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Objective: To analyze the genus, drug resistance/virulence and phylogenetic characteristics of Brucella strains isolated from brucellosis surveillance sentinels in Henan Province from 2013 to 2022, and provide baseline data for the surveillance, early warning and outbreak tracing of brucellosis. Methods: Blood samples were collected from patients with Brucella infection for strain isolation, culture and species identification, drug susceptibility test, whole genome sequencing, splicing and assembly, functional/virulence/resistance gene prediction analysis and phylogenetic tree drawing based on single nucleotide polymorphism (SNP). Results: In 36 brucellosis patients, the majority were men (86.11%, 31/36), young adults aged 18-50 (88.89%, 32/36) and farmers/herdsmen (72.22%, 26/36). A total of 36 strains of Brucella melitensis were isolated, and average 1 305 functional proteins of 21 categories were predicted by strain genome; all the strains carried four main virulence factors (pmm, VirB group, BtpA/BtpB, BvrS/BvrR). The drug sensitivity rate was 100.00% to six types of antibiotics including levofloxacin, rifampicin, doxycycline, streptomycin, tetracycline and gentamicin, they showed different resistances to three antibiotics including compound trimethoprim-sulfamethoxazole, ciprofloxacin and ampicillin. The strains carried four types of resistance genes and two clusters of resistance genes, with four combinations of genotypes, the resistance mechanisms included antibiotic degradation/modification enzymes, resistant nodular cell differentiation (RND) efflux pumps, 16S/23S ribosomal rRNA binding site mutations, etc . The number of SNP differed in the genomes of 36 Brucella melitensis strains ranged from 0 to 454 and phylogenetic tree was divided into three major branches, with relative branch distances between 0.000 0 and 0.498 6 for each strain. Conclusions: Human Brucella melitensis strains isolated from surveillance sentinels in Henan from 2013 to 2022 carried multiple virulence and antibiotic resistance genes and had different drug resistance phenotypes. Single nucleotide polymorphism analysis and phylogenetic tree analysis showed significant differences in phylogenetic relationships among different strains.

Background: As research on diabetes continues to advance, more complex classifications of this disease have emerged, revealing the existence of special types of diabetes, and many of these patients are prone to misdiagnosis and underdiagnosis, leading to treatment delays and increased health care costs. The purpose of this study was to identify four causes of secondary diabetes., Case Summary: Secondary diabetes can be caused by various factors, some of which are often overlooked. These factors include genetic defects, autoimmune disorders, and diabetes induced by tumours. This paper describes four types of secondary diabetes caused by Williams-Beuren syndrome, Prader-Willi syndrome, pituitary adenoma, and IgG4-related diseases. These cases deviate significantly from the typical progression of the disease due to their low incidence and rarity, often leading to their neglect in clinical practice. In comparison to regular diabetes patients, the four individuals described here exhibited distinct characteristics. Standard hypoglycaemic treatments failed to effectively control the disease. Subsequently, a series of examinations and follow-up history confirmed the diagnosis and underlying cause of diabetes. Upon addressing the primary condition, such as excising a pituitary adenoma, providing glucocorticoid supplementation, and implementing symptomatic treatments, all patients experienced a considerable decrease in blood glucose levels, which were subsequently maintained within a stable range. Furthermore, other accompanying symptoms improved., Conclusion: Rare diseases causing secondary diabetes are often not considered in the diagnosis of diabetes. Therefore, it is crucial to conduct genetic tests, antibody detection and other appropriate diagnostic measures when necessary to facilitate early diagnosis and intervention through proactive and efficient management of the underlying condition, ultimately improving patient outcomes., Competing Interests: Conflict-of-interest statement: All the authors declare no conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The correlation between the increased mean platelet volume and varicocele is controversial., Objectives: We designed this research to demonstrate the correlation relationship between varicocele and mean platelet volume by studying the changes of mean platelet volume in patients with varicocele before and after operation., Materials and Methods: A total of 317 patients with left unilateral varicocele underwent operation, and 293 healthy adult males were enrolled in the study. We collected diagnostic data for preoperative patients through physical examination, color Doppler ultrasonography, and blood routine, and recorded the follow-up data at 6 months after operation for varicocele. Platelet indices and the degree of varicocele or the diameter of spermatic vein correlation analysis were performed. Mean platelet volume values of preoperative and 6-month postoperative were statistically evaluated., Results: We found that the degree of varicocele and the diameter of spermatic vein were positively correlated with mean platelet volume (p = 0.001 or p < 0.001). When the left unilateral varicocele patients and healthy subjects were compared, there was a significant increase in mean platelet volume (p = 0.003). Mean platelet volume values of 96 varicocele patients who were cured by operation for varicocele after 6 months were decreased significantly more than preoperative (p = 0.039), but 32 varicocele patients of 6-month postoperative recurrence could not prove this change (p = 0.930)., Discussion and Conclusion: Our research proves that mean platelet volume was positively correlated with the degree of varicocele and the diameter of spermatic vein and varicocele patients showed significantly higher mean platelet volume than healthy subjects. The mean platelet volume of varicocele patients cured by operation for varicocele after 6 months was lower than before, but there was no difference in mean platelet volume between 6-month postoperative recurrent patients with preoperative., (© 2019 American Society of Andrology and European Academy of Andrology.)

Cells require some metals, such as zinc and manganese, but excess levels of these metals can be toxic. As a result, cells have evolved complex mechanisms for maintaining metal homeostasis and surviving metal intoxication. Here, we present the results of a large-scale functional genomic screen in Drosophila cultured cells for modifiers of zinc chloride toxicity, together with transcriptomics data for wild-type or genetically zinc-sensitized cells challenged with mild zinc chloride supplementation. Altogether, we identified 47 genes for which knockdown conferred sensitivity or resistance to toxic zinc or manganese chloride treatment, and >1800 putative zinc-responsive genes. Analysis of the 'omics data points to the relevance of ion transporters, glutathione (GSH)-related factors, and conserved disease-associated genes in zinc detoxification. Specific genes identified in the zinc screen include orthologs of human disease-associated genes CTNS, PTPRN (also known as IA-2), and ATP13A2 (also known as PARK9). We show that knockdown of red dog mine (rdog ; CG11897) , a candidate zinc detoxification gene encoding an ABCC-type transporter family protein related to yeast cadmium factor (YCF1), confers sensitivity to zinc intoxication in cultured cells, and that rdog is transcriptionally upregulated in response to zinc stress. As there are many links between the biology of zinc and other metals and human health, the 'omics data sets presented here provide a resource that will allow researchers to explore metal biology in the context of diverse health-relevant processes., (Copyright © 2018 Mohr et al.)

The potential influence of dietary phytoestrogen exposure on human health during different life phases including early childhood is a matter of scientific debate. In order to improve the risk-benefit assessment of exposure to dietary phytoestrogen, reliable and age-stratified exposure data are desirable. For contributing to the database on phytoestrogen exposure, in the present study plant-derived foods from the Chinese market were analysed by LC-MS/MS for their contents of phytoestrogens, including daidzein, genistein, secoisolariciresinol, glycitein and coumestrol. The analytical data showed the presence of phytoestrogens in a concentration range of less than 0.1 to about 50 μg g(-1). Dietary intake was assessed on the basis of average food intake data obtained from interviewing 1000 randomly selected people with the help of food frequency questionnaires. Based on the overall population sampled, the average total phytoestrogen intake was estimated at 232 μg kg(-1) day(-1). Genistein contributed to about 66%, secoisolariciresinol and glycitein to about 10% each, and daidzein to about 7% of the overall intake. Coumestrol was present only in trace amounts. Age-related exposure assessment indicated that pre-pubertal children (aged 0-14 years) were exposed at the highest level with an average total phytoestrogen intake of 621 μg kg(-1) day(-1). The substantially higher average exposure of children as compared with adults should trigger further research into the potential health effects of early life exposure to phytoestrogen.

Objective: To observe the clinical effect of low-dose testosterone undecanoate capsules combined with tadalafil on late-onset hypogonadism (LOH) accompanied with ED., Methods: Ninety cases of LOH accompanied with ED who met the inclusion criteria were randomly divided into a control group and a combination therapy group, the former treated with tadalafil and the latter with low-dose testosterone undecanoate capsules combined with tadalafil. The LOH symptoms, IIEF-5 scores, sexual encounter profile (SEP) scores, prostate volumes, and the levels of total testosterone (TT), free testosterone (FT) and prostatic specific antigen (PSA) were recorded and compared between the two groups before and after treatment., Results: The IIEF-5 and SEP scores and the TT and FT levels were 20.6 +/- 3.8, 4.02 +/- 1.08, (15.4 +/- 3.4) nmol/L and (0.391 +/- 0.062) nmol/L, respectively, in the combination therapy group after treatment, significantly higher both than 15.7 +/- 3.9, 1.49 +/- 0.82, (10.1 +/- 1.2) nmol/L and (0.200 +/- 0.045) nmol/L before treatment (P < 0.01) and than 8.6 +/- 3.6, 3.50 +/- 1.21, (10.2 +/- 1.2) nmol/L and (0.210 +/- 0.051) nmol/L in the control group after treatment (P < 0.01)., Conclusion: Low-dose testosterone undecanoate capsules combined with tadalafil has a definite clinical effect and no obvious adverse reactions in the treatment of LOH accompanied with ED.

Objective: To investigate the effect of low-dose daily de-escalatory administration of tadalafil on psychological erectile dysfunction (ED)., Methods: We randomized 84 psychological ED patients into an observation and a control group of equal number to receive low-dose daily de-escalatory administration and on-demand medication of tadalafil, respectively, both for 2 months. We compared the scores on IIEF-5 and erection hardness (EHS) between the two groups before and after the treatment., Results: The treatment and follow-up were accomplished for 79 cases, with 5 withdrawals in the control group. The IIEF-5 and EHS scores were remarkably improved in both the observation and control groups after treatment. The rate of therapeutic effectiveness was significantly higher in the observation group than in the control (95.2% vs 86.5%, P < 0.05)., Conclusion: Low-dose daily de-escalatory administration of tadalafil is highly effective and even better than on-demand medication of tadalafil for psychological ED.

Objective: To evaluate the clinical effects of Compound Xuanju Capsule combined with tamoxifen citrate on the seminal parameters of men with idiopathic oligozoospermia., Methods: We equally assigned 120 men with idiopathic oligozoospermia to receive Compound Xuanju Capsule plus tamoxifen citrate (experiment group) or tamoxifen citrate alone (control group). After 3 months of medication, we compared the concentration and total number of sperm with the baseline, and analyzed the influence of the duration of natural infertility on the therapeutic effect., Results: Both the concentration and total number of sperm were significantly increased in both the experiment and the control groups after 3 months of medication as compared with the baseline (P < 0.05), and the increases were even more significant in the former than in the latter group (P < 0.05). The therapeutic efficacy was remarkably better in the patients with natural infertility < or = years than in those > 3 years (P < 0.05)., Conclusion: Compound Xuanju Capsule combined with tamoxifen citrate produces satisfactory results in the treatment of idiopathic oligozoospermia, and therefore can be used as a first-line therapy for this disease.

The aim of the present study was to investigate whether oxidative stress and immune dysfunction could be attenuated by Ganoderma atrum polysaccharide (PSG-1) in d-galactose (d-gal)-induced aging mice, and provide evidence for its effects. The results showed that PSG-1 significantly decreased lipid peroxidation in liver, brain, and spleen, but concomitantly increased the activities of superoxide dismutase, catalase, and glutathione peroxidase compared with the d-gal group. Elevation of glutathione contents and attenuation of glutathione disulfide contents were also found in PSG-1-treated animals. Furthermore, the results showed that PSG-1 treatment increased basal lymphocyte proliferation as well as T cell and B cell proliferation and enhanced interleukin-2 production. Taken together, the results suggested that PSG-1 had potential as a novel agent to promote health and improve aging-associated pathologies, at least in part, via modification of the redox system and improvement of immune function.

Objective: To investigate the effect of Jinleng undershorts on the elevated scrotal temperature induced by varicocele as well as on other clinical symptoms of the disease., Methods: Fifty-one varicocele patients received the treatment of wearing Jinleng undershorts for 30 min twice a day for a course of 90 days. Comparisons were made between the scrotal temperatures and other clinical symptoms of varicocele before and after the treatment., Results: After 90 days of treatment with Jinleng undershorts, the left scrotal temperature of the varicocele patients was significantly reduced from (32.16 +/- 0.79) degrees C to (31.53 +/- 0.77) degrees C (P < 0.01), and the right scrotal temperature decreased from (31.91 +/- 0.73) degrees C to (31.81 +/- 0.63) degrees C (P > 0.05). Compared with pretreatment, significant improvement was found in such symptoms as wetness, fever and swelling of the scrotum, backache, headache, dizziness, fatigue and anxiety (P < 0.05), as well as in testicular pain (P < 0.01) and IIEF-5 score, which was increased from 15.89 +/- 6.13 to 20.04 +/- 3.87 (P < 0.01)., Conclusion: Jinleng undershorts can be used for the treatment of mild and moderate varicocele.

Replication-deficient adenovirus (Ad) vectors are effective in transferring genes in vivo, but their use is associated with significant variation in the extent and/or duration of expression observed among different strains of experimental animals and different routes of administration of the vector. We have minimized the variables of the heterologous transgene and animal-to-animal variation by constructing an Ad vector encoding murine thrombopoietin (mTPO, AdmTPO), a homologous protein that induces a physiologic response (elevation of blood platelet levels) that can be followed sequentially over time in the same animal. Using the C57BL/6 and BALB/c stains, liver administration was accomplished by intravenous administration and skeletal muscle administration by direct injection. Despite the use of a homologous cDNA as a transgene, the Ad genome was rapidly lost from the liver after intravenous administration over the first 1 to 2 weeks, with no difference in pattern of decline between the C57BL/6 and BALB/c strains. Both strains exhibited a cytotoxic T lymphocyte (CTL) response directed against the AdmTPO vector. Consistent with the decline in vector genome over time, the initial high levels of mTPO mRNA in the liver declined to an undetectable level within 2 weeks. Platelet counts peaked at 8- to 10-fold above baseline within the first 2 weeks, and then gradually declined, returning to normal level by 50 to 60 days. Intravenous administration of the AdmTPO vector to beta2-microglobulin-deficient mice resulted in a longer persistence of elevated platelets levels, although the eventual return of platelet levels to normal in these mice suggests the elimination of the Ad vector cannot be explained solely by CTL response. Although the intramuscular administration of the AdmTPO vector resulted in platelet levels with a lower peak and minor differences over time compared with the intravenous route, the C57BL/6 and BALB/c strains demonstrated the same rapid loss of Ad genome and mTPO mRNA levels in the muscle as in the liver. Together, these observations suggest that simplifying the experimental design by eliminating the variable of host response to a heterologous transgene, and by following the consequences of gene transfer in the same animals over time, there can be remarkable similarity in strain- and route-dependent responses to an Ad vector.

Effective gene transfer and expression following repetitive administration of adenoviral (Ad) vectors in experimental animals is limited by anti-Ad neutralizing antibodies. Knowing that anti-Ad humoral immunity is serotype-specific, we hypothesized that anti-Ad neutralizing immunity could be circumvented using Ad vectors of different serotypes (Ad2, Ad5) within the same subgroup (C) to transfer and express beta-glucuronidase (beta glu) in the lung. Sprague-Dawley rats received an intratracheal administration of either Ad2 beta glu or Ad5 beta glu, and, 14 days later, repeat administration of either the same vector or a vector of a different serotype. Analysis of serum and bronchoalveolar lavage fluid following initial vector administration demonstrated systemic and local serotype-specific neutralizing antibodies. For both the Ad2 and Ad5 vectors, beta glu expression 24 hr following the second administration of the same serotype was < 30% of that of naive animals. In contrast, beta glu expression 24 hr following second administration of a different serotype Ad vector was similar to expression at 24 hr of naive animals receiving a single administration (Ad5 beta glu followed by Ad2 beta glu, as well as Ad2 beta glu followed by Ad5 beta glu; p > 0.2 both comparisons). Although the alternative serotype bypassed anti-Ad neutralizing immunity, persistence of expression was reduced compared to that following administration to naive animals. Compatible with this observation, systemic administration of the same vectors to C57B1/6 mice demonstrated induction of cytotoxic T lymphocytes directed against the beta glu transgene, as well as products of the Ad genome. Interestingly, intratracheal administration of vectors with different serotypes and different transgenes to rats resulted in longer expression (but still not normalized) compared to that achieved with vectors of different serotypes but the same transgene. These observations demonstrate that alternate use of Ad vectors from different serotypes within the same subgroup can circumvent anti-Ad humoral immunity to permit effective gene transfer after repeat administration, although the chronicity of expression is limited, likely by cellular immune process directed against both the transgene and viral gene products expressed by the vector.

Based on the hypothesis that tissue macrophages present an obstacle for adenovirus (Ad) vector-mediated gene transfer to internal organs, this study evaluated the consequences of transient depletion of Kupffer cells on subsequent transfer of the Ad vector genome and Ad vector-directed gene expression in the livers of experimental animals. Depletion of Kupffer cells in mice by intravenous administration of multilamellar liposomes containing dichloromethylene-bisphosphonate permitted subsequent intravenous administration of an Ad vector to provide a higher input of recombinant adenoviral DNA to the liver, an absolute increase in transgene expression, and a delayed clearance of the vector DNA and transgene expression. These observations suggest that the tissue macrophages pose a significant hurdle to Ad vector-mediated gene transfer and that strategies to transiently suppress macrophage defenses might be useful in enhancing the efficiency of this in vivo gene transfer system.