Objective To explore the polymorphism of tyrosinase (TYR) and melanocortin 1 receptor (MC1R) genes and their mRNA expression levels in relation to coat-color phenotypes in guinea pigs, providing genetic markers for locating dominant traits in guinea pigs. Methods A total of 57 self-bred ordinary-level guinea pigs were selected and divided into three groups based on coat color: white (n=22), variegated (n=22) and black (n=13). The guinea pigs were euthanized with an overdose of pentobarbital sodium via intraperitoneal injection. DNA was then extracted from the dorsal skin tissue. Polymorphism in the coding sequence (CDS) of the exons of the TYR and MC1R genes in each group was detected by cloning and sequencing. The mRNA expression of the two genes in skin tissues was detected by real-time fluorescent quantitative PCR to investigate the relationship between these genes and guinea pig coat color. Results A single nucleotide polymorphism (SNP) site was found in the CDS region of TYR exon Ⅰ, where the base A was replaced by G. All white guinea pigs had the G/G genotype for TYR, while no deep-colored (variegated and black) guinea pigs exhibited the G/G genotype for TYR. Most deep-colored guinea pigs had the A/A genotype, and a few had A/G genotype. The A/A genotype frequency in black guinea pigs was higher than in variegated guinea pigs. A 2 760 bp sequence deletion was identified in the exon of the MC1R gene, marked as the - gene, with non-deleted samples marked as N gene. Most white guinea pigs had the -/- genotype for MC1R, variegated guinea pigs mainly had the -/N genotype, and black guinea pigs mainly had the N/N genotype, with a few showing the -/N. The TYR gene expression level was higher in white guinea pigs, lower in variegated guinea pigs, and intermediate in black guinea pigs, but there was no significant difference among the three groups (P>0.05). The MC1R gene expression level in white guinea pigs was extremely low, while both variegated and black guinea pigs showed significantly higher levels than white guinea pigs (P<0.01). Black guinea pigs showed significantly higher levels than variegated guinea pigs (P<0.05). ConclusionThe TYR and MC1R genes synergistically regulate coat color of guinea pigs. The G-site mutation in the TYR gene may lead to albinism, and the change of N-site in the MC1R gene affects the depth of the coat color.

Objective To investigate the epidemiological characteristics of dengue fever in Shenzhen City in 2024, so as to provide insights into formulation of the preventive and control measures for dengue fever. Methods The epidemiological data of dengue cases reported in Shenzhen City in 2024 were extracted from the China Disease Prevention and Control Information System and field epidemiological survey data of dengue fever in Shenzhen City, and the temporal, regional and population distributions of dengue fever cases, source of acquire dengue virus infections, disease diagnosis and treatment and outbreaks were analyzed. The dengue virus nucleic acid was tested and the serotypes of dengue virus were characterized using real-time quantitative reverse transcription PCR (RT-qPCR) assay, and the dengue virus gene was sequenced using next-generation sequencing (NGS). In addition, the surveillance on the density of Aedes albopictus was performed using Breteau index (BI) and mosquito oviposition index (MOI). Results A total of 1 735 dengue fever cases were reported in Shenzhen City in 2024, including 952 local cases and 783 imported cases. Most imported dengue fever cases acquired infections from eight cities of Foshan, Guangzhou, Zhongshan, Jiangmen, Dongguan, Zhaoqing, Huizhou, and Zhuhai in the Pearl River Delta region (664 cases, 84.8% of total imported cases) into Baoan, Longgang, and Nanshan districts. The epidemic exhibited an early onset and rapid progression, peaking during the period between September and November (1 632 cases, 94.1% of total cases), and dengue fever cases were distributed across 73 subdistricts in 10 districts, with most cases reported in densely populated central and western regions. The dengue fever cases had a male-to-female ratio of 1.9∶1.0, and a median age of 37 (21) years, with a higher median age among local cases than among imported cases [40 (20) years vs. 33(15) years; Z = -10.30, P < 0.05]. Housework, unemployment, workers, and business service were predominant occupations (1 405 cases, 81.0% of total cases), and there was a significant difference in the constituent ratio of occupations between local and imported cases (χ² = 92.30, P < 0.05). Among the 1 735 dengue fever cases, the median duration from onset to definitive diagnosis was 3.3 (2.9) days, and 1 686 cases (97.2%) were identified in healthcare facilities, with a low rate of hospitalization and isolation seen in 1 701 inpatients with available epidemiological data (485 cases, 28.5% of total inpatients). A total of 29 outbreaks of dengue fever occurred in Shenzhen City across 2024, which primarily in construction sites (27 outbreaks, 93.1% of total). Dengue virus type I was the dominant serotype causing dengue fever in Shenzhen City in 2024. Sequencing showed that the genomes of dengue virus from multiple dengue fever cases in Shenzhen City shared a high sequence homology with those from cities neighboring Shenzhen City, and there might be intra-city transmission of dengue virus among multiple construction sites in Shenzhen City. The Aedes albopictus density was significantly higher in Shenzhen City in 2024 than in 2023, peaking from May to September. The annual MOI values ranged from 0.9 to 14.0, and the BI values ranged from 0.6 to 6.0. Conclusions The overall epidemic of dengue fever was severe in Shenzhen City in 2024, which was greatly affected by case importation from neighboring cities, construction sites-centered local transmission, and the effectives of routine mosquito vector control was not satisfactory. Integrated dengue fever control measures should be implemented, focusing on regional joint prevention and control mechanisms, capacity building for mosquito vector control, addressing challenges in epidemic containment at construction sites, and strengthening case detection and management systems.

Melatonin (Mel) has been shown to have cardioprotective effects, but its action on ion channels is unclear. In this experiment, we investigated the inhibitory effect of Mel on late sodium currents (I_Na.L) in mouse ventricular myocytes and the anti-arrhythmic effect at the organ level as well as its mechanism. The whole-cell patch clamp technique was applied to record the ionic currents and action potential (AP) in mouse ventricular myocytes while the electrocardiogram (ECG) and monophasic action potential (MAP) were recorded simultaneously in mouse hearts using a multichannel acquisition and analysis system. The results demonstrated that the half maximal inhibitory concentration (IC₅₀) values of Mel on transient sodium current (I_Na.T) and specific I_Na.L opener 2 nmol·L^-1 sea anemone toxins II (ATX II) increased I_Na.L were 686.615 and 7.37 μmol·L^-1, respectively. Mel did not affect L-type calcium current (I_Ca.L), transient outward current (I_to), and AP. In addition, 16 μmol·L^-1 Mel shortened ATX II-prolonged action potential duration (APD), suppressed ATX II-induced early afterdepolarizations (EADs), and significantly reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused mouse hearts. In conclusion, Mel exerted its antiarrhythmic effects principally by blocking I_Na.L, thus providing a significant theoretical basis for new clinical applications of Mel. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Wuhan University of Science and Technology (2023130).

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To observe the clinical efficacy and safety of spironolactone combined with sacubitril/valsartan in the treatment of patients with hypertensive nephropathy.Methods The patients with hypertensive nephropathy were randomly divided into control group and treatment group.The control group was treated with sacubitril/valsartan(100-200 mg·d-1 in the morning),and treatment group was combined with low-dose spironolactone treatment(20 mg·d-1 in the morning)on the basis of control group.Both groups were treated continuously for 12 weeks.The clinical efficacy was compared;the blood pressure,urinary microalbumin(mAlb),urinary β2 microglobulin(β2-MG)and serum cystatin C(Cys-C),transforming growth factor-β1(TGF-β1),connective tissue growth factor(CTGF)and angiotensin Ⅱ(Ang Ⅱ)and adverse drug reactions were observed before and after treatment.Results There were 87 cases in treatment group and 86 cases in control group were included respectively.After treatment,the total effective rates in treatment group and control group were 95.40％(83 cases/87 cases)and 82.56％(71 cases/86 cases),with significant difference(P＜0.05).After treatment,the systolic blood pressure values in treatment group and control group were(124.65±9.65)and(130.27±8.93)mmHg,the diastolic blood pressure values were(75.08±7.14)and(80.45±7.35)mmHg,urinary mAlb levels were(42.58±5.65)and(51.28±6.64)mg·L-1,urinary β2-MG levels were(0.46±0.17)and(0.75±0.25)mg·L-1,24 h urinary protein quantitation levels were(138.49±46.64)and(216.48±65.27)mg,serum Cys-C levels were(0.63±0.26)and(0.85±0.24)mg·L-1,TGF-β1 levels were(98.67±21.43)and(112.46±26.72)pg·mL-1,CTGF levels were(1 206.54±236.56)and(1 340.51±248.25)pg·mL-1,Ang Ⅱ levels were(101.55±17.62)and(115.65±20.08)pg·mL-1,all with significant difference(all P＜0.05).The incidence of adverse drug reactions in treatment group and control group were 6.90％(6 cases/87 cases)and 2.33％(2 cases/86 cases),with no significant difference(P＞0.05).Conclusion Compared with sacubitril/valsartan alone,spironolactone combined with sacubitril/valsartan can better reduce blood pressure,improve renal function and delay progression of renal fibrosis in the treatment of hypertensive nephropathy,and has definite efficacy,with good safety.

Objective:To explore the microbiological and disease distribution characteristics of multidrug-resistant bacteria in patients hospitalized in a critical care rehabilitation ward, and to analyze the risk factors leading to multidrug-resistant bacterial infections.Methods:Microbiology screening data describing 679 patients admitted to a critical care rehabilitation ward were retrospectively analyzed to divide the subjects into a multidrug-resistant group (positive for multidrug-resistant bacterial infections, n=166) and a non-multidrug-resistant group (negative for multidrug-resistant bacterial infections, n=513). The risk factors were then analyzed using logistic regression. Results:Among 369 strains of multidrug-resistant bacteria observed, 329 were gram-negative bacteria (89.2%), mainly Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli. They were distributed in sputum (56.9%) and mid-epidemic urine (28.2%) specimens. Patients whose primary disease was hemorrhagic or ischemic cerebrovascular disease accounted for 40.96% and 23.49% of the multidrug-resistant bacterial infections, respectively. Logistic regression analysis showed that albumin level, dependence on mechanical ventilation, central venous cannulation, or an indwelling urinary catheter or cystostomy tube were significant independent predictors of such infections.Conclusion:The multidrug-resistant bacterial infections of patients admitted to the critically ill rehabilitation unit are mainly caused by gram-negative bacteria. Their occurrence is closely related to low albumin levels and mechanical ventilation, as well as to bearing an indwelling central venous catheter, a urinary catheter or a cystostomy catheter.

italic>Astragalus polysaccharides are the most immunoregulatory active and abundant substances in Astragalus, with anti-tumor, anti-viral, and immune-promoting biological activities. They have been widely used in clinical practice. Previous studies have found that Astragalus polysaccharides are mainly composed of two different polysaccharides, APS-I (>2 000 kDa) and APS-Ⅱ (10 kDa), with APS-Ⅱ (10 kDa) being the most active component of Astragalus polysaccharides. We used α-1,4-glucan endo-hydrolysis enzyme to degrade APS-Ⅱ into oligosaccharides, and screened the immune activity of oligosaccharides in vitro. We found that the overall immune activity of 2-9 oligosaccharides was low, while the immune activity of 10-14 oligosaccharides was strong, and the activity was better than that of untreated APS-Ⅱ. To investigate the key structural features of APS-Ⅱ oligosaccharides that play a role in immune activity, we used MALDI-TOF-MS biochemical mass spectrometry and high-resolution mass spectrometry instrument ESI-Q Exactive-MS to analyze the APS enzymatic oligosaccharides. By comparing, we found that 10-14 oligosaccharides contain 1→4 and 1→6 branched structures with coexisting linkages, suggesting that 1→4 and 1→6 linkages in branched structures are key structural features that play a role in the immune activity of APS-Ⅱ, laying a theoretical foundation for the structure-activity relationship of Astragalus polysaccharides and oligosaccharides.

ObjectiveTo analyze the long-term trends of the disease burden of diabetes attributed to metabolic factors in China from 1990 to 2019, and provide scientific recommendations for diabetes prevention and control in China. MethodsDescriptive analysis was conducted on the disease burden data of diabetes attributed to metabolic factors in China from 1990 to 2019, obtained from GBD 2019, encompassing death form diabetes, disability-adjusted life years (DALY), years of life lost (YLL), and years lived with disability (YLD). Joinpoint regression models were employed to analyze the long-term trends in mortality and DALY rates. Furthermore, the study examined the impact of two metabolic risk factors, high fasting plasma glucose (FPG) levels and high body mass index (BMI) levels, on the disease burden of diabetes. ResultsFrom 1990 to 2019, the overall standardized mortality and DALY rates attributed to metabolic factors for diabetes in the general population in China showed an upward trend, with both average annual percent changes (AAPCs) of 0.1% in the total population. The trend was upward in males with AAPCs of 0.9% and 0.6%, while it was downward in females with AAPCs of -0.4% and -0.3%. As age increased, the disease burden of diabetes attributed to metabolic factors showed an upward trend, with high FPG and high BMI ranking as the top two attributing risk factors. The disease burden of diabetes attributed to metabolic factors was higher in Chinese males than females. ConclusionThe disease burden of diabetes attributed to metabolic factors is increasing among the overall population and particularly among males, while the burden for female is declining. There is a need to increase intervention efforts for males aged 65 and above, provide scientific guidance on residents’ diet and lifestyle habits, and control blood glucose and body weight.

Objective To explore the construction and visualization for knowledge graph of Ling Shu(Spiritual Pivot),with a view to providing ideas for the structured storage and display of the theoretical knowledge of the ancient Chinese medical books.Methods Using the professional idea of constructing knowledge graphs for reference,text mining technology was applied to construct the thesaurus,and then word division,entity recognition,and relationship extraction for the original text of Ling Shu were performed to get the elements of knowledge graph construction.The graph database Neo4j was used for the storage and query of the knowledge graph,and then the visual display of the knowledge graph was achieved.Results The 1 216 high-quality words consisting of the thesaurus of Ling Shu were obtained,and the construction of the knowledge graph of the theory of Ling Shu was realized.The constructed knowledge graph basically displayed the traditional Chinese medicine theories such as the correlation of visceral manifestations with essence qi,and the relationship between emotions and the five-zang organs described in Ling Shu,which made the retrieval and utilization of the related entities and relationships possible,and provided ideas for the structured storage and display of the theoretical knowledge of the ancient books of Chinese medicine.Conclusion The knowledge graph construction technology can be used to obtain the Chinese medicine theoretical knowledge graph of Ling Shu,and to display the knowledge connections of yin-yang and the five elements,and the internal organs and meridians expressed in the Ling Shu.The construction of the knowledge graph and its storage in the graph database enable the knowledge graph involved in the text of Ling Shu to be displayed in the form of visualized semantic network graph,and also make the embedding of other search systems such as the semantic search and semantic wiki possible,which will be helpful for the development of Chinese medicine intelligent medical services.

Objective To explore the relevant factors of new-onset conduction disturbance(NOCD)after transcatheter aortic valve replacement(TAVR),such as anatomical structure,device type,surgical strategies,etc.,discover relevant predictive factors,and establish a predictive model to assess the risk of conduction blockages.Methods From January 2016 to March 2022,clinical data of symptomatic patients with severe aortic valve stenosis or severe regurgitation who underwent TAVR at Xiangya Second Hospital of Central South University were collected through the hospital information system and imaging database.ECG,echocardiography,CTA,surgical materials,etc.,were extracted and analyzed by specialists.SPSS software was used for statistical analysis,and a multi-factor regression prediction model for NOCDwas built.Results A total of 184 patients were included,the occurrence rate of NOCD after TAVR was 31.0%,pure regurgitation patients'NOCD occurrence rate was 63.6%(7/11).The NOCD group had a larger aortic angles[(57.7±10.3)°vs.(52.0±9.0)°,P＜0.001],larger Oversizing[(129±28)%vs.(120±21)%,P=0.018],deeper implantation depth[(7.2±5.1)mm vs.(4.8±4.2)mm,P=0.001],and higher pure regurgitation patients'proportion[12.3%vs.3.1%,P=0.037]than the non-NOCD group.Multifactorial Logistic regression analysis indicated that an aorta angle＞54.5°(OR 3.78,95%CI 1.86-7.63,P＜0.001)or implantation depth＞5.7 mm(OR 3.39,95%CI 1.68-6.85,P＜0.001)are independent risk factors for new onset conduction disturbances after TAVR,and a predictive model was established with aortic angle,implantation depth,and Oversizing ratio as variables.The receiver operating characteristics curve showed area under ROC curve 0.709,95%CI 0.623-0.795,predicting NOCD after TAVR.Conclusions A retrospective analysis carried out at a single center discovered that the aortic angle in the NOCD group was larger than that in the non-NOCD group,the Oversizing ratio was higher,the implantation location was deeper,and there was a higher proportion of patients with pure regurgitation lesions.An aortic angle greater than 54.5°or an implantation depth more than 5.7 mm were identified as independent risk factors for NOCD after TAVR.