The S1P1 regulator IMMH002 and its therapeutic effect and mechanism on autoimmune hepatitis / 药学学报

This study assessed and explored the pharmacological effects and mechanisms of action of IMMH002 {2-amino-2-(2-(4ʹ-(2-ethyloxazol-4-yl)-[1,1ʹ-biphenyl]-4-yl)ethyl)propane-1,3-dio}, a selective sphingosine-1-phosphate receptor subtype 1 (S1P1) modulator, in a concanavalin A (ConA)-induced autoimmune hepatitis (AIH) mouse model. The experimental protocol strictly adhered to the guidelines of the Ethics Committee for Animal Research of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (Approval No.: 00004046). Male ICR mice were pre-treated with the drug for four days, followed by induction of AIH through tail vein injection of ConA protein. Liver function, hepatic tissue pathology, peripheral blood parameters, as well as immunoglobulin G (IgG), inflammatory cytokines, T cell distribution, and inflammatory pathways were evaluated in mice. Results demonstrated that IMMH002 significantly reduced liver function indicators such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alleviated hepatic tissue inflammation and necrotic damage, decreased serum IgG levels, and lowered the expression of inflammatory mediators including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ). Additionally, it facilitated T lymphocyte homing, downregulated the phosphorylation of nuclear factor kappa-B (NF-κB), IκB kinase β (IKKβ) and nuclear factor inhibitor protein-α (IκBα) proteins in hepatic tissue and cellular inflammation models. Collectively, IMMH002 effectively ameliorated ConA-induced autoimmune hepatitis in mice, exhibiting extensive anti-inflammatory and anti-necrotic effects, thereby laying a theoretical foundation for AIH clinical treatment.

Ferroptosis in Treatment of Liver Fibrosis with Chinese Medicine： A Review / 中国实验方剂学杂志

Hepatic fibrosis characterized by various chronic liver injuries can lead to abnormal activation of hepatic stellate cells， unbalanced production and degradation of extracellular matrix proteins， and excessive deposition that destroys the normal structure of the liver. The aggravated liver fibrosis can cause irreversible cirrhosis and hepatocellular carcinoma， becoming a great challenge to the global health. Ferroptosis is a new form of iron-dependent cell death discovered in recent years， which mainly involves abnormal iron metabolism， lipid peroxide accumulation， and weakening of the antioxidant defense system. A number of studies have reported that inducing ferroptosis in hepatic stellate cells or alleviating ferroptosis in the liver can ameliorate liver fibrosis and reduce liver injury. Chinese medicine widely applied in the treatment of chronic liver diseases has demonstrated good safety， wide therapeutic effects， and easy access compared with Western medicine. Therefore， The intervention of hepatic stellate cells or hepatic ferroptosis by Chinese medicine may be a new direction for the prevention and treatment of liver fibrosis in the future. This paper summarized the various regulatory mechanisms of ferroptosis and expounded how ferroptosis affected the progression of liver fibrosis， providing theoretical support for the prevention and treatment of liver fibrosis with Chinese medicine in the future.

Involvement of Interleukin-1 β/Insulin-Like Growth Factor 1 in Ameliorating Effects of Electroacupuncture on Myocardial Fibrosis Induced by Essential Hypertension / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of electroacupuncture (EA) at Neiguan (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHRs), and to explore the contribution of interleukin-1 β (IL-1 β), insulin-like growth factor 1 (IGF-1), and transforming growth factor β 1 (TGF- β 1) to the effects.@*METHODS@#Nine 12-weeks-old Wistar Kyoto (WKY) male rats were employed as the normal group. Twenty-seven SHRs were equally randomized into SHR, SHR+EA, and SHR + sham groups. EA was applied at bilateral PC 6 once a day 30 min per day in 8 consecutive weeks. After 8-weeks EA treatment at PC 6, histopathologic changes of collagen type I (Col I), collagen type 1 (Col 1) and the levels of IGF-1, 1L-1 β, TGF- β 1, matrix metalloproteinase (MMP)-2 and MMP-9 were examined in myocardial tissure respectively.@*RESULTS@#After 8-weeks EA treatment at PC 6, the enhanced myocardial fibrosis in SHRs were characterized by the increased mean fluorescence intensity of Col I and Col 1 in myocardium tissue (P<0.01). All these abnormal alterations above in SHR + EA group was significantly lower compared with the SHR group (P<0.01). Meanwhile, the increased levels of IL-1 β, IGF-1, TGF-β 1 in serum or myocardial tissue of SHRs, diminished MMP 9 mRNA expression in SHRs were also markedly inhibited after 8 weeks of EA treatment (P<0.05 or P<0.01). Furthermore, the contents of IL-1 β, IGF-1, TGF-β 1 in myocardial tissue were positively correlated with the systolic blood pressure and hydroxyproline respectively (P<0.01).@*CONCLUSION@#EA at bilateral PC 6 could ameliorate cardiac fibrosis in SHRs, which might be mediated by regulation of 1L-1 β/IGF-1-TGF- β 1-MMP9 pathway.

Analysis of cockroach surveillance in Liaoning Province in 2021 / 中国热带医学

@#Abstract: Objective　To master the condition of cockroach population distribution, seasonal dynamics, cockroach density for different habitat, and to provide a basis for developing cockroach control strategies. Methods　Six types of surveillance sites, including residential areas, hotels, restaurants, supermarkets, hospitals and farm product markets, were set up in 14 cities in Liaoning to monitor cockroaches using the sticky-trap method. The cockroach surveillance data from vector surveillance sites in fourteen cities of Liaoning Province in 2021 were collected and statistically analyzed using Excel 2010 and SPSS 23.0 software. The density and species composition of cockroaches were analyzed, and the density difference and seasonal dynamics trend of cockroaches in different habitats were compared. Results　A total of 3 031 cockroaches were captured in 2021, of which Blattella germanica accounted for 94.66% (2 869/3 031) and was the dominant population. The total density of cockroaches was 0.230 0 cockroaches per sheet (3 031/13 234) and the total infestation rate of cockroaches was 5.59% (562/10 052). The density and infestation rate of cockroaches in different habitats were in the order of farm product markets, restaurants, and hotels and the difference in infestation rate between habitats was statistically significant (χ2=168.327, P<0.05). The seasonal dynamics trend of cockroach density and disoperation rate showed a unimodal curve, and the peaks were distributed in July. The seasonal dynamics of cockroach density and disoperation rate in different habitats showed a unimodal curve in the habitats of farm product markets, supermarkets, hotels, hospitals and residential areas all, while the habitats of restaurants were close to a double peak curve. Conclusions　B. germanica is the dominant species of cockroaches in Liaoning Province in 2021. Compared with 2020 the density and disoperation rate of cockroach in 2021 showed a slight downward trend, and the seasonal dynamics trend of cockroach density and disoperation rate showed a unimodal curve. The farm product markets are the key places for cockroach prevention and control. According to the seasonal fluctuation trends in cockroach density and infestation rate in different habitats, comprehensive prevention and control measures should be taken before the peak periods to reduce cockroach density and control diseases.

Cancer health literacy of female breast cancer patients and its influencing factors / 中国实用护理杂志

Objective:To explore the status of cancer health literacy of female patients with breast cancer and analyze its influencing factors, in order to provide a reference for formulating targeted interventions to promote the cancer health literacy of female breast cancer patients.Methods:A cross-sectional survey was conducted. From December 2021 to July 2022, 200 female breast cancer patients hospitalized in Hunan Cancer Hospital were investigated with general information questionnaire, chronic disease patients ′ Health Literacy Management Scale (HeLMS), Strategies Used by People to Promote Health (SUPPH) and Spiritual Attitude and Involvement List (SAIL). Results:The total score of cancer health literacy, self-management self-efficacy and spiritual attitude among female breast patients in this group was 84.63 (75.00, 97.00), 97.30(85.25, 112.00) and 105.00(96.00, 118.00) points. There was a positive correlation between cancer health literacy and self-management efficacy ( r=0.524, P<0.01) and spiritual attitude ( r=0.501, P<0.01). Multiple linear regression analysis showed that education level, average monthly family income, self-management efficacy and spiritual attitude were the influencing factors of cancer health literacy of female breast cancer patients ( t values were 2.86 to 5.91, all P<0.05), which explained 45.7% of the total variation. Conclusions:The cancer health literacy of female patients with breast cancer is at a medium level. Nursing staff can improve the self-management efficacy and spiritual attitude of female patients with breast cancer, so as to improve the level of cancer health literacy and quality of life of patients, and then alleviate the pain of patients.

Tea consumption and cancer: a Mendelian randomization study / 中华流行病学杂志

Objective: A Mendelian randomization (MR) analysis was performed to assess the relationship between tea consumption and cancer. Methods: There were 100 639 participants with the information of gene sequencing of whole genome in the China Kadoorie Biobank. After excluding those with cancer at baseline survey, a total of 100 218 participants were included in this study. The baseline information about tea consumption were analyzed, including daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption. We used the two-stage least square method to evaluate the associations between three tea consumption variables and incidence of cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer. Multivariable MR and analysis only among nondrinkers were used to control the impact of alcohol consumption. Sensitivity analyses were also performed, including inverse variance weighting, weighted median, and MR-Egger. Results: We used 54, 42, and 28 SNPs to construct non-weighted genetic risk scores as instrumental variables for daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption, respectively. During an average of (11.4±3.0) years of follow-up, 6 886 cases of cancer were recorded. After adjusting for age, age2, sex, region, array type, and the first 12 genetic principal components, there were no significant associations of three tea consumption variables with the incidence of cancer and cancer subtypes. Compared with non-daily tea drinkers, the HR (95%CI) of daily tea drinkers for cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer, are respectively 0.99 (0.78-1.26), 1.17 (0.58-2.36), 0.86 (0.40-1.84), 0.85 (0.42-1.73), 1.39 (0.85-2.26) and 0.63 (0.28-1.38). After controlling the impact of alcohol consumption and performing multiple sensitivity analyses, the results were similar. Conclusion: There is no causal relationship between tea consumption and risk of cancer in population in China.

Effects of Munc13-1 and Munc18-1 on dopamine secretion dysfunction in manganese-exposed SH-SY5Y cells / 环境与职业医学

Background Neurotransmitter secretion disorder induced by chronic manganese poisoning has always been one of the important causes of body injury, but the mechanism of neurotransmitter secretion disorder caused by manganese is not clear at present. Objective To investigate the effects of presynaptic membrane intracellular protein 13-1 (Munc13-1) and synapse fusion protein binding protein 18-1 (Munc18-1) on dopamine secretion dysfunction induced by manganese chloride (MnCl2) in human neuroblastoma (SH-SY5Y) cells. Methods A SH-SY5Y cell model induced by MnCl2 was established. Cell viability was measured by MTT assay. Four experimental groups were set up: control group and low-, medium-, and high-dose manganese groups (0, 100, 200, and 400 μmol·L−1 MnCl2). They were treated with corresponding doses of MnCl2 for 24 h. The secretion of dopamine was measured by enzyme-linked immunosorbent assay. The mRNA expression of Syntaxin-1 was detected by real-time quantitaive PCR. Total cell proteins were extracted, and the protein expression levels of Munc13-1, Munc18-1, and Syntaxin-1 were detected by Western blotting. The correlations of MnCl2 exposure and dopamine secretion with the protein expressions of Munc13-1 and Munc18-1 were also analyzed by Pearson correlation. Results Compared with the control group, the cell viability rate decreased gradually with the increase of manganese exposure concentration, and the difference between the medium- and the high-dose manganese groups was statistically significant (P<0.05). The concentration of dopamine in cell culture medium of all manganese exposure groups decreased with the increase of manganese concentration, and compared with the control group and the low-dose manganese group, the medium- and the high-dose manganese groups were statistically significant (P<0.05). The expression of Syntaxin-1 at mRNA or protein level did not change significantly among groups (P>0.05). Compared with the control group, the protein expression of Munc13-1 decreased and that of Munc18-1 increased with the increase of manganese concentration (P<0.05). Compared with the low-dose manganese group, the changes of Munc13-1 protein in the high-dose manganese group and Munc18-1 protein in the medium- and high-dose manganese groups had statistical significance (P<0.05). Compared with the medium-dose manganese group, the protein changes of Munc18-1 in the high-dose manganese group were statistically significant (P<0.05). The correlation analysis showed that MnCl2 dose was negatively correlated with Munc13-1 protein expression (r=−0.898, P<0.05), and positively correlated with Munc18-1 protein expression (r=0.678, P<0.05). Dopamine secretion was positively correlated with Munc13-1 protein expression (r=0.932, P<0.05), and negatively correlated with Munc18-1 protein expression (r=−0.817, P<0.05). Conclusion The inhibition of dopamine secretion in SH-SY5Y cells induced by manganese exposure is related to up-regulation of Munc18-1 and down-regulation of Munc13-1 expression levels, which may be one of the reasons for nerve injury caused by manganese.

Correlation Analysis of Molecularly-Defined Cortical Interneuron Populations with Morpho-Electric Properties in Layer V of Mouse Neocortex / 神经科学通报·英文版

Cortical interneurons can be categorized into distinct populations based on multiple modalities, including molecular signatures and morpho-electrical (M/E) properties. Recently, many transcriptomic signatures based on single-cell RNA-seq have been identified in cortical interneurons. However, whether different interneuron populations defined by transcriptomic signature expressions correspond to distinct M/E subtypes is still unknown. Here, we applied the Patch-PCR approach to simultaneously obtain the M/E properties and messenger RNA (mRNA) expression of >600 interneurons in layer V of the mouse somatosensory cortex (S1). Subsequently, we identified 11 M/E subtypes, 9 neurochemical cell populations (NCs), and 20 transcriptomic cell populations (TCs) in this cortical lamina. Further analysis revealed that cells in many NCs and TCs comprised several M/E types and were difficult to clearly distinguish morpho-electrically. A similar analysis of layer V interneurons of mouse primary visual cortex (V1) and motor cortex (M1) gave results largely comparable to S1. Comparison between S1, V1, and M1 suggested that, compared to V1, S1 interneurons were morpho-electrically more similar to M1. Our study reveals the presence of substantial M/E variations in cortical interneuron populations defined by molecular expression.

Comparison of HPLC fingerprints and determination of main components of Viticis Fructus from different species / 中国中药杂志

In order to comprehensively evaluate the quality of Viticis Fructus, this study established HPLC fingerprints and evaluated the quality of 24 batches of Viticis Fructus samples from different species by similarity evaluation and multivariate statistical analysis(PCA, HCA, PLS-DA). On this basis, an HPLC method was established to compare the content differences of the main components, including casticin, agnuside, homoorientin, and p-hydroxybenzoic acid. The analysis was performed on the chromatographic column(Waters Symmetry C_(18)) with a gradient mobile phase of acetonitrile(A)-0.05% phosphoric acid solution(B) at the flow rate of 1 mL·min~(-1) and detection wavelength of 258 nm. The column temperature was 30 ℃ and the injection volume was 10 μL. The HPLC fingerprint of 24 batches of Viticis Fructus samples was established with 21 common peaks, and nine peaks were identified. Similarity analysis was carried out based on chromatographic data of 24 batches of chromatographic data of Viticis Fructus, and the results showed that except for DYMJ-16, the similarity of Vitex trifolia var. simplicifolia was ≥0.900, while that of V. trifolia was ≤0.864. In addition, the similarity analysis of two different species showed that the similarity of 16 batches of V. trifolia var. simplicifolia was 0.894-0.997 and that of the eight batches of V. trifolia was between 0.990 and 0.997. The results showed that the similarity of fingerprints of these two species was different, but the similarity between the same species was good. The results of the three multivariate statistical analyses were consistent, which could distinguish the two different species. The VIP analysis results of PLS-DA showed that casticin and agnuside contributed the most to the distinction. The content determination results showed that there was no significant difference in the content of homoorientin and p-hydroxybenzoic acid in Viticis Fructus from different species, but the content of casticin and agnuside was significantly different in different species(P<0.01). The content of casticin was higher in V. trifolia var. simplicifolia, while agnuside was higher in V. trifolia. The findings of this study show that there are differences in fingerprint similarity and component content of Viticis Fructus from different species, which can provide references for the in-depth study of the quality and clinical application of Viticis Fructus.

Prokaryotic expression of a recombinant protein of adeno-associated virus capsid conserved regions and preparation of its polyclonal antibody / 南方医科大学学报

OBJECTIVE@#To express and purify the antigenic peptide of adeno-associated virus (AAV) capsid conserved regions in prokaryotic cells and prepare its rabbit polyclonal antibody.@*METHODS@#The DNA sequence encoding the conserved regions of AAV capsid protein was synthesized and cloned into the vector pET30a to obtain the plasmid pET30a-AAV-CR for prokaryotic expression and purification of the conserved peptides. Coomassie blue staining and Western blotting were used to identify the AAV conserved peptides. Japanese big ear white rabbits were immunized with AAV conserved region protein to prepare polyclonal antibody, with the rabbits injected with PBS as the control group. The antibody titer was determined with ELISA, and the performance of the antibody for recognizing capsid protein sequences of AAV1-AAV10 was assessed with Western blotting and immunofluorescence assay.@*RESULTS@#The plasmid pET30a-AAV-CR was successfully constructed, and a recombinant protein with a relative molecular mass of 17000 was obtained. The purified protein induced the production of antibodies against the conserved regions of AAV capsid in rabbits, and the titer of the purified antibodies reached 1:320 000. The antibodies were capable of recognizing a wide range of capsid protein sequences of AAV1-AAV10.@*CONCLUSION@#We successfully obtained the polyclonal antibodies against AAV capsid conserved region protein from rabbits, which facilitate future studies of AAV vector development and the biological functions of AAV.

Wutou Chishizhi Wan Regulates Autophagy and PI3K/Akt/GSK-3β Signaling Pathway in Rats with Myocardial Ischemia-reperfusion Injury / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Wutou Chishizhi Wan in regulating autophagy and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/glycogen synthase kinase-3β （GSK-3β） signaling pathway in rats with myocardial ischemia-reperfusion injury （MIRI）. MethodSixty male SD rats were randomly assigned into the normal group （normal saline）， model group （normal saline）， positive control （trimetazidine， 5.4 mg·kg-1） group， and low-， medium-， and high-dose （1.63， 4.9， 14.7 g·kg-1， respectively） Wutou Chishizhi Wan groups， with 10 rats in each group. The rats in other groups except the normal group underwent left anterior descending coronary artery ligation for modeling. Electrocardiogram was employed to detect the ST-segment elevation to evaluate the modeling. Hematoxylin-eosin （HE） staining was performed to reveal the damage of myocardial tissue. The levels of aspartate aminotransferase （AST） and creatine kinase （CK） were determined by colorimetry， and those of cardiac troponin T （cTnT） and myoglobin （MYO） by enzyme-linked immunosorbent assay （ELISA）. Western blot was carried out to determine the protein levels of microtubule-associated proteins 1 light chain 3 （LC3）， autophagy-related gene Beclin-1， PI3K， Akt， GSK-3β， p-GSK-3β， and p-Akt. ResultCompared with the normal group， the modeling elevated the serum levels of AST， CK， cTnT， and MYO （P<0.01）， destroyed the arrangement of myocardial cells abd nucle， twisted and broken myocardial fibers， up-regulated the protein levels of LC3Ⅱ/Ⅰ and Beclin-1 （P<0.01）， and down-regulated the protein levels of PI3K， p-Akt， and p-GSK-3β （P<0.01）. Compared with the model group， trimetazidine and Wutou Chishizhi Wan （all the doses） lowered the levels of AST， CK， cTnT， and MYO in serum （P<0.01）， restored the arrangement of myocardial cells and muscle fibers， reduced necrosis， down-regulated the protein level of Beclin-1 （P<0.01）， and up-regulated the protein levels of PI3K， p-Akt， and p-GSK-3β （P<0.01）. Additionally， Wutou Chishizhi Wan （all the doses） down-regulated the protein level of LC3Ⅱ/Ⅰ （P<0.05， P<0.01）. Compared with those in the trimetazidine group， the serum AST level rose in the low-dose Wutou Chishizhi Wan group （P<0.05） and declined in the high-dose group （P<0.01）， and the protein level of Beclin-1 was down-regulated in the medium-dose group （P<0.01）. Additionally， the trimetazidine group had higher protein level of LC3Ⅱ/Ⅰ than medium- and high-dose Wutou Chishizhi Wan groups （P<0.05， P<0.01）， higher protein level of PI3K than low-， medium-， and high-dose groups （P<0.01）， lower protein level of p-Akt than low- and medium-dose groups （P<0.01）， and higher p-GSK-3β protein level than the medium-dose group （P<0.01）. ConclusionDifferent doses of Wutou Chishizhi Wan can ameliorate MIRI， and the high dose has the best effect. Wutou Chishizhi Wan can reduce the activity of myocardial injury markers AST， CK， cTnT， and MYO， and alleviate the pathological damage of myocardial tissue. It can down-regulate the protein levels of beclin-1， LC3Ⅱ/Ⅰ， and up-regulate those of PI3K， p-Akt， and p-GSK-3β. In summary， Wutou Chishizhi Wan may inhibit excessive autophagy and regulate the PI3K/Akt/GSK-3β signaling pathway to exert protective effect on MIRI rats.

Clinical observation of chiropractic manipulation in the treatment of degenerative scoliosis / 中国骨伤

OBJECTIVE@#To observe clinical efficacy of chiropractic manipulation in the treatment of degenerative scoliosis (DS).@*METHODS@#From June 2017 to September 2019, 120 patients with degenerative scoliosis were randomly divided into treatment group (60 cases) and control group(60 cases). The patients in treatment group were treated with chiropractic manipulation once every other day for 4 weeks. The patients in control group were treated with eperisone hydrochloride tablets combined with thoracolumbar orthopedic(TSLO)brace, oral eperisone hydrochloride tablets 50 mg three times a day, wearing TSLO brace for not less than 8 hours a day. The course of treatment was 4 weeks. After the patients were selected into the group, visual analogue scale (VAS) and Oswestry Disability Index (ODI) were recorded before treatment, 1, 2, 3, 4 weeks after treatment and 1 month after treatment. The full length X-ray of the spine was taken before and 4 weeks after treatment, and the scoliosis Cobb angle, sagittal vertical axis (SVA) and lumbar lordosis (LL) were measured and compared. The adverse reactions during the treatment were recorded.@*RESULTS@#There were significant differences in VAS and ODI between two groups at each time point after treatment (P<0.001), VAS and ODI at 2 weeks after treatment (PVAS=0.025, PODI=0.032) and 3 weeks after treatment(PVAS=0.040, PODI=0.044) in treatment group were significantly different from those in control group, but there was no significant difference in VAS and ODI at other time points between treatment group and control group (P>0.05). There was significant difference in Cobb angle between treatment group(P=0.010) and control group(P=0.017) after treatment, but there was no significant difference in LL and SVA between treatment group and control group. There was no significant difference in Cobb angle, LL and SVA between two groups before and after treatment. During the treatment, there were 4 mild adverse reactions in the control group and no adverse reactions in the treatment group.@*CONCLUSION@#Chiropractic manipulation can effectively relieve pain and improve lumbar function in patients with degenerative scoliosis. The onset of action is faster than that oral eperisone hydrochloride tablets combined with TSLO brace, and it has better safety and can improve Cobb angle of patients with degenerative scoliosis.

Construction and anti-tumor efficiency evaluation of redox-responsive micelles for the co-delivery of IR-780 and 18β-glycyrrhetinic acid / 药学学报

Photothermal therapy (PTT) is a highly effective anti-tumor method. However, when laser radiation was used to ablate tumors, it usually triggers a series of inflammatory reactions, promoting the further development of tumors and affecting the effect of anti-tumor therapy. Therefore, it is an effective method to improve the anti-tumor effect by suppressing the inflammatory response through the precise targeted delivery of anti-inflammatory drug while realizing the photothermal treatment of tumors. To this end, the redox-responsive linker 3,3'-dithiodipropionic acid was used to bond the classic hydrophobic anti-inflammatory drug 18β-glycyrrhetinic acid (18β-GA) and the hydrophilic fragment methoxy-polyethylene glycol (mPEG-NH2) to obtain redox-responsive amphiphilic polymer PEG-DA-GA in this study. Then, photothermal agent IR-780 was encapsulated to prepare redox-responsive polymer micelle PDG/IR-780 NPs. The PDG/IR-780 NPs exhibited uniform particle size of 80.2 ± 5.3 nm and the polydispersity index (PDI) was 0.215 ± 0.079. All animal experiments followed the ethical requirements formulated by the Ethics Committee of Sichuan University. The results showed that PDG/IR-780 NPs could respond to the abundant glutathione (GSH) in tumor cells to promote the disintegration of nanoparticle and the release of 18β-GA, thus significantly improved the killing efficiency on 4T1 cells, when compared with the non-redox-responsive control PSG/IR-780 NPs. When the concentration of 18β-GA was 50 μg·mL-1, the cell viability of 4T1 cells in the PDG/IR-780 NPs group was only (19.29 ± 1.80) %, which was significantly lower than the result of in PSG/IR-780 NPs group (29.30 ± 1.37) %. The results of frozen sections of tumor tissues showed that the designed PDG NPs can promote the tumor-targeted distribution of drugs compared with the free drug group. Eventually, PDG/IR-780 NPs achieved wonderful anti-tumor efficacy on 4T1 triple-negative breast cancer model, revealing the new possibility of the combined therapy strategy of photothermal and anti-inflammatory therapy.

Mechanism of Biejiajian Wan Against EMT of Hepatocellular Carcinoma Cells Through NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Biejiajian Wan （BJJW） on transforming growth factor-β1 （TGF-β1）-induced epithelial-mesenchymal transition （EMT） of HepG2 cells， and explore its mechanism against EMT of hepatocellular carcinoma cells. MethodHepG2 cells were randomly divided into a blank group， a TGF-β1 model group （10 μg·L-1 TGF-β1）， a low-dose BJJW group （10 μg·L-1 TGF-β1+0.55 g·kg-1 BJJW）， a medium-dose BJJW group （10 μg·L-1 TGF-β1+1.1 g·kg-1 BJJW）， a high-dose BJJW group （10 μg·L-1 TGF-β1+2.2 g·kg-1 BJJW）， and a sorafenib group （10 μg·L-1 TGF-β1+0.03 g·kg-1 sorafenib）. The EMT model was induced by 10 μg·L-1 TGF-β1 in HepG2 cells. After treatment with corresponding medicated serum， cell counting kit -8 （CCK-8） assay was used to detect cell proliferation. Cell migration ability was detected by the Transwell assay and wound healing assay. The protein expression related to EMT and nuclear factor-kappa B （NF-κB） signaling pathway was detected by cell immunofluorescence assay and Western blot. ResultCompared with the blank group 4 days later， the TGF-β1 model group showed fusiform and loose cells with widened gap and antennae reaching out， decreased protein expression of E-cadherin （P<0.05）， and increased protein expression of N-cadherin and vimentin （P<0.05）， which indicated that the EMT model was properly induced in HepG2 cells by TGF-β1 stimulation for 4 days. After 48 hours of treatment with the corresponding medicated serum， each medication group showed inhibited proliferation of HepG2 cells that had undergone EMT， especially the low- and high-dose BJJW groups （P<0.01）， and the medium-dose BJJW group showed increased E-cadherin protein expression （P<0.05） and decreased p-p65， N-cadherin， and vimentin protein expression （P<0.05）， as compared with the TGF-β1 model group. As revealed by the transwell assay and wound healing assay， TGF-β1 enhanced the migration ability of HepG2 cells （P<0.05， P<0.01） compared with the results in the blank group， compared with the TGF-β1 model group， the medication groups showed inhibited migration ability of HepG2 cells （P<0.05， P<0.01）. Compared with the blank group， the TGF-β1 model group promoted the expression of p65 and Snail into the nucleus. Compared with the TGF-β1 model group， the medication groups inhibited the expression of p65 and Snail into the nucleus. ConclusionBJJW may inhibit the EMT， proliferation， and migration of HepG2 cells induced by TGF-β1 by suppressing the NF-κB signaling pathway to exert an anti-hepatocellular carcinoma effect.

Observation and study on uncorrected distance visual acuity and ocular adjustment function before and after excimer laser photorefractive keratectomy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the changes of uncorrected distance visual acuity(UCDVA)and ocular accommodation before and after excimer laser photorefractive keratectomy(PRK).METHODS: A retrospective study. There were 120 patients(240 eyes)who underwent PRK surgery in our center from December 2017 to December 2019 divided into two groups according to the diopter of spherical equivalent(SE): 70 cases with SE≤-6.00D in the mild to moderate myopia group and 50 cases with -6.00D&#x003C;SE≤-9.00D in the high myopia group which were observed and analyzed. The UCDVA(LogMAR), monocular accommodative amplitude(AMP), negative relative accommodation(NRA), positive relative accommodation(PRA)and monocular accommodative flipper(AF)were measured before and after operation at 1wk, 1 and 3mo. RESULTS: In the group of low-moderate myopia and high-myopia group, the UCDVA at 1wk, 1 and 3 mo after operation was significantly increased compared with those before operation(all P&#x003C;0.01). The increase of UCDVA of low to moderate myopia group was better than that in the high myopia group at 3mo after operation(P&#x003C;0.05). Monocular AMP in the both groups firstly decreased and increased afterwards, and there was a significant decrease than that before operation at 1wk and 1mo after operation(P&#x003C;0.01). AMP reached and was better than that before operation at 3mo after operation(P&#x003C;0.01). The increase of low to moderate myopia group was both higher and faster than that of high myopia group. Compared with PRA before operation, the patients of low to moderate myopia group decreased at 1wk after operation(P&#x003C;0.01), postoperative levels at 1mo recovered to preoperative level(P&#x003E;0.05)and postoperative at 3mo was superior to preoperative operation(P&#x003C;0.05); High myopia group did not change significantly at 1wk and 1mo after operation compared with preoperative operation(P&#x003E;0.05), and increased at 3mo after operation compared with preoperative level(P&#x003C;0.01). For low to moderate myopia group, there was no significant difference in preoperative and postoperative NRA, and at 1wk after operation, NRA of high myopia group temporarily increased compared with preoperative operation(P&#x003C;0.01). At 1mo after operation, it returned to the preoperative level(P&#x003E;0.05), and significantly increased at 3mo after operation compared with preoperative operation(P&#x003C;0.01). Monocular AF for both groups significantly decreased at 1wk after operation compared with preoperative operation, recovered at 1mo after operation and was significantly better at 3mo after operation(all P&#x003C;0.01); The low-to-moderate group increased more than the high-myopia group.CONCLUSION: PRK has a good correction effect for myopia below -9.00D, and people in low to moderate myopia have a better postoperative UCDVA correction effect than those in high myopia. The eye accommodation will be abnormal in a short period after operation. The recovery and improvement time of accommodative function in low-moderate myopia group are shorter than that in high myopia group, but both groups can recover and improve at 3mo after operation compared with the preoperative levels.

Clinical efficacy of combined therapy in children with stage 4 neuroblastoma / 中国当代儿科杂志

OBJECTIVES@#To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma.@*METHODS@#A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021.@*RESULTS@#The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years.@*CONCLUSIONS@#Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.

Involvement of ET-1/eNOS in the ameliorating effect of electroacupuncture on cardiac dysfunction in rats with spontaneously hypertensive / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on cardiac function of ventriculus sinister in rats with spontaneously hypertensive (SHR), and to explore the mediation effect of endothelin-1 (ET-1)/endothelial nitric oxide synthase (eNOS).@*METHODS@#Six 12-week-old male Wistar Kyoto (WKY) rats were taken as the normal group. Eighteen 12-week-old SHR were randomly divided into a model group, an EA group and a sham EA group, 6 rats in each group. The rats in the EA group were treated with EA (disperse-dense wave, 2 Hz/15 Hz in frequency, 1 mA in current intensity) at "Neiguan" (PC 6), 30 min each time, once a day for 8 weeks. The rats in the sham EA group were treated with superficial needling at "Neiguan" (PC 6) with no electrical stimulation applied. After treatment, the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were tested by echocardiographic analysis. The left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), heart rate (HR), the maximum rate of increase/decrease of left ventricular pressure (±dp/dtmax) were detected. The serum content of ET-1 was detected by ELISA. Western blot was used to evaluate the expression of ETAR, eNOS in myocardial tissue of left ventricular.@*RESULTS@#Compared with the normal group, LVEF, LVFS, +dp/dtmax/LVSP and -dp/dtmax/LVSP were decreased (P<0.01, P<0.05), while LVSP, LVEDP, +dp/dtmax and -dp/dtmax were increased (P<0.01) in the model group. Compared with the model group, LVEF, LVFS, +dp/dtmax/LVSP and -dp/dtmax/LVSP were increased (P<0.01, P<0.05), and LVSP and LVEDP were decreased (P<0.01) in the EA group. Compared with the normal group, the serum content of ET-1 and the expression of ETAR in myocardial tissue were increased (P<0.01), whereas expression of eNOS was decreased (P<0.01) in the model group. Compared with the model group, the serum content of ET-1 and the expression of ETAR in myocardial tissue were decreased (P<0.05), whereas expression of eNOS was increased (P<0.05) in the EA group.@*CONCLUSION@#EA intervention may alleviate hypertensive cardiac function damage by up-regulating the expression of eNOS protein in myocardial tissue, down-regulating the serum content of ET-1 and the expression of ETAR protein in myocardial tissue.

Progress on the pathogenesis and treatment of IgG4-related disease / 药学学报

IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition of autoimmune etiology in recent twenty years, mainly manifesting as mass-forming lesions in single or multiple organs. In the past, it was often missed or misdiagnosed as inflammation or tumor. Patients may die from multiple organ failure due to end-stage fibrosis if they are not treated promptly. However, the number of clinically confirmed cases has gradually increased with the improvement of diagnostic level in recent years, and these patients have benefited greatly after receiving early treatment. Although patients generally respond well to traditional immunosuppressors including glucocorticoids and disease-modifying anti-rheumatic drugs, refractory and recurrent cases, even patients with glucocorticoid contraindication are common. Important mechanistic insights have been derived from studies of B-cell depletion therapy, but greater awareness of the pathophysiology of IgG4-RD is still badly needed to identify novel therapeutic targets. In this article, we reviewed the pathogenesis progress and promising therapy of IgG4-RD to seek better clinical management of IgG4-RD.

Analysis of efficacy and safety of patients after LASIK surgery in 20 years / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate long-term efficacy and safety of patients after excimer laser in situ keratomileusis(LASIK)surgery in 20a.METHODS: A retrospective study.Patients who underwent LASIK in our hospital from January 1998 to December 2001 were recruited. The patients were notified by telephone to the outpatient for follow-up. The collected data included demographic characteristics(gender and age), preoperative uncorrected distance visual acuity(UCVA)and best corrected visual acuity(BCVA), preoperative diopter, intraoperative corneal flap thickness and corneal stromal residual thickness(RST). The main indicators were long-term efficacy index, safety index, UCVA, BCVA, corneal thickness and axial length. The slit lamp, fundus and optical coherence tomography(OCT)examination were performed at the same time.RESULTS: A total of 95 patients(190 eyes)were recruited. At the final postoperative visit, there were 71 patients(142 eyes, 74.7%)had UCVA≥1.0, and 82 patients(164 eyes, 86.3%)had BCVA≥1.0. There were 2 eyes among them had bad BCVA(≤0.6)due to macular retinoschisis and glaucoma, respectively, while other patients' BCVA was 0.8. There was no significant correlation between the UCVA and BCVA of patients after surgery in 20a and the factors such as age at surgery, preoperative diopter and corneal thickness(P&#x003E;0.05), but there was a negative correlation with the increase of axis length(rs=-0.32, -0.31, all P&#x003C;0.05). UCVA and BCVA were positively correlated with corneal stromal residual thickness at the last postoperative follow-up(P&#x003C;0.05). The safety and efficacy indexes of LASIK after surgery in 20a were 1.00±0.10 and 0.83±0.27, respectively. During the follow-up, no patients were found to have corneal ectasia and complications related to corneal flap, and no patients underwent secondary surgery. No patients with corneal dryness were found after silt lamp examination.CONCLUSION: LASIK after surgery in 20a shows good safety and efficacy.