ulcerative colitis of spleen-kidney yang deficiency type.MethodsComposite method was used to establish rat models with ulcerative colitis of spleen-kidney yang deficiency type. 75 Wistar rats were randomly divided into blank group, model 3 d group, model 7 d group and model 21 d group. ELISA was used to test the levels of IL-1β, IL-4, IFN-γ and TGF-β1 in serum and colon tissue.Results Compared with the blank group, contents of IL-1β and IFN-γ in model group increased significantly (P<0.05,P<0.01), and the contents of IL-4 and TGF-β1 content decreased (P<0.05,P<0.01),especially in the model 7 d group (P<0.01).ConclusionThe pro-inflammatory factor IL-1β, IFN-γ and anti-inflammatory factor IL-4 and TGF-β1 play an important role in rats with ulcerative colitis of spleen-kidney yang deficiency type.

Objective To observe the effects of Sishen Pills on gene and protein expressions of toll-like receptor 2 (TLR-2) and toll-like receptor 4 (TLR-4) of colonic tissue in spleen-kidney yang deficiency rats with ulcerative colitis (UC); To discuss its mechanism of action for spleen-kidney yang deficiency UC. Methods Lavage of senna +intraperitoneal injection of hydrocortisone injection + enema of 2,4,6-trinitrobenzene sulfonic acid/ethanol were used to establish the model of UC of spleen-kidney yang deficiency type. 90 Wister rats were randomly divided into blank group, model group, Salazosulfadimidine group and the Sishen Pills high-, medium- and low-group. Each medication group was intervened by relevant medicine. RT-qPCR was used to detect the expressions of TLR-2 and TLR-4, and Western blot was used to detect the protein expressions of TLR-2 and TLR-4. SOD and MDA in serum were detected. Results Compared with the blank group, SOD activity decreased and MDA content increased in the model group (P<0.01); gene and protein expressions of TLR-2 and TLR-4 increased significantly (P<0.05). Compared with model group, SOD increased and MDA content decreased in all the medication groups (P<0.05, P<0.01); gene and protein expressions of TLR-2 and TLR-4 decreased (P<0.05, P<0.01). Conclusion Sishen Pills can achieve the treatment of UC by improving the metabolism of oxygen radicals in colonic tissue and regulating the immune system of the intestinal epithelium.

AIM:To observe the effects of Liangxue-Jiedu (LXJD) prescription, a Chinese medicine, on the expression of CC chemokine ligand 20 ( CCL20 ) and CC chemokine receptor 6 ( CCR6 ) in imiquimod-induced psoriasis-like skin lesions in a mouse model .METHODS: Male BALB/c mice were randomly divided into control group , model group, LXJD treatment group and chemokine CCL 20 monoclonal antibody treatment group .The mouse model of psoriasis was induced by imiquimod .The severity of psoriasis was assessed by the dermatologists using psoriasis area and severity in -dex (PASI).The morphological changes of the skin tissues were observed under light microscope .The thickness of epider-mis was measured .Real-time PCR was used to detect the expression of CCL 20 and CCR6 in the skin tissue samples .RE-SULTS:The skin in model group showed a large number of scales , erythema and skin thickening .Compared with model group, the skin lesion in LXJD treatment group was attenuated .The erythema and scales were alleviated , the PASI score was reduced , and the expression of CCL 20 and CCR6 was significantly lower than that in model group .CONCLUSION:LXJD prescription down-regulates the expression of CCL 20/CCR6, thus attenuating the psoriasis skin lesions in mice .

Objective To explore the effect of glial cells on cerebral neuron damage induced by amyloid beta protein (Aβ) in Alzheimer′s disease rat .Methods 20 male Wistar rats were randomly divided into the control group and the model group ,10 cases in each group The gel state Aβ(10μg) was injected into the rat′s bilateral hippocampus in the model group ,while the control group was injected with normal saline ;the Morris water maze test was performed to assess the rat′s learning and memory ability ;the thio‐nine stain was used for observing the morphology and quantity of cerebral cortex neurons ;the enzyme linked immunosorbent assay (ELISA) was adopted to detect the serum tumor necrosis factor alpha (TNF‐α) and interleukin 1 beta(IL‐1β) levels ;the immuno‐histochemical was used to detect the expression of glial cell and glial fibrillary acidic protein (GFAP) .Results The various indexes in the model group were significantly lower than those in the control group(P<0 .05);the quantity of cerebral cortex neurons in the model group was significantly decreased compared with that in the control group (P<0 .01);the ELISA results showed that the lev‐els of TNF‐αand IL‐1βin the model group were significantly higher than those in the control group(P<0 .05);the immunohisto‐chemistry showed that the number of GFAP positive cells in the hippocampus in the model group was significantly more than that in the control group(P<0 .05) .Conclusion Aβmight activate the glial cells and promote the release of inflammatory cytokines ,which causes the damage of rat cerebral neurons and leads to decrease the rat′s learning and memory ability .

Objective To investigate the protective effect of IL-37 on hepatocyte injury against hypoxia/reoxygenation (H/R) by promoting polarization of M2-type macrophages and its molecular mechanisms.Methods Real-time fluorescent quantitative PCR (qRT-PCR) and Western blot were used to detect the levels of IL-37 mRNA and protein in human monocyte-macrophage THP-1 cells with different polarizations.The lentivirus with IL-37 gene was infected into THP-1 cells.The levels of CD206,CD86,ARG1 and iNOS mRNA was detected by qRT-PCR.The levels of CD163 and CD86 protein was detected by flow cytometric analysis.THP-1 cells and L02 cells were co-cultured by Transwell and treated with H/R.The survival rate and apoptotic rate of L02 cells were detected.The levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) in culture medium were measured.The levels of STAT6 and its phosphorylation in THP-1 cells were detected by Western blot.Results The levels of IL-37 mRNA and protein were up-regulated in M2-type macrophages.IL-37 promoted the polarization of M2-type macropahges.M2-type macrophages induced by IL-37 were cocultured with L02 cells,the survival rate was significantly increased by H/R treatment (P =0.015),while the apoptotic rate,ALT level and AST level were significantly decreased (P＜0.001).The level of phosphorylated STAT6 in THP-1 cells overexpressing IL-37 was up-regulated (P ＜ 0.01).Conclusions IL-37 can induce polarization of M2-type macrophages and protect hepatocyte injury against H/R.Its mechanism may be related to STAT6 signal pathways.

Objective: To investigate the status and identify the influencing factors of smoking among residents in Shaoxing City, Zhejiang Province, so as to provide insights into tobacco control. Methods: Permanent residents aged 15 to 69 years in Shaoxing City were recruited using the stratified multistage random sampling method from June to December 2022, and smoking behaviors and health literacy were collected using the National Questionnaire for Surveillance on Healthy Literacy in Chinese Residents. Factors affecting smoking were identified using a multivariable logistic regression model. Results: Totally 4 156 questionnaires were allocated, and 4 055 valid questionnaires were recovered, with an effective recovery rate of 97.57%. There were 1 899 men (46.83%), 2 073 residents in rural areas (51.12%), and 3 256 married residents (80.30%). There were 805 smokers, and the rate of smoking was 19.85%. Multivariable logistic regression analysis showed that male (OR=169.861, 95%CI: 92.335-312.481), age (25-<35 years, OR=8.768, 95%CI: 2.964-25.937; 35-<45 years, OR=9.271, 95%CI: 3.077-27.933; 45-<55 years, OR=10.467, 95%CI: 3.498-31.327; 55-<65 years, OR=8.880, 95%CI: 2.964-26.608; 65-69 years, OR=6.115, 95%CI: 1.992-18.774), marital status (divorced, OR=2.035, 95%CI: 1.260-3.287; widowed, OR=2.317, 95%CI: 1.337-4.016), educational level (illiterate or semi-literate, OR=2.724, 95%CI: 1.515-4.898; primary school, OR=2.734, 95%CI: 1.823-4.100; junior high school, OR=2.003, 95%CI: 1.423-2.820; high school/vocational high school /technical secondary school, OR=1.625, 95%CI: 1.148-2.299), self-rated health status (general, OR=0.788, 95%CI: 0.623-0.996; relatively poor, OR=0.343, 95%CI: 0.191-0.617) and lack of basic health skills (OR=1.290, 95%CI: 1.007-1.653) were associated with smoking. Conclusions The smoking rate among residents in Shaoxing City is relatively low, and might be influenced by gender, age, marital status, educational level, self-rated health status, and basic health skills.

Objective:To study the effect of Jianpi Qinghua Recipe ( JPQHR) on angiotensin II/NADPH oxidase pathway in 5/6 nephrectomized rat renal failure model and the underlying mechanisms.
Methods:The animals were divided into 4 groups:the sham-operated group, the renal failure group, the JPQHR-treated group and the losartan-treated group. After 60-days therapy, serum nitrogen and creatinine were measured. The expression of angiotensin II type 1 receptor (AT1) protein and the expression of p47phox mRNA in renal tissue was determined. SOD and MDA were also examined.
Results:Compared with the sham-operated group, the levels of SCr and serum BUN and the AT1 protein and p47phox mRNA expression in the renal failure group were significantly increased. hTe activities of SOD in renal tissue from the renal failure group was signiifcantly down-regulated while MDA was up-regulated (P<0.05). Compared with the renal failure group, the levels of SCr and serum BUN and the AT1 protein and p47phox mRNA expression in both JPQHR-treated group and losartan-treated group were signiifcantly decreased. hTe activities of SOD in renal tissue from JPQHR-treated group and losartan-treated group were signiifcantly up-regulated whereas the content of MDA were down-regulated (P<0.05). Compared with the losartan-treated group, the activities of SOD in renal tissue from the JPQHR-treated group was obviously increased (P<0.05), the decrease in AT1 protein and p47phox mRNA was more evident but not statistically different (P>0.05). The level of SCr and serum BUN and the content of MDA were also not statistically different (P>0.05).
Conclusion:hTrough decrease the expression of angiotensin II and NADPH oxidase, JPQHR can reduce the oxidative stress in chronic renal failure and delay the renal ifbrosis progression.

ObjectiveIn order to investigate anti-ageing mechanisms of the notoginsenoside Rg1,we used Aβ_(1-42) and D-galactose to establish aging rat model. Methods Ninety rats were divided into three groups at random: sham group, model group, treatment group. Aging rat models were established by injecting peritoneally D-galactose (100 mg/kg) to the rats for 56 days and after 35 days aggregated Aβ_(1-42)(μg) was injected to the right lateral ventricle of rats. Meantime, rats were treated by intragastric administration the notoginsenoside Rg1. Then spatial memory of experimental rats was examined with the Morris water maze(MWM). The thiol antioxidants including glutathione reductase (GR) and glutathione peroxidase (GSH-Px) activities were examined by colorimetric method. The concentration of the pro-caspase-3 and Bcl-2 were examined by the immunohistochemistry and Western blotting method. Results In aging model rats escape latercies were significantly prolonged (P<0.05), while decreases were seen in the time of staying the third quadrants of platform, the number of crossing over a platform, the concentration of the GR, GSH-Px, and pro-caspase-3 as compared with the sham group(P<0.05). After treatment of the notoginsenoside Rg1, the aging model rats exhibited significant increases in the time of staying the third quadrants of platform, the number of crossing over a platform, the concentration of the GR, GSH-Px, and pro-caspase-3(P<0.05), while a decrease was observed in escape latercies as compared to control group(P<0.05). Moreover there was no significant difference in the expression of the Bcl-2(P>0.05). Conclusion The results from our study indicate that the notoginsenoside Rg1 could improve the oriented learning and memory capacity and prevent the neurodegeneration of central nervous systems in aging model rats by up-regulating the expression of the thiol antioxidants(including GR and GSH-Px) and resisting the cleavage of the pro-caspase-3.

Objective To analyze mutations in the PTCH1 gene in a pedigree with nevoid basal cell carcinoma syndrome (NBCCS).Methods Blood samples were collected from a 58-year-old male proband with NBCCS (Ⅱ 5),his brothers (Ⅱ 1 and Ⅱ 3) and son (Ⅲ4),and 50 unrelated healthy human controls.DNA was extracted from these blood samples.PCR and direct DNA sequencing were performed to determine mutation sites in the PTCH1 gene.According to the mutation sites,allele-specific oligonucleotide primers were designed and used to confirm the pathogenic mutations in this pedigree through PCR.Results A nonsense mutation (c.2137C),which leads to the substitution of CAG by TAG with the generation of a premature termination codon (Q714X),was identified in exon 14 in one allele of the PTCH1 gene in the proband and his son,but in none of the healthy human controls.Conclusion The nonsense mutation (c.2137C ＞ T) in the PTCH1 gene may be a specific mutation causing the clinical symptoms in the patient with NBCCS.