ObjectiveTo establish and evaluate a hyperuricemia （HUA） mouse model with the damp-turbidity internal accumulation syndrome. MethodsThirty-six C57BL/6J mice were randomly divided into control group， chemically induced model group （Model）， and model combined with high-fat and fatigue group （Model+HF）. Twenty-four uricase gene knockout （UOX^-/-） mice were randomly divided into UOX^-/- group and UOX^-/-+HF group， with 12 mice in each group. The Model group and the Model+HF group established the HUA model by intragastric administration of potassium oxyazinate combined with adenine. The Model+HF group and the UOX^-/-+HF group adopted a high-fat diet combined with weight-bearing exhaustive swimming to establish the HUA model with the damp-turbidity internal accumulation syndrome. On day 1， 7， 14， 21， and 28 after modeling， the damp-turbidity internal accumulation syndrome score of each group was evaluated. On day 1 and day 28， a weight-bearing swimming exhaustion test was performed， and the exhaustive swimming time was recorded. On day 28， liver and kidney indexes were calculated， and hematoxylin-eosin （HE） staining was used to observe histopathological changes in liver and kidney tissues. Serum levels of uric acid （UA）， xanthine dehydrogenase （XDH）， xanthine oxidase （XOD） and urea nitrogen （BUN） were detected through biochemical assays. ELISA was used to detect serum levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）. Immunohistochemistry was used to detect the protein expression of organic anion transporter 1 （OAT1） and glucose transporter 9 （GLUT9） in renal tissues. Quantitative real-time PCR （qRT-PCR） was used to detect the mRNA expressions of adenosine triphosphate binding transporter G2 （ABCG2）， hypoxia-inducible factor-1α （HIF-1α）， urate anion transporter 1 （URAT1）， and GLUT9 in renal tissues. ResultsOn day 14 of modeling， the damp-turbidity internal accumulation syndrome scores of mice in the Model+HF group and the UOX^-/-+HF group were elevated compared with the control group（P＜0.05）； on day 28， the scores significantly increased， and the exhaustive swimming time was shortened （P＜0.01）， indicating successful establishment of the damp-turbidity internal accumulation syndrome model. Compared with the control group， all other groups exhibited increased kidney index， serum levels of UA， XDH， XOD， BUN， TNF-α， and IL-1β， elevated renal mRNA expression of HIF-1α， URAT1， OAT1， and GLUT9， and decreased renal ABCG2 mRNA expression （P＜0.01 or P＜0.05）. Significant pathological damage in the kidney was observed in the Model+HF group and the UOX^-/-+HF group compared to the Model group and the UOX^-/- group， with decreased serum UA and increased BUN and TNF-α levels （P＜0.05 or P＜0.01）， as well as increased expression of OAT1 and GLUT9 in the renal tissue. ConclusionBoth chemical induction and gene knockout， combined with a high-fat diet and weight-bearing exhaustive swimming， can successfully establish mouse models of HUA with damp-turbidity internal accumulation syndrome. Chemical induction is simple to operate and cost-effective， suitable for short-term drug screening， while UOX gene knockout induces spontaneous elevation of serum uric acid levels without drug administration， which may better mimick human metabolic characteristics.

ObjectiveTo establish and evaluate a hyperuricemia （HUA） mouse model with the damp-turbidity internal accumulation syndrome. MethodsThirty-six C57BL/6J mice were randomly divided into control group， chemically induced model group （Model）， and model combined with high-fat and fatigue group （Model+HF）. Twenty-four uricase gene knockout （UOX^-/-） mice were randomly divided into UOX^-/- group and UOX^-/-+HF group， with 12 mice in each group. The Model group and the Model+HF group established the HUA model by intragastric administration of potassium oxyazinate combined with adenine. The Model+HF group and the UOX^-/-+HF group adopted a high-fat diet combined with weight-bearing exhaustive swimming to establish the HUA model with the damp-turbidity internal accumulation syndrome. On day 1， 7， 14， 21， and 28 after modeling， the damp-turbidity internal accumulation syndrome score of each group was evaluated. On day 1 and day 28， a weight-bearing swimming exhaustion test was performed， and the exhaustive swimming time was recorded. On day 28， liver and kidney indexes were calculated， and hematoxylin-eosin （HE） staining was used to observe histopathological changes in liver and kidney tissues. Serum levels of uric acid （UA）， xanthine dehydrogenase （XDH）， xanthine oxidase （XOD） and urea nitrogen （BUN） were detected through biochemical assays. ELISA was used to detect serum levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）. Immunohistochemistry was used to detect the protein expression of organic anion transporter 1 （OAT1） and glucose transporter 9 （GLUT9） in renal tissues. Quantitative real-time PCR （qRT-PCR） was used to detect the mRNA expressions of adenosine triphosphate binding transporter G2 （ABCG2）， hypoxia-inducible factor-1α （HIF-1α）， urate anion transporter 1 （URAT1）， and GLUT9 in renal tissues. ResultsOn day 14 of modeling， the damp-turbidity internal accumulation syndrome scores of mice in the Model+HF group and the UOX^-/-+HF group were elevated compared with the control group（P＜0.05）； on day 28， the scores significantly increased， and the exhaustive swimming time was shortened （P＜0.01）， indicating successful establishment of the damp-turbidity internal accumulation syndrome model. Compared with the control group， all other groups exhibited increased kidney index， serum levels of UA， XDH， XOD， BUN， TNF-α， and IL-1β， elevated renal mRNA expression of HIF-1α， URAT1， OAT1， and GLUT9， and decreased renal ABCG2 mRNA expression （P＜0.01 or P＜0.05）. Significant pathological damage in the kidney was observed in the Model+HF group and the UOX^-/-+HF group compared to the Model group and the UOX^-/- group， with decreased serum UA and increased BUN and TNF-α levels （P＜0.05 or P＜0.01）， as well as increased expression of OAT1 and GLUT9 in the renal tissue. ConclusionBoth chemical induction and gene knockout， combined with a high-fat diet and weight-bearing exhaustive swimming， can successfully establish mouse models of HUA with damp-turbidity internal accumulation syndrome. Chemical induction is simple to operate and cost-effective， suitable for short-term drug screening， while UOX gene knockout induces spontaneous elevation of serum uric acid levels without drug administration， which may better mimick human metabolic characteristics.

Based on the duality of "healthy" and "pathogenic" of the immune system in physiological and pathological states， and combined with the analogy between "immune function" and "healthy qi"， the theory of "transformation of healthy qi into pathogenic qi" was proposed to guide the pattern identification and treatment of autoimmune diseases. The theory of "transformation of healthy qi into pathogenic qi" means that "healthy qi"， which is originally used by the body's original ability to defend and remove harmful factors or normal functional activities， transformed into "pathogenic qi"， which is factors that damage and destroy the human body or abnormal body state. In the pathogenesis of autoimmune diseases， the pathogenic factors and causes of congenital endowment， tissue damage under the influence of external pathogens， abnormal function of zang-fu （脏腑） organs and meridians， abnormal transmission and transformation of qi， blood， body fluids was proposed. Autoimmune diseases have the dynamic mechanism of latent pathogen at early stage， internal and external contraction at the onset stage， and the expansion of the pathogenic qi at the complete period， and also have the characteristics of the specificity， invisibility and contradiction of healthy qi and pathogenic qi. In terms of treatment， it advocates the ideas of treatment with both attack and supplementation throughout the disease， identifying diseases with special prescriptions and formulas for specific diseases， dynamically adjusting treatment by identifying the remission and onsets of the disease， observing the changes in the dynamics of healthy qi transforming into pathogenic qi， and treating disease before it arises with early intervention.

Objective:To evaluate the safety and efficacy of amniotic membrane patching in the treatment of recurrent macular hole associated with retinal detachment of high myopia (MHRD).Methods:A prospective study. From March 2018 to January 2020, 11 patients (11 eyes) of recurrent macular hole associated with MHRD at the First Affiliated Hospital of Zhengzhou University were enrolled. Among them, there were 3 males (3 eyes), and 8 females (8 eyes). The average age was 63.64±5.82. The axis length (AL) was 29.10± 0.59 mm, and the logarithm of the minimum angle of resolution best corrected visual acuity (logMAR BCVA) was 2.23±0.57. Patients previously received pars plana vitrectomy (PPV) combined with internal limiting membrane stripping surgery, which was more than 1 time. All eyes underwent standard pars plana three-channel 23G PPV combined with amniotic membrane covering and silicone oil filling. The silicone oil was removed 6 months after surgery. Follow-up time was up to 3 months after silicone oil removal surgery. 1, 3, and 6 months after the operation, the same equipment and methods were used to conduct relevant examinations before the operation to observe the closure of the macular hole, retinal reattachment and changes in logMAR BCVA. The logMAR BCVA before and after surgery was compared by paired t test. Results:At 1, 3, and 6 months after the operation, the retinas of all eyes were anatomically repositioned, the macular holes were well closed, and the amniotic membrane was attached to the retina. At 3 months after the silicone oil removal operation, there was no recurrence of macular hole in all eyes; logMAR BCVA was 1.35±0.32. No serious complications occurred during and after surgery in all eyes.Conclusion:Amniotic membrane patching is a safe and effective method for recurrent macular hole associated with MHRD.

Objective To investigate and characterize the serum metabolite profile of patients with rheumatoid arthritis (RA),a common autoimmune disease,which will be of help for early diagnosis in clinic.Methods Serum specimens from 26 patients with RA and 19 age-matched healthy volunteers were collected from the First Affiliated Hospital of Hunan University of Chinese Medicine from January through April 2015.Samples were detected on the gas chromatography-mass spectrometry (GC-MS),and serum metabolites were identified by the chemometric methods.Discriminative model of RA and healthy volunteers was established using partial least squares-linear discriminant analysis (PLS-LDA),and furthermore the established model was evaluated with double cross validation (DCV) for predicting ability.Finally,differential metabolites with clinical diagnostic potential were screened out by using subwindow permutation analysis (SPA).Results The established PLS-LDA discriminative model identified 48 metabolites.The total accuracy of the model approached 97.73％,in which the accuracy of the model for predicting RA and healthy volunteers was 96.15％ and 100％,respectively.Our studies screened out 3-hydroxy butyric acid,phosphoric acid,isoleucine,mannose and hexadecanoic acid with clinical diagnostic potential based on the SPA.Conclusions Metabolomics with the application of GC-MS combined with the PLS-LDA method can distinguish patients with RA and healthy volunteers,and can aid in potential early diagnosis of RA.

Background Diabetic retinopathy (DR) seems to be rarely found in high myopia patients with diabetes mellitus.This finding suggests that myopia,especially high myopia,plays a protective effect against DR.It is well-known that the primary pathological base of DR is neovescularization,and the changes of vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) are associated with DR.Objective This study was to analyze the expressions of VEGF and PEDF in retina and investigate the influence of high myopia on the pathogenesis of DR.Methods Forty-eight 3-day-old guinea pigs were randomly divided into normal control group,high myopia group,diabetic group and diabetes with high myopia group.Translucent goggles were worn in the right eyes of the guinea pigs for consecutive 8 weeks to induce high myopia,and streptozocin (STZ) was intraperitoneally injected at a dose of 60 mg/kg for four times,every three days for once,to establish diabetic models in the corresponding groups.Twelve weeks after modeling,the animals were sacrificed by excessive anesthesia,and the retinas were isolated for the histopathological examination.Expressions of VEGF and PEDF in the retinas were detected by immunohistochemistry.The use and care of experimental animals conformed to Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results The diopter of the normal control group,high myopia group,diabetic group and diabetes with high myopia group were (+0.25±0.07),(-7.50±0.04),(+0.25±0.03) and (-7.50±0.02) D,the fasting glucose of the four groups were (5.3 ±0.1),(5.1 ±0.2),(19.7 ±0.4) and (18.5±0.3)mmol/L,respectively.Compared with the normal control group,the retinas of high myopia group were thin,and the ganglion cells were less.The retinas of diabetic group were loose and oedematous.The retinas of diabetes with high myopia group were thin and oedematous.The expressing level of VEGF in retinas (absorbance value,A) were 128.61 ±5.57,118.24±2.59,155.60±9.70 and 135.15±5.22 in the normal control group,high myopia group,diabetic group and diabetes with high myopia group,respectively,showing a significant difference among the groups (F=17.365,P=0.032),and the VEGF level was significantly lower in the diabetes with high myopia group than that of the diabetic group (t =5.210,P＜0.05).The expressing level of PEDF in retinas (A value) were 145.57± 8.35,149.54±6.20,127.71±2.45 and 137.53±7.38,in the normal control group,high myopia group,diabetic group and diabetes with high myopia group,respectively,with a statistically significant difference among the four groups (F =19.210,P =0.019),and the PEDF level was significantly higher in the diabetes with high myopia group than that of the diabetic group (t=4.521,P＜0.05).Conclusions The expression of VEGF is downregulated and PEDF is upregulated in the retinas of diabetes with high myopia guinea pigs,which may be an accountable mechanism for the low incidence of DR in high myopia eyes.

Objective:To explore the functional mechanism for therapeutic effects of angelica amylose in mice and rats with adjuvant-induced arthritis (AIA) and its effect of abirritation.Methods:Adjuvant arthritis was induced in either mice or rats.The effect of angelica amylose on rats’ arthritis and on mouse writhing response caused by acetic acid were observed.Tripterygium wilfordii was used as the positive drug for control.Results:Angelica amylose had obvious inhibition on mice writhing response and rats’ adjuvant-induced arthritis.Conclusion:Angelica amylose has effects of abirritation and anti-AIA.