Japan is one of the main trading partners for the import and export of experimental animals in China,and its quarantine and supervision policies for the import and export of experimental animals are very detailed and strict.This article takes experimental dogs,cats,and monkeys as examples to provide an in-depth analysis of the quarantine and supervision policies for the main experimental animals exported to Japan.At the same time,it reflects on the current laws and regulations,import and export management method,standards,biosafety,breeding and management status,as well as the import and export business status of experimental animals in China.Suggestions are provided in improving the laws and regulations,import and export management method,ensuring national biosafety,improving the management level of experimental animal breeding,and promoting the import and export trade of experimental animals,in order to provide reference for comprehensively improving the production,use,and breeding management level of experimental animals in China and strengthening the trade between China and Japan.

Objective:To investigate urinary pH distribution and its influencing factors in gout patients, to provide insights for individualized treatment.Methods:This is a retrospective study. The gout patients in the Gout Outpatient Department of the Affiliated Hospital of Qingdao University from September 2019 to August 2021 were collected. Clinical data were collected and relevant indicators were measured. The patients were divided into different groups according to urinary pH. Clinical characteristics and factors related to urinary pH were compared among the groups. SPSS 23.0 software was used.Results:A total of 2 553 patients were enrolled. There were significant statistical differences in age, body mass index, triglyceride, alanine aminotransferase(ALT), blood urea nitrogen, serum creatinine, estimated glomerular filtration rate(eGFR), blood uric acid, urinary uric acid/creatinine ratio, fraction excretion of uric acid(FEUA) among groups with different urinary pH( F were 5.114, 4.772, 7.170, 4.721, 13.603, 2.812, 3.422, 22.834, 18.230, 26.332, all P<0.05). Urinary uric acid and FEUA in acute group were higher than those in remission group( Z were -2.295, -3.528, both P<0.05). After adjusting for gender, age, eGFR, logistics regression analysis showed that body mass index, triglyceride, total cholesterol, ALT, blood uric acid, and blood urea nitrogen were still risk factors. Multivariate logistic regression analysis showed that triglyceride, blood uric acid, and blood urea nitrogen were independent risk factors associated with acid urine. Linear correlation analysis showed that urinary pH was negatively correlated with body mass index, triglyceride, total cholesterol, blood uric acid, fasting glucose, blood urea nitrogen, ALT( r were -0.079, -0.106, -0.051, -0.186, -0.040, -0.122, -0.051, all P<0.05), but positively correlated with eGFR( r=0.058, P=0.003). Conclusion:The overall urine pH levels in patients with primary gout are below normal reference. Several metabolic components are related to it. Triglyceride, blood uric acid, and blood urea nitrogen are independent risk factors of acidic urine. In clinical practice, attention should be paid to timely alkalization of urine to prevent complications.

Diabetes mellitus (DM) is a major metabolic disease endangering global health, with diabetic nephropathy (DN) as a primary complication lacking curative therapy. Sporoderm-broken spores of Ganoderma lucidum (GLP), an herbal medicine, has been used for the treatment of metabolic disorders. In this study, DN was induced in Sprague-Dawley rats using streptozotocin (STZ) and a high-fat diet (HFD), and the protective mechanisms of GLP were investigated through transcriptomic, metabolomic, and network pharmacology (NP) analyses. Our results demonstrated that GLP intervention ameliorated renal damage and inflammation levels in DN rats. Integrative metabolomic and transcriptomic analysis revealed that GLP treatment modulated glucose and cellular energy metabolisms by regulating relevant genes. GLP significantly suppressed the inflammations by impacting glucose and energy metabolism-related gene expression (Igfbp1 and Angptl4) and enhanced metabolic biomarkers of 4-Aminocatechol. In addition, NP analysis further indicated that GLP may efficiently alleviate DN via immune-related pathways. In conclusion, this study provides supportive evidence of the anti-inflammatory effects of GLP supplements, highlighting their potential for promising clinical applications in treating DN.

Objective : To evaluate the vertical distance between the maxillary first molars (MFMs) and the maxillary sinus floor (MSF) and its interrelationship with sex, age, and vertical facial pattern in skeletal ClassⅡ patients to provide a reference for clinical orthodontic treatment. Methods: Sixty teenagers and sixty adults with skeletal Class Ⅱ malocclusion who met the inclusion criteria were selected to evaluate the vertical relationship between the MFMs and the MSF on cone-beam CT (CBCT) images. The vertical distance between the roots of the MFMs and the MSF was measured. Statistical analysis was used to assess differences between patients by sex, age, and vertical facial pattern. Results: The contact percent of the roots of MFMs and MSF was 85% and 56% in skeletal Class Ⅱ teenagers and adults, respectively. The contact percent and penetration percent of the roots with MSF were higher in teenagers than in adults（P<0.05）. The penetration percent of the high-angle (HA) and the normal-angle(NA) groups was 34.1% and 36.6% respectively, which was significantly higher than that in the low-angle (LA) group(20.8%)（P<0.05）. The difference between the distance of the bilateral MFMs and the MSF was not significant in skeletal Class Ⅱ patients (P>0.05); No significant difference was found between different sexes of skeletal Class Ⅱ patients when comparing the distance of the MFMs and the MSF (P>0.05). The MFMs of skeletal Class Ⅱ teenagers were closer to the MSF than those of adults (P<0.05). In the adult group, the distance was not significantly different in different vertical facial patterns (P>0.05). In the teenager group, the MFMs were more closely related to the MSF in the NA and HA groups than in the LA group. Among them, the difference between the mesiobuccal roots and distalbuccal roots was significantly different (P<0.05). There was no significant difference between the groups of the palatal roots (P>0.05). Conclusion The MFMs were closer to the MSF in skeletal Class Ⅱ teenagers than in adults. The distance between the MFMs and MSF was associated with the vertical facial pattern in skeletal Class Ⅱ teenagers, while it was not associated with the vertical facial pattern in adult patients.

ObjectiveTo explore the relationship between the intestinal flora and the impairment of liver and kidney in HIV-infected men who have heterosexual sex with healthy women. MethodsFecal samples from 41 HIV-infected heterosexual men who have sex with women （PMSW） and 43 age- and BMI-matched healthy heterosexual men who have sex with women （NMSW） were collected and subjected to 16S rDNA sequencing. The blood levels of AST， ALT， TBIL， UREA， Cr， UA， β2-MG and other liver and kidney function indicators were measured. Bioinformatics methods were used to analyze the characteristics of the intestinal flora of the patients in these two groups， to compare the differential bacteria strains， and to analyze their correlation with liver and kidney function indicators. ResultsIn comparison with NMSW， the alpha diversity of intestinal flora was decreased in PMSW， and the beta diversity analysis showed significant differences in flora characteristics between the two groups （P<0.05）. The abundance of Clostridium， Phylum thick-walled， Trichosporon， and Clostridium tumefaciens decreased but Fusobacteriota increased （LDA score >4）. The comparison of liver and kidney function indexes revealed that AST， β2-MG levels were higher in PMSW than in NMSW， while TBIL was lower in PMSW than in NMSW. The number of patients with abnormal β2-MG was much higher in PMSW than in NMSW， and the difference was statistically significant （P<0.001）. It was also found that AST was negatively correlated with Clostridium （P<0.05）； TBIL was negatively correlated with Clostridium and positively correlated with Phylum thick-walled and Trichosporon （P<0.05）. β2-MG was negatively correlated with Phylum thick-walled， Clostridium， Trichosporon and Rumenococcus （P<0.05） and positively correlated with Clostridium （P<0.05）. ConclusionIn PMSW group， the alpha diversity of the flora is decreased. AST and β2-MG levels are increased， and TBIL level is decreased. These changes were significantly correlated with different strains of bacteria in the intestinal flora.

BACKGROUND: Exploring the underlying mechanism of rituximab resistance is critical to improve the outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Here, we tried to identify the effects of the axon guidance factor semaphorin-3F (SEMA3F) on rituximab resistance as well as its therapeutic value in DLBCL. METHODS: The effects of SEMA3F on the treatment response to rituximab were investigated by gain- or loss-of-function experiments. The role of the Hippo pathway in SEMA3F-mediated activity was explored. A xenograft mouse model generated by SEMA3F knockdown in cells was used to evaluate rituximab sensitivity and combined therapeutic effects. The prognostic value of SEMA3F and TAZ (WW domain-containing transcription regulator protein 1) was examined in the Gene Expression Omnibus (GEO) database and human DLBCL specimens. RESULTS: We found that loss of SEMA3F was related to a poor prognosis in patients who received rituximab-based immunochemotherapy instead of chemotherapy regimen. Knockdown of SEMA3F significantly repressed the expression of CD20 and reduced the proapoptotic activity and complement-dependent cytotoxicity (CDC) activity induced by rituximab. We further demonstrated that the Hippo pathway was involved in the SEMA3F-mediated regulation of CD20. Knockdown of SEMA3F expression induced the nuclear accumulation of TAZ and inhibited CD20 transcriptional levels via direct binding of the transcription factor TEAD2 and the CD20 promoter. Moreover, in patients with DLBCL, SEMA3F expression was negatively correlated with TAZ, and patients with SEMA3F low TAZ high had a limited benefit from a rituximab-based strategy. Specifically, treatment of DLBCL cells with rituximab and a YAP/TAZ inhibitor showed promising therapeutic effects in vitro and in vivo . CONCLUSION Our study thus defined a previously unknown mechanism of SEMA3F-mediated rituximab resistance through TAZ activation in DLBCL and identified potential therapeutic targets in patients.
Humans ; Animals ; Mice ; Rituximab/therapeutic use* ; Hippo Signaling Pathway ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Prognosis ; Semaphorins/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Membrane Proteins/genetics* ; Nerve Tissue Proteins/genetics*

Objective:To analyze the clinical characteristics of elderly-onset gouty arthritis and risk factors of tophi.Methods:A total of 1 239 gout patients were retrospective selected in the outpatient department of the Gout Clinical Medical Center of the Affiliated Hospital of Qingdao University from 2016 to 2022. According to age of onset, they were divided into the young and middle-aged group(aged<60) consisted of 826 cases, and the elderly group(aged≥60) consisted of 413 cases. Compare the clinical characteristics of elderly with Young and Middle-aged patients.Results:The systolic blood pressure, fasting blood glucose, creatinine, regular exercise, comorbidities, and tophi in the elderly group was higher than that in the middle-aged and young group. The proportion of diastolic blood pressure, serum triglycerides, eGFR, serum uric acid, alcohol consumption rate, and family history of gout was lower than that of young and middle-aged group( P<0.05); In the elderly-onset group, the initial site of arthritis was commonly observed in the first metatarsophalangeal joint. The proportion of the first attack with the upper limb joint was higher in old age group than in young and middle age group( P<0.05). Renal underexcretion type was the main subtype in the elderly group, and the proportion of overproduction type was higher than that of the young and middle-aged group( P<0.05). The logistic regression analysis showed that age, urea nitrogen, disease duration≥10 years and family history of gout were risk factors for tophi in elderly patients( P<0.05). Conclusion:The elderly-onset gout has unique clinical characteristics, characterized by a higher prevalence of tophi, a higher rate of complications. An initial site of arthritis commonly observed in the first metatarsophalangeal joint and the predominant type of uric acid excretion is renal excretion impairment. Early diagnosis and treatment, control of blood uric acid levels, smoking cessation and alcohol, regular exercise should be applied to prevent or delay the formation of tophi.

Objective:To investigate the clinical characteristics and risk factors of multiple tophi among gout patients.Methods:Gout patients treated at Affiliated Hospital of Qingdao University from September 2017 to September 2021 were included retrospectively. According to the number of tophi, the patients were divided into the multiple tophi group, the single tophi group and the non-tophi group. Clinical data were collected, biochemical indices and urine pH value were determined. One- way ANOVA or Chi-square test was used to compare groups, and multivariate logistic regression was used to analyze the risk factors. Results:The age, disease course, blood pressure, serum uric acid, urea nitrogen, and the rate of family history, smoking, drinking, gout attacks≥2 twice per year, hypertension, cardio-cerebrovascular diseases, kidney stones in the multiple tophi group were significantly higher than those in the single tophi group and the non-tophi group. The glomerular filtration rate, urine pH value and the rate of regular exercise were significantly lower than those of single tophi group and non-tophi group. In the multiple tophi group, 245 cases(44.46%) were involved in the interphalangeal joint or metacarpophalangeal joint, 212 cases(38.47%) were involved in other joints of the upper limb, which was second only to the first metatarsophalangeal joint(349 cases, 63.33%). Logistic regression analysis showed that the course of disease, urea nitrogen, serum uric acid, positive family history, drinking, gout attacks ≥twice per year and hypertension were the risk factors for multiple tophi in gout patients. Conclusion:Patients with a long disease course, elevated uric acid, high urea nitrogen, positive family history, alcohol consumption, frequent gout flare and hypertension are more likely to develop multiple tophi.

Objective:To establish a xenograft model of cutaneous squamous cell carcinoma (CSCC) in nude mice, and to explore mechanisms underlying synergistic induction and promotion of CSCC in nude mice by ultraviolet radiation and human papillomavirus (HPV) infection.Methods:The human CSCC A431 cells were divided into 3 groups, namely HPV16 E6 overexpression group (LV-OE-HPV16 E6 group) transfected with adenovirus-mediated HPV16 E6 gene, empty vector group transfected with empty adenovirus vectors, and blank control group remaining untransfected. Using serum-free Dulbecco′s modified Eagle′s medium (DMEM) , A431 cells in the empty vector group and LV-OE-HPV16 E6 group were prepared into single-cell suspensions, which were subcutaneously inoculated into the left buttocks of SKH-1 nude mice separately, namely empty vector group ( n = 16) and LV-OE-HPV16 E6 group ( n = 16) . Tumor growth was observed and recorded for the mice every 3 days. When the tumor size reached 150 mm 3, the modeling was considered successful. After successful modeling, 8 mice in each group were irradiated with ultraviolet light at a dose of 1 440 mJ·cm -2·d -1 for 12 minutes each time, the other 8 mice in each group received no ultraviolet radiation, that is to say, all the 32 mice were divided into 4 groups: empty vector group, empty vector + UV group, LV-OE-HPV16 E6 group, and LV-OE-HPV16 E6 + UV group. After 4-week radiation, these nude mice were sacrificed, tumor weight and volume were measured, a tumor growth curve was drawn, immunohistochemistry study, Western blot analysis and real-time fluorescence-based quantitative PCR (qRT-PCR) were conducted to determine the protein and mRNA expression of Wnt1 and β-catenin in CSCC tissues collected from nude mice, respectively. For normally distributed measurement data, analysis of variance was used for intergroup comparisons, and least significant difference- t test for multiple comparisons; for non-normally distributed measurement data, rank sum test was used for intergroup comparisons. Results:Compared with the empty vector group (2.20 ± 0.24 g) , the tumor weight significantly increased in the empty vector + UV group (2.90 ± 0.36 g, t = 4.39, P < 0.001) , LV-OE-HPV16 E6 group (3.19 ± 0.32 g, t = 6.77, P < 0.001) , and LV-OE-HPV16 E6 + UV group (4.41 ± 0.18 g, t = 20.11, P < 0.001) ; the tumor volume was also significantly higher in the empty vector + UV group (1 033.12 ± 400.15 mm 3, t = 1.90, P < 0.001) , LV-OE-HPV16 E6 group (1 119.21 ± 447.57 mm 3, t = 2.21, P < 0.001) , and LV-OE-HPV16 E6 + UV group (1 464.29 ± 409.98 mm 3, t = 4.22, P < 0.001) than in the empty vector group (688.94 ± 319.31 mm 3) . Immunohistochemical study showed no significant difference in the protein expression of Wnt1 and β-catenin among the 4 groups ( F = 0.76, 0.71, respectively, both P > 0.05) ; Western blot analysis showed significant differences in the protein expression levels of Wnt1 and β-catenin among the 4 groups ( F = 16.74, 49.90, respectively, both P < 0.05) , which were significantly higher in the LV-OE-HPV16 E6 + UV group than in the empty vector group, empty vector + UV group and LV-OE-HPV16 E6 group (all P < 0.05) . qRT-PCR showed a significant difference in the mRNA expression of Wnt1 and β-catenin among the 4 groups ( F = 7.77, 8.38, respectively, both P<0.05) , and the LV-OE-HPV16 E6 + UV group showed significantly increased Wnt1 mRNA expression levels compared with the empty vector group, empty vector + UV group and LV-OE-HPV16 E6 group (all P < 0.05) . Conclusion:Ultraviolet radiation and HPV infection showed synergistic effect on the induction and promotion of CSCC.

Objective:To analyze the influencing factors of gout patients and explore whether there is an interaction between serum uric acid and diastolic blood pressure affecting the onset of tophi.Methods:A total of 4 798 gout patients were retrospective selected in the outpatient Department of the Gout Clinical Medical Center of the Affiliated Hospital of Qingdao University from September 2016 to May 2020. It was divided into tophi group and non-tophi group to compare the differences in indicators. A logistic regression model was used to analyze the influencing factors of tophi, and an interaction model was constructed to analyze the interactions.Results:Multivariate logistic regression analysis showed significant associations between age, diastolic blood pressure, alcohol consumption history, gout family history, blood uric acid, urea nitrogen, and creatinine clearance and tophi formation. The results of blood uric acid-related interaction analysis showed a significant interaction between blood uric acid and diastolic blood pressure( Pinteraction=0.014), and the risk of developing tophi in low diastolic blood pressure and high diastolic blood pressure group increased by 34.4%( OR=1.344, 95% CI 1.105-1.635, P=0.003) and 95.4%( OR=1.954, 95% CI 1.558-2.450, P<0.001) in the high blood uric acid group compared with the low blood uric acid group. The results of diastolic blood pressure and blood uric acid subgroup analysis showed that there was no statistical difference in the risk of developing tophi in people with low uric acid levels( P=0.238), but in people with high uric acid levels, the risk of developing tophi was 67%( OR=1.670, 95% CI 1.379-2.022, P<0.001) higher than that in the low uric acid group. Conclusion:Age, diastolic blood pressure, combined alcohol consumption history and gout family history, blood uric acid, renal function are related to the occurrence of tophi. High uric acid and high diastolic blood pressure have interaction on the occurrence of tophi. Attention and proactive intervention shall be applied to this group of patients.