N-Benzyl matrinol was obtained by hydrolysis, benzylation and reduction reaction from matrine. A series of hybrids (8a-8n) from (phenylsulfonyl)furoxan and N-benzyl matrinol were synthesized and biologically evaluated as anti-hepatocellular carcinoma agents. All target compounds were evaluated for anti-proliferative activity against human hepatocellular Bel-7402, SMMC-7721, Bel-7404, and HepG2 cells in vitro by MTT method. The results indicated that all of these compounds had potent anti-proliferative activity which were more potent than their parent compound and 5-FU, especially 8a-8h and 8j showed the strongest anti-HCC HepG2 cell activity with IC50 values of 0.12-0.93 μmol x L(-1).

Objective To summary the therapy outcome of retroperitoneal laparoscopic treatment on upper ureteral calculi.Methods The retroperitoneal laparoscopic treatment were performed to all cases from Jun.2011 to Jun.2012 in our hospital.All cases were treated with 3-hold method (two 10 mm and one 5 mm ports).The retroperitoneal space was made by a combination of blunt and balloon dissection,and the space was maintained with CO2 Ureteral longitudinal incision was made to remove the stones,and double J catheter was served as stent drainage.Absorbable suture was used to suture ureteral incision.Results A retroperitoneal approach was performed in 12 patients,and another patient was conducted the open surgery because the stone cower in the kidney calices.Operative periods ranged from 55 to 132 min (average was 85 min).There were no significant postoperative complications.Conclusion It is a minimally invasive and effective approach in the therapy of upper urerteral calculi with laparoscopic.

Objective:To summarize the application rules of acupuncture and moxibustion in the clinical trials for dysmenorrhea and endometriosis.Methods:The relevant articles of clinical research on acupuncture and moxibustion for the treatment of dysmenorrhea in endometriosis were retrieved electronically from CNKI, Wanfang, VIP, PubMed and Cochrane Library (Retrieved from database establishment until 31 October 2021). The clinical literatures that met the inclusion criteria were included into the database (Microsoft Office Excel 2019), and the main table and sub-table were established through Microsoft Office Excel 2019. Descriptive statistic analysis was performed by using SPSS 26.0 software. StataSE15 (64-bit) software was used to analyze the correlation between the combinations of acupoints with single acupoint frequency>5.Results:A total of 40 clinical studies were included. Of them, the top 3 acupuncture methods according to the frequency were acupuncture (11 times), moxibustion (11 times), and electro-acupuncture (8 times), the top 3 acupuncture points used according to the frequency were Guan Yuan (34 times), San Yin Jiao (26 times), and Zhong Ji (25 times), the top 3 meridians of the body acupuncture points according to the frequency were Ren Meridian (36 times), Spleen Meridian (32 times), and Stomach Meridian (22 times). According to the correlation analysis, body points of Guan Yuan, San Yin Jiao, Uterus, Qi Hai and Zhong Ji were stronge related.Conclusion:Acupuncture can effectively treat EMT dysmenorrhea with less adverse reactions. The methods are mainly acupuncture, moxibustion and electroacupuncture, mostly local acupoints, intersection acupoints and empirical acupoints.

The purpose of this investigation was to develop Pluronic F-127 coated N-trimethyl chitosan nanoparticles(F-S NPs)of insulin as the model drug and asses their penetration of the mucosal barriers. Single factor screening was used to optimize the formulations of nanoparticles and the nanoparticles were characterized. Their particle size, Zeta potential, encapsulation efficiencies and drug loading were assayed to be(240. 6±6. 51)nm, (10. 42±1. 60)mV, (43. 39±2. 83)% and(3. 39±0. 57)%, respectively. The impact of PF-127 on mucin binding in vitro and nanoparticles′s transport in freshly obtained mucus were also evaluated. The mucin affinity of F-S NPs was significantly reduced when compared to that of the N-trimethyl chitosan nanoparticles(S NPs), i. e. , 28% of the latter. And F-S NPs was found to have an improved mucosal penetrating capability. Mucus-secreting HT29-MTX-E12(E12)cell monolayer was selected to investigate their cellular uptake. F-S NPs exhibited higher penetration coefficient than both free insulin and S NPs in mucus-secreting epithelium cells, i. e. , 16-fold and 1. 4-fold, respectively. Data suggest that F-S NPs be potential carriers to cross mucosal barriers and enhance the cellular uptake of insulin.

Objective To investigate the effects of aluminum lactate exposure on learning and memory and the transportation of amyloid-beta peptides (Aβ) in cerebrospinal fluid in rats.Methods A total of 80 male Sprague-Dawley rats were randomly divided into solvent control (distilled water) group and low-,medium-,and high-dose aluminum poisoning groups (10,30,and 90 mg/kg aluminum lactate),with 20 rats in each group,and the poisoning procedure was performed by gavage for 2 months.The Morris water maze test was used to test the rats' learning and memory,Western blot was used to measure the expression level of low-density lipoprotein receptor protein-1 (LRP-1) in rats' choroid plexus,and enzyme-linked immunosorbent assay (ELISA) was used to measure the content of Aβ in the cerebrospinal fluid and plasma.Results The Morris water maze test showed that in the place navigation test,with the increasing training time,the escape latency was significantly shortened in each group and showed significant differences between any two groups (P＜0.05).In the spatial probe test,the time spent in target quadrant in the medium-and high-dose groups was 11.52±1.56 s and 10.43 ±5.27 s,respectively,which was significantly shorter than that in the control group and the low-dose group (15.81±3.01 s and 13.91±2.17 s)(P＜0.05).The numbers of platform crossings in the medium-and high-dose groups were 2.64± 1.39 and 1.50±0.76,respectively,which were significantly lower than those in the control group and the low-dose group (4.29±0.914 and 3.56±1.38)(P＜0.05).The results of ELISA showed that the medium-and high-dose groups had significant increases in the content of Aβ1-42 in cerebrospinal fluid (320.35±84.82 pg/ml and 327.68±67.51 pg/ml),which was significantlyhigher than that in the control group(203.46±74.36 pg/ml) (P＜0.05).The content of Aβ1-42 in plasma showed no significant difference between any two groups (P＞0.05),and that of Aβ1-40 in cerebrospinal fluid and plasma also showed no significant difference between any two groups (P＞0.05).The results of Western blot showed that the high-dose group had significantly lower protein expression of LRP-1 than the control group and the low-and medium-dose groups(0.57±0.21 vs 1.00±0.00/0.79±0.15/0.95±0.24,P＜0.05).Conclusion Subchronic aluminum exposure may reduce learning and memory in rats,and the accumulation of Aβ in cerebrospinal fluid may be related to the reduced protein expression of LRP-1 in the choroid plexus,suggesting that aluminum affects learning and memory in rats through reducing the protein expression of LRP-1,influencing the transportation of Aβ,and leading to the accumulation of Aβ.

Objective To investigate the impairment in primary cultured rat choroid plexus epithelial cells (CPECs) induced by aluminum.Methods The choroid plexus isolated from Sprague-Dawley rats 14 days old was cut into pieces and digested by trypsin in the sterile area.The obtained single cells were cultured in DMEM with 1％ epidermal growth factor and 20％ fetal calf serum.Five days later,immunohistochemistry with anti-transthyretin antibody was used to identify the purity of cultured cells.The well-grown cells were treated with aluminum lactate at different concentrations (0,100,400,and 1 600 μmol/L for control,low-dose,medium-dose,and high-dose groups).Forty-eight hours later,the cell viability,apoptotic rate,level of reactive oxygen species (ROS),and activity of superoxide dismutase (SOD) were measured in each group to evaluate the impairment in primary cultured rat CPECs by aluminum.Results More than 95％ of the cultured cells were identified as CPECs.The medium-and high-dose groups had significantly lower cell viability than the control group (86.74％±4.03％ vs 100％,P＜0.01;81.90％±9.17％ vs 100％,P＜0.01).The high-dose group had significantly lower cell viability than the low-dose group (81.90％±9.17％ vs 92.92％±8.81％,P＜0.01).The medium-and high-dose groups had significantly higher apoptotic rates than the control group (7.26％±0.99％ vs 1.29％±0.03％,P＜0.01;22.25％±1.55％ vs 1.29％±0.03％,P＜0.01) and the low-dose group (7.26％±0.99％ vs 1.68％±0.27％,P＜0.01;22.25％±1.55％ vs 1.68％±0.27％,P＜0.01).The high-dose group had a significantly higher apoptotic rate than the medium-dose group(22.25％±1.55％ vs 7.26％±0.99％,P＜0.01).The medium-and high-dose groups had significantly higher fluorescence intensity of ROS than the control group (22.23％±0.41％ vs 17.24％±0.09％,P＜0.05;25.10％±1.13％ vs 17.24％±0.09％,P＜0.05) and the low-dose group (22.23％± 0.41％ vs 18.31％±0.21％,P＜0.05;25.10％±1.13％ vs 18.31％±0.21％,P＜0.05).The high-dose group had significantly higher fluorescence intensity of ROS than the medium-dose group (25.10％±1.13％ vs 22.23％± 0.41％,P＜0.05).The low-,medium-and high-dose groups had significantly lower SOD activity than the control group[(28.65±0.74) U/g Hb vs (37.35±1.05) U/g Hb,P＜0.05;(22.75±1.94) U/g Hb vs (37.35±1.05) U/g Hb,P＜0.05;(13.29 ±0.64) U/g Hb vs (37.35 ± 1.05) U/g Hb,P＜0.05].The medium-and high-dose groups had significantly lower SOD activity than the low-dose group [(22.75±1.94) U/g Hb vs (28.65±0.74) U/g Hb,P＜ 0.05;(13.29±0.64) U/g Hb vs (28.65±0.74) U/g Hb,P＜0.05],while the high-dose group had had significantly lower SOD activity than the medium-dose group[(13.29±0.64) U/g Hb vs (22.75±1.94) U/g Hb,P＜0.05].There were no significant differences in cell viability,apoptotic rate,level of ROS,or activity of SOD between any other two groups (P＞0.05).Conclusion Aluminum lactate may induce impairment in primary cultured rat CPECs.It reduces the cell viability,elevates the apoptotic rate,and causes oxidative stress.

Objective To investigate the effects of aluminum lactate exposure on learning and memory and the transportation of amyloid-beta peptides (Aβ) in cerebrospinal fluid in rats.Methods A total of 80 male Sprague-Dawley rats were randomly divided into solvent control (distilled water) group and low-,medium-,and high-dose aluminum poisoning groups (10,30,and 90 mg/kg aluminum lactate),with 20 rats in each group,and the poisoning procedure was performed by gavage for 2 months.The Morris water maze test was used to test the rats' learning and memory,Western blot was used to measure the expression level of low-density lipoprotein receptor protein-1 (LRP-1) in rats' choroid plexus,and enzyme-linked immunosorbent assay (ELISA) was used to measure the content of Aβ in the cerebrospinal fluid and plasma.Results The Morris water maze test showed that in the place navigation test,with the increasing training time,the escape latency was significantly shortened in each group and showed significant differences between any two groups (P＜0.05).In the spatial probe test,the time spent in target quadrant in the medium-and high-dose groups was 11.52±1.56 s and 10.43 ±5.27 s,respectively,which was significantly shorter than that in the control group and the low-dose group (15.81±3.01 s and 13.91±2.17 s)(P＜0.05).The numbers of platform crossings in the medium-and high-dose groups were 2.64± 1.39 and 1.50±0.76,respectively,which were significantly lower than those in the control group and the low-dose group (4.29±0.914 and 3.56±1.38)(P＜0.05).The results of ELISA showed that the medium-and high-dose groups had significant increases in the content of Aβ1-42 in cerebrospinal fluid (320.35±84.82 pg/ml and 327.68±67.51 pg/ml),which was significantlyhigher than that in the control group(203.46±74.36 pg/ml) (P＜0.05).The content of Aβ1-42 in plasma showed no significant difference between any two groups (P＞0.05),and that of Aβ1-40 in cerebrospinal fluid and plasma also showed no significant difference between any two groups (P＞0.05).The results of Western blot showed that the high-dose group had significantly lower protein expression of LRP-1 than the control group and the low-and medium-dose groups(0.57±0.21 vs 1.00±0.00/0.79±0.15/0.95±0.24,P＜0.05).Conclusion Subchronic aluminum exposure may reduce learning and memory in rats,and the accumulation of Aβ in cerebrospinal fluid may be related to the reduced protein expression of LRP-1 in the choroid plexus,suggesting that aluminum affects learning and memory in rats through reducing the protein expression of LRP-1,influencing the transportation of Aβ,and leading to the accumulation of Aβ.

Objective To investigate the impairment in primary cultured rat choroid plexus epithelial cells (CPECs) induced by aluminum.Methods The choroid plexus isolated from Sprague-Dawley rats 14 days old was cut into pieces and digested by trypsin in the sterile area.The obtained single cells were cultured in DMEM with 1％ epidermal growth factor and 20％ fetal calf serum.Five days later,immunohistochemistry with anti-transthyretin antibody was used to identify the purity of cultured cells.The well-grown cells were treated with aluminum lactate at different concentrations (0,100,400,and 1 600 μmol/L for control,low-dose,medium-dose,and high-dose groups).Forty-eight hours later,the cell viability,apoptotic rate,level of reactive oxygen species (ROS),and activity of superoxide dismutase (SOD) were measured in each group to evaluate the impairment in primary cultured rat CPECs by aluminum.Results More than 95％ of the cultured cells were identified as CPECs.The medium-and high-dose groups had significantly lower cell viability than the control group (86.74％±4.03％ vs 100％,P＜0.01;81.90％±9.17％ vs 100％,P＜0.01).The high-dose group had significantly lower cell viability than the low-dose group (81.90％±9.17％ vs 92.92％±8.81％,P＜0.01).The medium-and high-dose groups had significantly higher apoptotic rates than the control group (7.26％±0.99％ vs 1.29％±0.03％,P＜0.01;22.25％±1.55％ vs 1.29％±0.03％,P＜0.01) and the low-dose group (7.26％±0.99％ vs 1.68％±0.27％,P＜0.01;22.25％±1.55％ vs 1.68％±0.27％,P＜0.01).The high-dose group had a significantly higher apoptotic rate than the medium-dose group(22.25％±1.55％ vs 7.26％±0.99％,P＜0.01).The medium-and high-dose groups had significantly higher fluorescence intensity of ROS than the control group (22.23％±0.41％ vs 17.24％±0.09％,P＜0.05;25.10％±1.13％ vs 17.24％±0.09％,P＜0.05) and the low-dose group (22.23％± 0.41％ vs 18.31％±0.21％,P＜0.05;25.10％±1.13％ vs 18.31％±0.21％,P＜0.05).The high-dose group had significantly higher fluorescence intensity of ROS than the medium-dose group (25.10％±1.13％ vs 22.23％± 0.41％,P＜0.05).The low-,medium-and high-dose groups had significantly lower SOD activity than the control group[(28.65±0.74) U/g Hb vs (37.35±1.05) U/g Hb,P＜0.05;(22.75±1.94) U/g Hb vs (37.35±1.05) U/g Hb,P＜0.05;(13.29 ±0.64) U/g Hb vs (37.35 ± 1.05) U/g Hb,P＜0.05].The medium-and high-dose groups had significantly lower SOD activity than the low-dose group [(22.75±1.94) U/g Hb vs (28.65±0.74) U/g Hb,P＜ 0.05;(13.29±0.64) U/g Hb vs (28.65±0.74) U/g Hb,P＜0.05],while the high-dose group had had significantly lower SOD activity than the medium-dose group[(13.29±0.64) U/g Hb vs (22.75±1.94) U/g Hb,P＜0.05].There were no significant differences in cell viability,apoptotic rate,level of ROS,or activity of SOD between any other two groups (P＞0.05).Conclusion Aluminum lactate may induce impairment in primary cultured rat CPECs.It reduces the cell viability,elevates the apoptotic rate,and causes oxidative stress.

Objective:To explore the clinical and genetic characteristics of two children with a clinical diagnosis of Treacher Collins syndrome (TCS).Methods:Whole-exome sequencing was used to screen potential variants in the two children. Confirmation of suspected variants was performed through Sanger sequencing , multiplex ligation dependent probe amplification and real-time PCR in probands and their parents.Results:A heterozygous deletion variant, c. 4357_4360delGAAA, was detected in case one, while was de novo and verified by Sanger sequencing. Thevariant was classified as pathogenic(PVS1 + PM2+ PM6)according to ACMG guideline. The heterozygous deletion of exon 1-7 was seen in the same gene in case 2, which MLPA verified as heterozygous deletion of exon 1-6. This deletion was inherited from the father with a normal phenotype, and the father’s TCOF1 gene was suspected to be chimeric heterozygous deletion of exon 1-6 verified by MLPA. Conclusion:The identified variants in the TCOF1 gene probably underlie the two cases of TCS. There was no apparent correlation between genotype and phenotype. In addition, it shows a high interfamilial variability ranging from normal to full presentation of TCS. Genetic detection provided clinical diagnosis and genetic counselling for TCS patients .

Objective:To analyze the genetic mutations and clinical features of the subtypes of classical BCR-ABL-negative myeloproliferative neoplasm (MPN) .Methods:Mutations of 108 newly diagnosed BCR-ABL-negative MPN patients [including 55 patients with essential thrombocytopenia (ET) , 24 with polycythemia vera (PV) , and 29 with primary myelofibrosis (PMF) ] were identified using next-generation sequencing with 127-gene panel, and the relationship between gene mutations and clinical features were analyzed.Results:Total 211 mutations in 32 genes were detected in 100 MPN patients (92.59% ) , per capita carried (1.96±1.32) mutations. 85.19% (92/108) patients carried the driver gene (JAK2, CALR, MPL) mutations, 69.56% (64/92) of these patients carried at least 1 additional gene mutation. In descending order of mutation frequency, the highest frequency was for activation signaling pathway genes (42.2% , 89/211) , methylation genes (17.6% , 36/211) , and chromatin-modified genes (16.1% , 34/211) . There was a significant difference in the number of mutations in the activation signaling pathway genes, epigenetic regulatory genes, spliceosomes, and RNA metabolism genes among the three MPN subgroups. The average number of additional mutations in PMF patients was higher than that in ET and PV patients (1.69±1.39, 0.67±0.70, 0.87±1.22, χ2=13.445, P=0.001) . MPN-SAF-TSS (MPN 10 score) ( P=0.006) and myelofibrosis level ( P=0.015) in patients with ≥ 3 mutant genes were higher and the HGB level ( P=0.002) was lower than in those with<3 mutations. Twenty-six patients (24.1% ) carried high-risk mutation (HMR) , and patients with HMR had lower PLT ( P=0.017) , HGB levels ( P<0.001) , and higher myelofibrosis level ( P=0.010) and MPN10 score ( P<0.001) . The frequency of ASXL1 mutations was higher in PMF than in PV patients (34.5% vs. 4.2% , P=0.005) . PMF patients with ASXL1 had lower levels of PLT and HGB ( P=0.029 and 0.019) . Conclusion:69.56% of MPN patients carry at least one additional mutation, and 24.1% patients had HMR. Each subgroup had different mutation patterns. PMF patients had a higher average number of additional gene mutations, especially a higher frequency of ASXL1 mutation; PLT and HGB levels were lower in ASXL1 mutation PMF patients.