ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

OBJECTIVE To investigate the effect and mechanism of miR-152-3p on the resistance to paclitaxel(PTX)of PTX-resistant ovarian cancer cells(A2780T cells).METHODS ① Ovarian cancer parent cells(A2780 cells)and A2780T cells were treated with PTX(1.875,3.75,7.5,17 and 23 μmol·L-1)for 48 h.Cell viability was evaluated by MTT assay,and the 50%inhibitory concentration(IC50)and drug resistance index of A2780T cells were calculated.Western blotting was used to detect the expres-sions of resistance protein P-glycoprotein(P-gp),multidrug resistance related protein 1(MRP1)and adenosine triphosphate binding transporter G superfamily member 2(ABCG2).② Real-time fluorescent quantita-tive PCR(RT-qPCR)was used to detect the expressions of miR-152-3p in A2780 and A2780T cells.The lipid-mediated transient transfection technique was employed to transfect the miR-152-3p inhibitor to reduce miR-152-3p expression in A2780T cells(miR-152-3p inhibitor group),while the negative control(miR-152-3p NC)group was established.RT-qPCR was used to detect transfection efficiency,and the MTT method,scratch experiment,and flow cytometry were used to investigate the effects of the trans-fecting miR-152-3p inhibitor on survival,migration and apoptosis of A2780T cells.Western blotting was used to detect the protein expressions of Bax and Bcl-2 in A2780T cells.③ Bioinformatics analysis of databases including miRDB,Targetscan,miRWalk,and Starbase predicted the target genes of miR-152-3p that were verified by Western blotting to detect the protein expression of PTEN in A2780T cells of the miR-152-3p inhibitor and miR-152-3p NC groups,and RT-qPCR to detect the PTEN mRNA expression in A2780 and A2780T cells.Then,the lipid-mediated transient transfection technique was used to transfect PTEN siRNA to silence PTEN expression in A2780T cells(PTEN siRNA group).The siRNA negative control(siRNA NC)group was established.RT-qPCR was used to detect transfection efficiency,the MTT method was employed to measure the survival rate and IC50 value,and Western blotting was used to assess the protein expressions of P-gp,MRP1,and ABCG2 in A2780T cells after silencing PTEN expression.RESULTS ①After treatment with PTX,the cell survival rates were decreased in A2780 and A2780T cells(P<0.05),and the resistance index of A2780T cells was 2.8.Compared with A2780 cells,the protein expressions of P-gp and MRP1 and ABCG2 were highly expressed in A2780T cells(P<0.05,P<0.01).② RT-qPCR showed that the expression of miR-152-3p in A2780T cells was higher than that of A2780 cells(P<0.01).Compared with the miR-152-3p NC group,A2780T cell viability(P<0.05,P<0.01)and cell migration capability(P<0.05)were significantly inhibited,while the apoptosis rate increased(P<0.01)in miR-152-3p inhibitor group.Moreover,the protein expression of Bax was increased(P<0.01),but Bcl-2 decreased(P<0.05).③ Bioinformatics analysis suggested that PTEN was a target gene of the miR-152-3p,and the verified results showed that the PTEN protein expression in A2780T cells of the miR-152-3p inhibitor group was lower than that of the miR-152-3p NC group(P<0.05),and PTEN mRNA expression in A2780T cells was higher than that in A2780 cells(P<0.01).After silencing the expression of PTEN in A2780T cells,the cell viability was significantly reduced(P<0.05,P<0.01),while the IC50 value was reduced(P<0.01)compared with the siRNA NC group.In addition,the protein expressions of P-gp,MRP1 and ABCG2 were decreased(P<0.05,P<0.01).CONCLUSION miR-152-3p is highly expressed in A2780T cells,and down-regulation of its expression may inhibit proliferation and migration,prompt apoptosis and reduce the resistance to PTX of A2780T cells,which is made possible by inhibiting expression of its target gene PTEN.

Objective:To explore the characteristics and therapeutic strategies of Pott's puffy tumor（PPT）. Methods:The clinical data of two patients with PPT were retrospectively analyzed and combined with the literature, focusing on the comprehensive analysis of perioperative diagnosis and treatment strategies. Both patients underwent muti-disciplinary treatment, including timely administration of sufficient antibiotics capable of penetrating the blood-brain barrier. Early removal of PPT lesions was performed using a combined internal and external approach under nasal endoscopic guidance. Results:After standardized perioperative management, the symptoms of the two patients were completely relieved, with no recurrence after one=year follow=up. Postoperative complications such as frontal pain, numbness, local depression, or scar hyperplasiawere not present. Conclusion:PPT, being relatively rare and severe, requires careful attention. Key strategies for standardized perioperative management include multi-disciplinary consultation, timely and adequate antibiotic administration, and surgical intervention using a combined intranasal and extranasal endoscopic approach for lesion removal.
Humans ; Pott Puffy Tumor/complications* ; Retrospective Studies ; Tomography, X-Ray Computed ; Endoscopy/adverse effects* ; Postoperative Complications ; Anti-Bacterial Agents/therapeutic use* ; Frontal Sinusitis/complications*

Objective:To discuss the clinical characteristics,diagnosis,and treatment of Shwachman-Diamond syndrome(SDS),and to enhance the clinicians'awareness of the disease.Methods:The clinical materials of one patient diagnosed with SDS,primarily presented with neutropenia and elevated transaminase levels,confirmed by genetic testing were retrospectively analyzed.The clinical manifestations,genetic features,diagnosis,and treatment methods of SDS were analyzed complemented with the relevant literatures.Results:This patient was a male child,aged 27 months.His initial clinical presentations were neutropenia and elevated transaminase levels.The patient had previously experienced diarrhea when the patient was 3 months old,which improved after treated with oral pancreatic enzyme dispersion.Over the past six months,the patient had recurrent respiratory infections.Upon admission,the examination results showed there was dental enamel hypoplasia,and the imaging results showed the abnormal bone density in the long bones of the limbs.The genetic sequencing results showed a homozygous mutation in the Shwachman-Bodian-Diamond syndrome(SBDS)gene(c.258+2T>C).During hospitalization,the patient received the hepatoprotective care and granulocyte augmentation supportive treatment,leading to an improvement in his condition,and the patient was discharged.During a one-year follow-up,the patient's condition was stable.Conclusion:The typical presentation of the SDS patient includes diarrhea,liver function abnormalities,hematologic abnormalities,and skeletal anomalies,particularly neutropenia;there may also be developmental delays and involvement of the heart,liver,central nervous system,skeleton,and immune system.The genetic testing of suspected children is crucial,and it can aid in the early diagnosis and treatment of SDS patients.

Objective To investigate the longitudinal changes in left ventricular(LV)structure and function after bariatric surgery in obese individuals and their relationship with preoperative left ventricular ejection fraction(LVEF)by cardiac magnetic resonance(CMR)imaging.Methods We prospectively enrolled 75 obese subjects scheduled for laparoscopic sleeve gastrectomy and 46 age and sex-matched healthy controls(the control group).All subjects underwent CMR examination to obtain LV structural parameters,LVEF,and strain parameters.According to their preoperative LVEF,the obese subjects were divided into two obesity groups,including the group of patients with LVEF≥60％(n=43)and the group of patients with 50％≤LVEF＜60％(n=32).LV structural and functional differences between the control group and the two obesity groups were compared.Eventually,38 obese subjects completed the CMR follow-up at 1 month and 12 months after bariatric surgery.The longitudinal changes in LV structure and function after surgery in the LVEF ≥ 60％(n=20)group and the 50％≤LVEF＜60％group(n=18)were compared.Results Before bariatric surgery,the global longitudinal strain was significantly lower in the LVEF ≥ 60％group than that in the control group([-18.36±1.86]％vs.[-19.50±1.53]％,P＜0.05).The global radial([27.70±3.52]％vs.[34.44±4.11]％,P＜0.05),circumferential([-17.35±1.46]％vs.[-19.85±1.42]％,P＜0.05),and longitudinal([-16.22±1.81]％vs.[-19.50±1.53]％,P＜0.05)strain in the 50％≤ LVEF＜60％group was significantly lower than that in the control group.At 12 months after bariatric surgery,the global radial([32.52±7.84]％vs.[30.92±4.27]％,P＞0.05),circumferential([-19.02±2.42]％vs.[-18.63±1.49]％,P＞0.05),and longitudinal([-18.18±2.06]％vs.[-17.78±1.66]％,P＞0.05)strain in the LVEF≥60％group showed no significant difference compared with the baseline findings.In the 50％≤ LVEF＜60％group,the global radial([32.73±5.86]％vs.[26.83±4.85]％,P＜0.05)and circumferential([-19.10±2.00]％vs.[-16.91±2.09]％,P＜0.05)strain was significantly higher than that before surgery.Conclusion LV remodeling is reversed after bariatric surgery in obese subjects,and the longitudinal changes in LV structure and function vary with the preoperative LVEF.

To ensure proper dosage of a drug,analytical quantification of it in biofluid is necessary.Liquid chro-matography mass spectrometry(LC-MS)is the conventional method of choice as it permits accurate identification and quantification.However,it requires expensive instrumentation and is not appropriate for bedside use.Using soluble epoxide hydrolase(sEH)inhibitors(EC5026 and TPPU)as examples,we report development of a nanobody-based enzyme-linked immunosorbent assay(ELISA)for such small molecules and its use to accurately quantify the drug chemicals in human samples.Under optimized conditions,two nanobody-based ELISAs were successfully established for EC5026 and TPPU with low limits of detection of 0.085 ng/mL and 0.31 ng/mL,respectively,and two order of magnitude linear ranges with high precision and accuracy.The assay was designed to detect parent and two biologically active metabolites in the investigation of a new drug candidate EC5026.In addition,the ELISAs displayed excellent correlation with LC-MS analysis and evaluation of inhibitory potency.The results indicate that nanobody-based ELISA methods can efficiently analyze drug like compounds.These methods could be easily implemented by the bedside,in the field in remote areas or in veterinary practice.This work il-lustrates that nanobody based assays offer alternative and supplementary analytical tools to mass spectrometry for monitoring small molecule medicines during clinical development and therapy.At-tributes of nanobody based pharmaceutical assays are discussed.