In recent years, cancer treatment methods and means are becoming more and more diversified, and single treatment methods often have limited efficacy, while the synergistic effect of immunity combined with chemotherapy can inhibit tumor growth more effectively. Based on this, we constructed a sodium alginate hydrogel composite system loaded with chemotherapeutic agents and tumor vaccines (named SA-DOX-NA) with a view to the combined use of chemotherapeutic agents and tumor vaccines. Firstly, the tumor vaccine (named NA) degradable under acidic conditions was constructed by in situ polymerization using chicken ovalbumin (OVA), acrylamide (AAM) and 2-(dimethylamino) ethyl methacrylate (DMAEMA) monomer. Then a hydrogel composite system SA-DOX-NA co-loaded with chemotherapeutic drug doxorubicin (DOX) and NA was prepared using sodium alginate as a matrix. The results showed that SA-DOX-NA had good in situ gel-forming ability and formed a mesh structure that could realize the co-loading of DOX and NA as well as the slow drug release. The electron microscopy results showed that SA-DOX-NA had good in situ gel-forming ability with good internal connectivity, and the three-dimensional mesh structure could realize the co-loading of DOX and NA as well as the slow drug release. The antitumor and immunomodulatory results showed that SA-DOX-NA both effectively inhibited the growth of tumor cells and efficiently promoted the proliferation and activation of DC2.4 dendritic cells without additional adjuvant. In summary, SA-DOX-NA exerts the dual efficacy of chemotherapy and immunotherapy for tumor treatment, and has a good application prospect in local tumor treatment.

Objective To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS).Methods The pretreatment conditions of solid phase extraction(SPE)were op-timized by orthogonal experimental design and the surface water samples were concentrated and ex-tracted by Oasis? HLB and Oasis? MCX SPE columns in series.The extracts were separated by Kine-tex? EVO C18 column,with gradient elution of 0.1%formic acid aqueous solution and 0.1%formic acid methanol solution.Q-TOF-MS'fullscan'and'targeted MS/MS'modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion,prod-uct ion and retention times.Results The 34 emerging contaminants exhibited good linearity in the con-centration range respectively and the correlation coefficients(r)were higher than 0.97.The limit of de-tection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%.The intra-day precision was 0.78%-18.70%.The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected,with a concentration range of 1.93-157.71 ng/L.Conclusion The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.

Objective To investigate the effect of amygdalin(AD)on fracture healing in osteoporotic(OP)rats and its possible mechanism.Methods SD rats were randomly divided into sham group,model group,inhibitor group and low,medium,high dose experimental groups,12 rats in each group.The OP rat model was established by bilateral ovariectomy.After the model was successfully established,rats in low,medium and high dose experimental groups were intraperitoneally injected with 0.1,0.5 and 1.0 mg·kg-1 AD;the inhibitor group was intraperitoneally injected with 5.0 mg·kg-1 H-89[cyclic adenosine monophosphate/protein kinase A/cyclic adenosine monophosphate response element binding protein(cAMP/PKA/CREB)pathway inhibitor]+1.0 mg·kg-1 AD;sham group and model group were intraperitoneally injected with the same amount of 0.9％NaCl,once a day for 90 days.Micro-computer tomography was applied to observe the microstructure of the epiphysis in rats;the biomechanical status of femur was evaluated by orthopedic biomechanical test;the contents of serum osteocalcin(OC),C-terminal telopeptides of type Ⅰ collagen(CTX-Ⅰ),bone morphogenetic protein 2(BMP-2)and cAMP were detected by enzyme-linked immunosorbent assay(ELISA);the level of oxidative stress products in rat serum was detected by kit;Western blot was used to detect the expression of alkaline phosphatase(ALP)and cAMP/PKA/CREB signaling pathway protein(p-PKA/PKA,p-CREB/CREB)in rat bone tissue.Results The bone mineral density of sham group,model group and low,medium,high dose experimental groups,inhibitor group were(251.54±15.41),(135.82±10.92),(173.57±12.65),(204.31±14.48),(235.62±11.37)and(187.83±13.64)mg·cm-3;the contents of cAMP were(0.85±0.06),(0.20±0.03),(0.34±0.07),(0.48±0.09),(0.81±0.12)and(0.57±0.06)μmol·L-1;the expression of p-PKA/PKA were 0.96±0.08,0.06±0.02,0.35±0.04,0.67±0.07,0.94±0.09 and 0.37±0.05;p-CREB/CREB protein were 0.92±0.12,0.04±0.01,0.28±0.03,0.59±0.06,0.91±0.10 and 0.29±0.04,respectively.There were significant differences in the above indexes between sham group and model group,between low,medium,high dose experimental groups and model group,between inhibitor group and high dose experimental group(all P＜0.05).Conclusion AD can reduce oxidative stress,promote fracture healing and alleviate OP symptoms in rats.The mechanism may be related to the activation of cAMP/PKA/CREB signaling pathway.

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Objective To observe the effects of Tianma Gouteng Decoction combined with magnesium sulfate and Labetalol on lowering blood pressure and improving hemorheology in patients with gestational hypertension.Methods Ninety patients with gestational hypertension of liver-yang hyperactivity type were randomly divided into the combination group and the control group,with 45 cases in each group.The control group was treated with magnesium sulfate combined with Labetalol,and the combination group was treated with Tianma Gouteng Decoction on the basis of treatment for the control group.The course of treatment lasted for 5 days.The changes of systolic blood pressure(SBP),diastolic blood pressure(DBP),urinary protein level,and hemorheological indicators of the two groups were observed before and after the treatment.Moreover,the adverse pregnancy outcomes,adverse reactions,and patients'satisfaction of the two groups were compared.Finally,the influencing factors of patients'adverse pregnancy outcomes were investigated by logistic regression analysis.Results(1)After treatment,the SBP,DBP and urinary protein level of patients in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the combination group was significantly superior to that in the control group(P＜0.01).(2)After treatment,the hemorheological indicators of plasma viscosity,whole blood viscosity and hematocrit of patients in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the combination group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)The total incidence of adverse pregnancy outcomes in the combination group was 11.11%(5/45),which was significantly lower and that in the control group(33.33%,15/45),the difference being statistically significant(P＜0.05).(4)The patients'satisfaction of the combination group was 97.78%(44/45),which was significantly higher than that of the control group(84.44%,38/45),and the difference was statistically significant(P＜0.05).(5)The total incidence of adverse reactions in the combination group was 13.33%(6/45)and that in the control group was 8.89%(4/45),but the intergroup comparison showed no significant difference between the two groups(P＞0.05).(6)Logistic regression analysis of influencing factors showed that no medication of Tianma Gouteng Decoction combined with Labetalol and magnesium sulfate,and poor antihypertensive effect were the independent risk factors for adverse pregnancy outcomes in patients with gestational hypertension(all OR＞1,P＜0.05).Conclusion Tianma Gouteng Decoction combined with magnesium sulfate and Labetalol in treating gestational hypertension exerts certain antihypertensive effect,and the therapy can effectively improve the hemorheological indicators and the adverse pregnancy outcomes,and enhance the patients'satisfaction.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective:To investigate the molecular mechanism and distribution characteristics of RhD negative phenotypes in Han population of blood donors in Wuhu city.Methods:A total of 210 RhD-samples from August 2021 to August 2022 were screened by serological test and collected from Wuhu Central Blood Station for the voluntary blood donor population.Exons 1 and 10 of the RHD gene were amplificated by PCR to determine whether the samples had the RHD gene.Exons 1-10 of the RHD gene were amplificated by PCR and zygosity analysis were performed in 82 samples containing D gene,and Sanger sequencing was performed on 55 samples containing all RHD exons to determine the genotype.Results:Among 210 RhD-specimens,128 cases(60.38％)had RHD gene deletion.27 cases had partial exons of RHD,including 2 cases with RHD*DVI.3/RHD*01N.01,24 cases with RHD*01N.04/RHD*01N.01,and 1 case with RHD-CE(2-10)/RHD*01N.01.55 cases had retained all of 10 exons,including 4 cases with RHD*01/RHD*01N.01,6 cases with RHD*15/RHD*01N.01,1 case with RHD*01W.72/RHD*01N.01,1 case with RHD*15/RHD*01EL.01,39 cases with RHD*01EL.01/RHD*01N.01,and the remaining 4 cases were determined to have no RHD gene deletion by zygosity analysis and sequencing showed the presence of 1227G＞A mutation loci.Conclusion:There is polymorphism in the molecular mechanism of RhD-D gene in Wuhu blood donor population,among which RHD*01EL.01 and RHD*15 are the main variants in this region.The results of this study provide a theoretical basis for RhD blood group identification and clinical blood transfusion in this region.

Aim To compare the pharmacokinetics of pemirolast potassium tablets in healthy subjects in Chi-na under single fasting and postprandial conditions,and to evaluate the bioequivalence of the test prepara-tion(T)and the reference preparation(R).Methods A randomized,open-ended,single-dose,two-cycle,double-cross bioequivalence trial design was adopted,and 26 and 30 subjects were enrolled in the fasting group and the postprandial group,respectively,and 10 mg of the test preparation and the reference preparation were taken in the fasting or postprandial state each cy-cle,and venous blood was collected at the designed time points before and after the administration cycle.The concentration of pemirolast potassium in plasma was determined by LC-MS/MS method,and the phar-macokinetic parameters were calculated with PhoenixTM WinNonlin ?(8.3)software,and the bioequivalence analysis of the two preparations was performed.Re-sults The t1/2 of the test preparation and the reference preparation was(4.44±0.91)h and(4.49±0.93)h,respectively;the median tmax was(1.96±1.29)h and(2.18±1.25)h,respectively;the Cmax was(867.12±205.56)μg·L-1 and(863.35±172.03)μg·L-1,respectively;the AUC0-t was(5 513.23±1463.67)h·μg·L-1 and(5 661.32±1 628.65)h·μg·L-1,respectively;AUC0_∞ was(5 699.81±1477.68)h·μg·L-1 and(5 849.44±1 644.75)h·μg·L-1,respectively.The statistical results of the 90％confidence intervals of the main pharmacokinetic parameters Cmax,AUC0-t,and AUC0-∞ was 92.49％～107.53％,94.71％～100.67％and 95.28％～100.27％,respectively,all of which were within the range of 80.00％～125.00％,and the safety of the tested preparation and the reference preparation was good when taken orally on an empty stomach.The t1/2 of single oral administration after prandial administra-tion of the tested preparation and the reference prepara-tion was(4.46±0.78)and(4.51±0.84)h,respec-tively;the median tmax was(3.08±1.36)h and(3.28±1.28)h,respectively;the Cmax was(683.83±111.87)μg·L-1 and(689.77±110.24)μg·L-1,respectively;the AUC0-t was(5 695.99±1566.05)h·μg·L-1 and(5 773.60±1 551.04)h·μg·L-1,respectively;the AUC0-∞ was(5 914.06±1 551.86)h·μg·L-1 and(5 967.30±1552.89)h·μg·L-1,respectively.The 90％confi-dence interval of Cmax,AUC0-t,and AUC0-∞ was 93.56％～104.69％,96.43％～100.83％,and 97.29％～101.14％,respectively,which was in the range of 80.00％～125.00％,and the safety of the tested preparation and the reference preparation was good after meals.Conclusion In the state of fasting and postprandial single oral administration,the two kinds of pemirolast potassium tablets have good bio-equivalence.

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.
Male ; Female ; Humans ; Child ; Fanconi Anemia/genetics* ; Chromosome Breakage ; Retrospective Studies ; Exons ; China/epidemiology*