OBJECTIVETo study the preventive and therapeutic effects of total saponin of Dioscorea (TSD) on chronic hyperuricemia, and its effect on urate transporter 1 (URAT1) in rats.

METHODNinety male rats were randomly divided into 6 groups: the normal group, the model group, TSD high-, medium- and low-dose (300, 100, 30 mg x kg(-1)) groups and the benzbromarone (10 mg x kg(-1)) group. Potassium oxonate and ethambutol were adopted to establish the chronic hyperuricemia model Since the third week, all the rats were intragastrically administered with drugs for 4 weeks, once a day, in order to determine their uric acid in serum and urine, uric acid excretion and xanthine oxidase (XOD). URAT1 mRNA and URAT1 protein expression in rat renal tubular cells were determined by RT-PCR and immunohistochemistry method respectively.

RESULTSerum uric acid level of the model group increased significantly, while uric acid excretion decreased, with high expressions of renal URAT1 mRNA and URAT1 protein. TSD could dose-dependently reduce the serum uric acid level of chronic hyperuricemia rats, increase the concentration of uric acid and uric acid excretion in urine, and reduce renal URAT1 mRNA and URAT1 protein expression. Its effects were similar with that of benzbromarone, but with no significant effect on XOD and urinary volume of chronic hyperuricemia rats.

CONCLUSIONTSD has an obvious effect of anti-hyperuricemia It may reduce the reabsorption of uric acid by inhibiting the high expression of rat renal URAT1.

Animals ; Anion Transport Proteins ; biosynthesis ; genetics ; metabolism ; Benzbromarone ; pharmacology ; Dioscorea ; chemistry ; Gout Suppressants ; chemistry ; pharmacology ; Hyperuricemia ; blood ; drug therapy ; genetics ; urine ; Kidney Tubules ; drug effects ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Saponins ; chemistry ; pharmacokinetics ; pharmacology ; Uric Acid ; blood ; urine ; Xanthine Oxidase ; metabolism

Based on the professional characteristics and nature of ophthalmology special examination and combined with teaching requirements for optometry foreign students, we developed a targeted teaching plan and practiced the classification teaching. Using guided trilogy teaching, we guided students to identify and analyze the similarities and differences between the image and the special examination function exami-nation results, emphasizing the cultivation of clinical ophthalmology diagnostic thinking of students, and we obtained good teaching and practice effect.

Objective To investigate the effects of mercury on T lymphocytes and serum immune indexes of workers with Methods occupational mercury exposure. A total of 45 workers with occupational mercury exposure were selected as the ， mercury exposure group and 47 workers without occupational mercury exposure were selected as the control group using the judgment sampling method. Cold atomic absorption spectrometry was used to detect the urinary mercury level of the two groups. （ ） +， + +， + + - + Flow cytometry was used to detect the proportion of cluster of differentiation CD 3 CD3CD4 CD3CD8 and CD3CD19 ， - （ - ） - （ - ） cells in peripheral blood and the levels of tumor necrosis factor α TNF α and interleukin 8 IL 8 in serum. The levels of （ ） ， Results immunoglobulin Ig A IgG and IgM in serum were measured by immune nephelometry. The urinary mercury level of （ ： vs ，P ） individuals in the mercury exposed group was higher than that of the control group median 92.7 13.2 μg/g Cr <0.01 . The +， + +， - + proportion of CD3 CD3CD4 CD3CD19 cells in peripheral blood and serum IgG level in the mercury exposed group （ P ）， - - （ P ） decreased all <0.05 and the serum TNF α and IL 8 levels increased all <0.01 compared with the control group. Urinary - + mercury level was negatively correlated with the proportion of CD3CD19 cells in peripheral blood and serum IgG level in the ［ （r） ， ， P ］， study subjects Spearman correlation coefficient S were −0.21 and −0.31 respectively all <0.05 and positively - - （r ， ， P ） ， correlated with serum TNF α and IL 8 levels S were 0.36 and 0.39 respectively all <0.05 . However the urinary mercury （ P ）， +， + +， level was neither correlated with IgA and IgM levels in serum all >0.05 nor with the proportion of CD3 CD3CD4 + + （ P ） Conclusion CD3CD8 cells in peripheral blood all >0.05 . Occupational exposure to mercury can lead to abnormal ， changes in peripheral blood T lymphocyte subsets B lymphocytes and serum immune factors in workers. The mercury load of occupational mercury exposure workers may impact their immune function.

Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.
Antibodies, Monoclonal ; pharmacokinetics ; Cytotoxins ; pharmacokinetics ; Humans ; Immunoconjugates ; pharmacokinetics ; Neoplasms ; drug therapy

AIMTo identify a novel alternative transcript of the novel retinal pigment epithelial cell gene (NORPEG) expressed in the human testis.

METHODSA human testis cDNA microarray was established and hybridized with cDNA probes from human fetal testes, adult testes and human spermatozoa. Differentially expressed clones were sequenced and analyzed. One of these clones was a short transcript of NORPEG which we proceeded to analyze by RT-PCR.

RESULTSThe novel short alternative transcript of NORPEG was isolated and named sNORPEG. It was 3486 bp in length and contained a 2952-bp open reading frame, encoding a 110.4-kDa protein of 983 amino acids. Amino acid sequence analysis showed that the sNORPEG protein contains six ankyrin repeats and two coiled-coil domains. It shares a high homology with the NORPEG and ankycorbin proteins in both its sequence and motifs. Blasting the human genome database localized sNORPEG to human chromosome 5p13.2-13.3. Expression profiles showed that sNORPEG was expressed in human fetal testes, adult testes and spermatozoa. Moreover, sNORPEG was found to be ubiquitously expressed in human tissues.

CONCLUSIONsNORPEG is expressed in different developmental stages of the testis and encodes a protein that may have roles in human testis development and spermatogenesis.

Alternative Splicing ; Amino Acid Sequence ; Base Sequence ; Cytoskeletal Proteins ; genetics ; DNA, Complementary ; Gene Expression Profiling ; Humans ; Male ; Molecular Sequence Data ; Open Reading Frames ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Homology, Amino Acid ; Testis ; metabolism ; Transcription Factors ; genetics

OBJECTIVETo investigate the ectopic grafts of mouse testicular cells by observing the reconstruction of seminiferous tubules, colonization of spermatogenic cells and spermatogenesis using immunodeficient mice as recipients.

METHODSThe testes of newborn male ICR mice were digested to obtain single cell suspension. The cells were then mixed with matrigel and subcutaneously grafted into the dorsal region of the male nude mice. The mice were castrated after the operation and the grafts were dissected from 5 of the nude mice at 4, 6, 8 and 10 weeks, respectively. The success rates of transplantation and the graft diameters were calculated, and the structure of the reconstituted seminiferous tubules, colonization of the germ cells and spermatogenesis were observed by HE staining and immunohistochemistry.

RESULTSAll the mice recipients survived after the testicular cell transplantation. Within 10 weeks after the operation, tissue masses could be observed, with the diameter increased from (3.91 +/- 0.71) mm at 4 weeks to (6.69 +/- 0.50) mm. Neovascularization was detected at the surface of the masses and seminiferous tubule structures found in the grafts. The germ cells that developed from spermatogonia to round spermatids were observed, but with no sperm in the tubules. Germ cells, Sertoli cells and Leydig cells were identified by immunochemical detection of Mvh, Gata4 and P450Scc in the grafts at 8 weeks.

CONCLUSIONSeminiferous tubules could be ectopically reconstructed from suspension of neonatal mouse testicular cells. Ectopic grafting provided a preferable model for the studies on testis tissue engineering and interactions between testicular cells during testicular development and spermatogenesis.

Animals ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Mice, Nude ; Seminiferous Tubules ; cytology ; Sertoli Cells ; cytology ; transplantation ; Spermatids ; cytology ; Spermatogenesis ; Testis ; cytology ; transplantation ; Transplantation, Heterologous

Diabetic peripheral neuropathy is a common complication of diabetes， and its pathogenesis is complex. Its high morbidity can result in disability， teratogenesis， and death in diabetic patients. At present， the pathogenesis of diabetic peripheral neuropathy has not been clearly elucidated， which may be related to oxidative stress， inflammatory response， microcirculation dysfunction， metabolic abnormalities， etc. Recent studies have found that apoptosis plays an important role in the pathogenesis of diabetic peripheral neuropathy. The three pathways， i.e.， mitochondrial pathway， death receptor pathway， and endoplasmic reticulum pathway， jointly regulate the cell apoptosis in the body. Traditional Chinese medicine， with definite efficacies in the treatment of diabetic peripheral neuropathy， is advantageous in overall regulation and multi-target and multi-pathway treatment. As reported， the active ingredients in Chinese medicine and Chinese medicinal compounds can alleviate diabetic peripheral neuropathy by regulating apoptosis signaling pathways. Furthermore， apoptosis pathways are expected to be potential targets for new drugs against diabetic peripheral neuropathy following oxidative stress. Therefore， this paper， taking apoptosis as the entry point， reviewed the research progress on TCM intervention in diabetic peripheral neuropathy in recent years to provide references for the clinical prevention and treatment of diabetic peripheral neuropathy and the development of new drugs.

Objective: To study the chemical constituents of Bletillae Formosanae Rhizoma and the distribution characteristics of active components in the fingerprint by establishing its high performance liquid chromatography (HPLC) fingerprints. Method: HPLC was used to establish the fingerprint of Bletillae Formosanae Rhizoma. Four reference substances,i.e. militarine,coelonin,4-methoxy-9,10-dihydrophenanthrene-1,2,7-triol and batatasin Ⅲ were used to identify chromatographic peaks. The fingerprints of 17 batches of Bletillae Formosanae Rhizoma fingerprints were analyzed and compared by "Computer-aided-similarity evaluation soft" and stoichiometry,and then compared with the fingerprint of Bletillae Rhizoma. Result: The established HPLC fingerprint method of Bletillae Formosanae Rhizoma showed good repeatability and stability. 20 common peaks were marked,four of which were identified by reference substances; militarine was No.8 common peak,and others corresponded to No. 10, No. 14 and No. 18 common peaks. Results showed that the similarities of samples except S4 were higher than 0.85, but the relative peak area of common peaks was quite different. Within the cluster distance 10,the samples are clustered into 5 categories, reflecting certain origin correlation. Principal component analysis (PCA) showed that the difference in samples was mainly caused by the common peaks located after No. 9 peak,where chemical constituents such as bibenzyl and dihydrophenanthrene were distributed. Bletillae Formosanae Rhizoma and Bletillae Rhizoma showed similar chemical constituents. Conclusion: The method provided a theoretical basis for the further clinical application and quality control of Bletillae Formosanae Rhizoma,as a substitute for Bletillae Rhizoma.

Objective: To evaluate the model with spleen deficiency and dampness stagnancy by bioelectrical impedance analysis (BIA) and traditional indicators. Method: The forty rats were divided into blank group and model group, with 20 rats in each group. The rats in the blank group were fed with normal feed, the rats in model group were prepared with the spleen deficiency and dampness stagnancy model for 14 days. Observe the general condition of the rats, measure the water content of the feces in the dry method, measure the water load index by weighing method, and detect the urinary D-xylose excretion total protein (TP), albumin (Alb) content, by enzyme-linked immunosorbent assay (ELISA). Western blot analysis of renal aquaporin 1 (AQP1) content, and the use of experimental animal body composition analyzer to determine the total water content (TBW), extracellular fluid (ECF), intracellular fluid (ICF), fat mass (FM), free fat mass (FFM) and body mass bioelectrical impedance index such as body mass index (BMI). Result: Compared with blank group, the rats in model group lost weight, gradually loose stools occasionally, the anus temperature was basically unchanged, body mass, D-xylose excretion, water load index, TP and Alb content decreased (P<0.01). The feces contained water,the rate and the content of AQP1 in the renal pulp were increased (P<0.01). The TBW, ECF and FFM were increased, and the ICF, FM and BMI were decreased (P<0.01). Conclusion: Rats with spleen deficiency and dampness stagnancy induced a combination of factors such as diet and excessive fatigue. The bioelectrical impedance method can be more intuitive and comprehensive.

Objective: To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI). Methods: This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1^st, 2019 to December 31^st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results: A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) (OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above (OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above (OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion: There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.
Infant ; Male ; Infant, Newborn ; Humans ; Female ; Prospective Studies ; Congenital Hypothyroidism/epidemiology* ; Risk Factors ; Infant, Very Low Birth Weight ; Birth Weight ; Gestational Age ; Retinopathy of Prematurity/epidemiology* ; Infant, Newborn, Diseases ; Hospitals