With the application and popularization of the polymerase chain reaction, many ocular diseases with unknown etiology in the past have been confirmed to be related to viral infections; from the classic herpes simplex keratitis to the cytomegalovirus intraocular infection which is gradually recognized by people at present, various viral ocular diseases have received increasing clinical attention. Ocular viral infections are complicated with various types of viruses causing different clinical manifestations. Since it is difficult to obtain corresponding tissue specimens from patients with viral ocular diseases, establishing an effective animal model is a crucial foundation for studying the characteristics of the disease course, the pathogenesis, and the pre-clinical evaluation of drugs. Based on the literature on animal models related to viral ocular diseases in recent years, this paper comprehensively summarizes the animal models of various diseases from the anterior segment to the posterior segment of the eye caused by different viruses and introduces in detail the types of viruses, viral loads, and the methods of virus challenge on various models; besides, it conducts a comparative evaluation from multiple dimensions such as the model stability, advantages and disadvantages of the models, and their application situations, so as to provide a basis for subsequent basic research on related diseases and drug transformation.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

OBJECTIVE: This study aimed to investigate the impact of glycemic control and diabetes duration on subsequent myocardial infarction (MI) in patients with both coronary heart disease (CHD) and type 2 diabetes (T2D). METHODS: We conducted a retrospective cohort study of 33,238 patients with both CHD and T2D in Shenzhen, China. Patients were categorized into 6 groups based on baseline fasting plasma glucose (FPG) levels and diabetes duration (from the date of diabetes diagnosis to the baseline date) to examine their combined effects on subsequent MI. Cox proportional hazards regression models were used, with further stratification by age, sex, and comorbidities to assess potential interactions. RESULTS: Over a median follow-up of 2.4 years, 2,110 patients experienced MI. Compared to those with optimal glycemic control (FPG < 6.1 mmol/L) and shorter diabetes duration (< 10 years), the fully-adjusted hazard ratio ( HR) (95% Confidence Interval [95% CI]) for those with a diabetes duration of ≥ 10 years and FPG > 8.0 mmol/L was 1.93 (95% CI: 1.59, 2.36). The combined effects of FPG and diabetes duration on MI were largely similar across different age, sex, and comorbidity groups, although the excess risk of MI associated with long-term diabetes appeared to be more pronounced among those with atrial fibrillation. CONCLUSION Our study indicates that glycemic control and diabetes duration significant influence the subsequent occurrence of MI in patients with both CHD and T2D. Tailored management strategies emphasizing strict glycemic control may be particularly beneficial for patients with longer diabetes duration and atrial fibrillation.
Humans ; Diabetes Mellitus, Type 2/blood* ; Male ; Female ; Middle Aged ; Aged ; Coronary Disease/complications* ; Myocardial Infarction/etiology* ; Retrospective Studies ; China/epidemiology* ; Glycemic Control ; Blood Glucose ; Adult ; Risk Factors ; Time Factors

Objective To investigate the protective effect of liraglutide against myocardial ischemia-reperfusion injury(MIRI)in rats and its relationship with pyroptosis.Methods Forty SPF-grade male SD rats were randomly divided into five groups:the sham operation group(Sham group),the MIRI model group(I/R group),the pyroptosis inhibitor group(Dis+I/R group),the liraglutide group(Lir+I/R group),and li-raglutide+pyroptosis inhibitor group(Lir+Dis+I/R group),with 8 rats in each group.Except for the Sham group,MIRI models were established in all other groups,followed by corresponding treatments.Myocardial infarct size was measured by 2,3,5-triphenyltetrazolium chloride(TTC)staining.Superoxide dismutase(SOD)activity and malondialdehyde(MDA)level were detected using assay kits.Serum levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)and IL-1β were measured by ELISA.Protein expression of apoptosis-associated speck-like protein containing a CARD(ASC),caspase-1,and cleaved N-ter-minal gasdermin D(GSDMD-N)was detected by Western blot.Results Compared with the I/R group,myo-cardial infarct size was reduced in the Lir+I/R and Dis+I/R groups(P＜0.05),with a further reduction in the Lir+Dis+I/R group compared to the Lir+I/R group(P＜0.05).SOD activity increased and MDA levels decreased in the Lir+I/R and Dis+I/R groups compared to the I/R group(P＜0.05),while SOD activity was further elevated in the Lir+Dis+I/R group compared to the Dis+I/R group and Lir+I/R group(P＜0.05).NLRP3 and IL-1β protein expression levels were reduced in the Lir+I/R and Dis+I/R groups compare to the I/R group(P＜0.05),and IL-1β expression level was further reduced in the Lir+Dis+I/R group com-pared to the Dis+I/R group and Lir+I/R group(P＜0.05).The protein expression levels of ASC and GSD-MD-N in the Lir+I/R group were lower than those in the I/R group(P＜0.05);the protein expression levels of ASC,caspase-1 and GSDMD-N in the Dis+I/R group were lower than those in the I/R group(P＜0.05).ASC expression level further reduced in the Lir+Dis+I/R group compared to both the Dis+I/R and Lir+I/R groups(P＜0.05).Conclusion Liraglutide exerts a protective effect in MIRI,potentially by inhibi-ting pyroptosis.

Objective To investigate the expression of serum microRNA-204-5p(miR-204-5p)in patients with sudden deafness(SD)and its relationship with cochlear function and hearing prognosis.Methods A to-tal of 113 SD patients admitted to this hospital from October 2020 to October 2023 were selected as the case group.According to the hearing prognosis of SD patients,they were divided into a poor prognosis group(n=43)and a good prognosis group(n=70).Another 95 healthy people who underwent the physical examination were selected as the control group.Real-time fluorescent quantitative PCR and enzyme-linked immunosorbent assay were used to detect serum levels of miR-204-5p and endothelin-1(ET-1),and the relationship between them and cochlear function was analyzed.Automatic hemorheology instrument was used to detect the hemo-dynamic parameters.Multivariate Logistic regression was used to analyze the influencing factors of hearing prognosis in SD patients.Receiver operating characteristic(ROC)curve was used to analyze the predictive val-ue of serum miR-204-5p in hearing prognosis of SD patients.Results The serum levels of miR-204-5p and ET-1 and hemodynamic parameters including plasma viscosity(PV),low-shear viscosity(LSV)and whole blood high-shear viscosity(HSV)in the case group were significantly higher than those in the control group(P<0.05).The incidence of cochlear dysfunction in the miR-204-5p high expression group was higher than that in the miR-204-5p low expression group(P<0.05).The levels of serum miR-204-5p,ET-1,PTA,HSV,LSV and PV in the poor prognosis group were significantly higher than those in the good prognosis group(P<0.05).HSV,LSV,PV,miR-204-5p and ET-1 were related factors affecting the hearing prognosis of SD patients(P<0.05).The area under the curve of serum miR-204-5p,ET-1 combined with hemodynamic pa-rameters to predict the hearing prognosis of SD patients was 0.976.It was better than that of each individual diagnosis(Zfive combination-HSV=3.464,Zfive combination-LSV=3.014,Zfive combination-PV=3.741,Zfive combination-miR-204-5p=3.476,Zfive combination-ET-1=2.829,P=0.001,0.003,<0.001,0.001,0.005).The sensitivity and specificity of combined prediction were 95.35%and 88.57%,respectively.Conclusion Serum miR-204-5p level is significantly in-creased in SD patients,which is closely related to cochlear function and hearing prognosis.Serum miR-204-5p and ET-1 levels combined with hemodynamic indicators have higher predictive efficiency for hearing prognosis in SD patients.

italic>Platycodon grandiflorum (Jacq.) A. DC is one of the most commonly used bulk medicinal herbs. It has important value in the fields of medicine, food and cosmetics, and its market demand is increasing year by year, and it has a good development prospect. In this study, based on 403 distribution records and 8 environmental variables, we used Maxent model to predict the potential distribution of P. grandiflorum under climate change. The results showed that the model simulation effect was the best when the Maxent parameter was FC (feature combination) = LQPH (L: linear features; Q: quadratic features; P: product features; H: hinge features) and RM (regularization multiplier) = 2.1, AUC (area under curve) = 0.901, and the model prediction showed that P. grandiflorum was widely distributed in 28 provinces of China under the current climate conditions, with a suitable area of 2 337 419.98 km². Under the influence of climate change in the future, the area of suitable habitat of P. grandiflorum showed a decreasing trend, and the distribution center as a whole showed a trend of northward and eastward shift. The distribution area of P. grandiflorum in the three main producing areas is affected by climate change, and the overall trend is that the future suitable distribution area of Chifeng in Inner Mongolia increases, while the future suitable distribution area of Zibo in Shandong and Taihe, Bozhou in Anhui decreases or even disappears under the SSP5-8.5 scenario (shared socioeconomic pathways). It is suggested to maintain and protect the ecological environment and germplasm resources of the reserved area suitable for the growth of P. grandiflorum, and increase the cultivation research in the expansion area of P. grandiflorum, so as to lay a foundation for the subsequent expansion of P. grandiflorum planting and to promote the protection and sustainable development of P. grandiflorum resources.

Objective:To investigate the influencing factors for total number, total volume, and total iron burden of cerebral microbleeds (CMBs) and the relationship between CMBs with cognitive impairment in end-stage renal disease (ESRD) using semi-automatic quantitative susceptibility mapping (QSM).Methods:The study was a cross-sectional study. Clinical and imaging data of 46 ESRD patients with≥1 CMBs who attended Tianjin First Central Hospital from November 2018 to August 2022 were retrospectively analyzed. There were 26 males and 20 females, aged 42-75 years. All patients underwent susceptibility-weighted imaging (SWI) scanning, then SWI data was post-processed to obtain QSM. The semi-automatic dynamic programming algorithm was used to get the volume and mean susceptibility value of each CMB by sketching the boundary of CMBs. The CMBs iron load total volume were calculated. Stepwise linear regression analysis was used to explore independent influencing factors for the number, total volume, and total iron burden of CMBs in ESRD patients. Partial correlation analysis was used to explore the relationship between CMBs and cognitive impairment with the other signs of cerebral small vessel diseases as covariates.Results:In patients with ESRD, CMBs were located in the frontal lobe in 19 cases, parietal lobe in 9 cases, temporal lobe in 19 cases, occipital lobe in 14 cases, basal ganglia in 27 cases, dorsal thalamus in 15 cases, centrum semiovale in 14 cases, cerebellum in 14 cases, and brainstem in 13 cases. C-reactive protein levels (95% CI 101.81-157.85, r=0.96, P=0.001) and creatinine levels (95% CI 5.32-29.61, r=0.71, P=0.010) were influencing factors for the total iron burden of CMBs. C-reactive protein levels (95% CI 0.72-1.15, r=0.99, P=0.001) and creatinine levels (95% CI 0.03-0.22, r=0.89, P=0.014) were influencing factors for the total volume of CMBs. C-reactive protein levels (95% CI 0.10-0.12, r=0.96, P=0.001) and alkaline phosphatase levels (95% CI 0.16-0.38, r=0.59, P=0.001) were influencing factors for the number of CMBs. The total volume ( r=-0.61, P=0.009) and total iron burden ( r=-0.71, P=0.002) of CMBs in the frontal lobe were negatively correlated with cognitive function. However, although the number of CMBs in the frontal lobe was negatively correlated with cognitive function, the statistics analysis was insignificant ( r=-0.53, P=0.063). Conclusions:C-reactive protein and creatinine are influencing factors for CMBs′ total volume and total iron burden; C-reactive protein levels and alkaline phosphatase are influencing factors for the number of CMBs. The total iron burden and total volume of CMBs in the frontal lobe may be the biomarkers of cognitive impairment in patients with end-stage renal disease.

Objective:This study aims to evaluate the clinical efficacy and safety of Dibai Yijing Formula(DYF)in the treat-ment of male infertility with essence deficiency in the kidney and damp-heat in the essence chamber(Abbreviation:kidney deficiency and damp-heat type).Methods:This study employed a randomized,controlled clinical trial design,recruiting 72 male patients with infertility due to kidney deficiency and damp-heat type.Patients were randomly assigned to an treatment group(36 patients)and a control group(36 patients)using a random number table.The control group received oral Clomiphene Citrate Capsules(50 mg,twice daily),while the treatment group received oral DYF(one dose daily,200 ml each time,30 minutes after breakfast and dinner).Both groups underwent a 12-week treatment period.After treatment,sperm concentration(SC),percentage of progressively motile sperms(PR),total sperm motility[PR+percentage of non-progressively motile sperms(NP)],and semen volume(SV)were compared between the two groups before and after treatment.Additionally,the total score of Traditional Chinese Medicine(TCM)syndrome score and sperm DNA fragmentation index(DFI)and pregnancy outcomes of the patients'spouses were compared between the two groups.Results:Three patients dropped out from the treatment group and four from the control group.There were no statistically sig-nificant differences in semen parameters between the two groups(P＞0.05).After treatment,the patients in the treatment group showed significant difference in the percentage of SC([19.42±5.30]x 106/ml vs[10.75±2.41]x 106/ml),PR([27.72±6.62]％vs[20.04±4.10]％),PR+NP([49.86±10.68]％vs(33.74±5.58)％],DFI([12.33±3.43]％vs[15.06±3.98]％)and TCM symtom score([7.45±1.82]vs[13.85±1.91]),and the difference was statistically significant(P＜0.05).The patients in the control group showed significant difference in the percentage of SC([19.56±5.24]× 106/ml vs[11.31±2.08]× 106/ml)and TCM symptom score([12.81±1.86]vs[14.06±1.64]).But no significant changes were observed in the PR([21.75±5.93]％vs[20.05±4.67]％),PR+NP([34.23±7.15]％vs[32.35±4.09]％),SV([3.19±1.08]ml vs[3.12±1.13]ml),and DFI([15.11±4.76]％vs[15.51±4.35]％)were not statistically significant(P＞0.05).Improve-ments in PR,PR+NP,TCM symptom score and DFI in the treatment group were better than those in the control group after treatment(P＜0.05);the differences in SC and SV and spousal pregnancy in the treatment group were not statistically significant compared with those in the control group(P＞0.05).No serious adverse events occurred in both groups during the treatment period.Conclusion:The treatment of male infertility with DYF is effective and safe.

Objective:To explore the clinical features, treatment and prognosis of patients with pneumatosis cystoides intestinalis (PCI).Methods:The clinical data of 25 PCI patients at Peking University People's Hospital admitted from Jan 2011 to Dec 2020 were retrospectively analyzed .Results:Among these 25 PCI patients, there were 9 males and 16 females with a median age of 69 (55-78) years. Six patients were asymptomatic, while the main complaint of the remaining patients was abdominal pain (12 cases), followed by diarrhea (4 cases), constipation (2 cases), and abdominal distension (1 case). Fifteen patients with PCI also had hypoalbuminemia. The main radiological manifestation of PCI was the presence of multiple gas-filled cysts within the intestinal wall, with 23 cases occurring in the colon and 17 cases combined with free intra-abdominal gas. All patients were cured with conservative treatment, with no PCI-related deaths during follow-up .Conclusions:PCI is a rare gastrointestinal disease with atypical clinical manifestations. Conservative management is an effective treatment with good prognosis.

By using thioflavin T(ThT)as displacement-based fluorescent probes,three kinds of aptasensors were constructed for rapid detection of three kinds of small molecules such as ochratoxin A(OTA),aflatoxin B1(AFB1)and adenosine.In the absence of target molecule,ThT bound with the aptamer to form an aptamer-ThT complex and exhibited a significant fluorescence response.Upon the addition of target molecule,because of the higher affinity between target and aptamer than that between ThT and the aptamer,ThT was displaced by the target molecule from the aptamer-ThT complex,resulting in weakened fluorescence signal.Based on this principle,the target molecule could be detected quantitatively.Further study through circular dichroism spectra showed that there was no significant change in the conformation of the aptamer after addition of ThT or target molecules.The stoichiometric ratios of ThT to OTAapt,AFB1apt and Adeapt measured through the method of equimolar continuous variation was 1∶1,1∶1 and 2∶1,respectively,and their dissociation constants were all larger than those between the target molecule and its aptamer.Therefore,the principle of this detection method was the displacement of fluorescent probe(ThT)in aptamer-ThT complex by target molecule,resulting in decrease of fluorescence intensity.Under optimal experimental conditions,the limits of detection(LODs)were 0.8 nmol/L for OTA,1.3 nmol/L for AFB1,and 0.10 μmol/L for adenosine,respectively.This method was label-free,simple to operate,with low cost,good selectivity and high sensitivity.The developed assay kit based on this method could be used for actual sample detection.