Corneal neovascularization(CNV)is a pathological condition characterized by the invasion of new blood vessels into the normally avascular corneal area from the corneal periphery,leading to severe vision loss and potentially blindness.Currently,surgical,physical,and pharmacological therapies are the main clinical approaches for treating CNV.Surgical treatment aims to remove abnormal vascular tissue or perform corneal trans-plantation to inhibit angiogenesis;however,it carries a risk of postoperative rejection.Physical therapy involves the direct application of non-invasive modalities,such as laser treatment,to the neovascularized area to suppress vascular growth.Nevertheless,this approach may cause damage to surrounding healthy tissues.Pharmacotherapy has recently become a research hotspot in CNV treatment due to its convenient administration.Clinically,the drugs used for CNV treatment mainly include anti-inflammatory agents,anti-VEGF drugs,and immunosuppressants,which inhibit CNV progression by targeting angiogenesis-related signaling pathways.However,these drugs often lead to drug resistance and toxic side effects.Therefore,there is an urgent need to develop more effective and safer therapeutic agents for CNV.This article reviews the current clinical treatment status of CNV and highlights recent advances in the use of small molecule extracts from traditional Chinese medicine for CNV therapy,aiming to provide potential candidate drugs and a scientific theoretical basis for clinical management of CNV.

Corneal neovascularization(CNV)is a pathological condition characterized by the invasion of new blood vessels into the normally avascular corneal area from the corneal periphery,leading to severe vision loss and potentially blindness.Currently,surgical,physical,and pharmacological therapies are the main clinical approaches for treating CNV.Surgical treatment aims to remove abnormal vascular tissue or perform corneal trans-plantation to inhibit angiogenesis;however,it carries a risk of postoperative rejection.Physical therapy involves the direct application of non-invasive modalities,such as laser treatment,to the neovascularized area to suppress vascular growth.Nevertheless,this approach may cause damage to surrounding healthy tissues.Pharmacotherapy has recently become a research hotspot in CNV treatment due to its convenient administration.Clinically,the drugs used for CNV treatment mainly include anti-inflammatory agents,anti-VEGF drugs,and immunosuppressants,which inhibit CNV progression by targeting angiogenesis-related signaling pathways.However,these drugs often lead to drug resistance and toxic side effects.Therefore,there is an urgent need to develop more effective and safer therapeutic agents for CNV.This article reviews the current clinical treatment status of CNV and highlights recent advances in the use of small molecule extracts from traditional Chinese medicine for CNV therapy,aiming to provide potential candidate drugs and a scientific theoretical basis for clinical management of CNV.

Objective To explore the feasibility and safety of MCCE in gastrointestinal examination of elderly patients with malignant tumors.Methods Clinical data of 127 patients who underwent MCCE examination from April 2019 to September 2022 were retrospectively analyzed.According to age,the patients were divided into the elderly group(age≥65 year-old,n = 88)and the middle-aged group(40≤age<65 year-old,n = 39),and the clinical data of patients with malignant tumors were screened from the two groups for analysis and comparison.Results 131 patients received MCCE examination,and 4 elderly patients were excluded from this study due to swallowing failure,so 88 elderly patients were actually included in the study.In the elderly group,45.4%had serious cardiovascular diseases(40/88),27.3%had malignant tumors(24/88),8.0%had serious respiratory diseases(7/88),6.8%had anesthesia problems(6/88),and 9.1%had neurological diseases(8/88).Among the 24 elderly patients with malignant tumors,25.0%had severe cardiovascular disease,25.0%had poor general status,20.8%had brain metastases,and 12.5%had severe respiratory dysfunction.The positive diagnosis rate of gastric P2 lesions in the elderly group(52/88,59.1%)was significantly higher than that in the middle-aged group(13/39,33.3%)(P = 0.013).There was significant difference in positive rate of ulcer diagnosis between the two groups(29.5%and 10.2%)(P = 0.032).In patients with malignant tumors,the positive rate of ulcer diagnosis between the two groups(45.8%and 11.1%)was statistically significant(P = 0.038).The cleanliness and visualization scores of proximal stomach in the middle-aged group were higher than those in the elderly group,and the differences were statistically significant(P<0.05).Conclusion MCCE is generally effective and safe in elderly patients,especially those with malignant tumors,without missing any significant gastric lesions.

BACKGROUND:Aging is associated with increased susceptibility to cardiovascular disease,and mitochondrial dysfunction plays a key role in the pathogenesis of cardiovascular disease.Regular physical activity is beneficial to cardiovascular health and can prevent and treat chronic heart disease.However,the specific mechanism of mitochondria in the protective effect of exercise on the aging heart has not yet been clarified. OBJECTIVE:To explore the effect of aerobic exercise on cardiac pathological remodeling in aging rats and to investigate the possible mechanism of mitochondrial quality control system. METHODS:Sixty Wistar rats were randomly divided into young sedentary group(6 months old),old sedentary group(20 months old)and old exercise group(20 months old)with 20 rats in each group.Rats in the young sedentary and old sedentary groups were fed in cages for 12 weeks,while those in the old exercise group underwent moderate-intensity aerobic treadmill exercise(60%of the maximal running speed,slope 0°,60 minute per day,5 days per week)for 12 weeks.After the experiment,the heart was extracted for relevant indicator tests. RESULTS AND CONCLUSION:Cardiac morphology and myocardial histopathology:compared with the young sedentary group,the rats in the old sedentary group presented with concentric cardiac hypertrophy,myocardial fibrosis,myocardial cell apoptosis and loss,and cardiac diastolic dysfunction(P＜0.05);compared with the old sedentary group,animals in the old exercise group showed reduced myocardial fibrosis and apoptosis rates,increased cell numbers,improved cardiac function(P＜0.05),and a transition in cardiac phenotype from pathological to physiological hypertrophy.Mitochondrial function:compared with the young sedentary group,the generation rate of mitochondrial hydrogen peroxide increased(P＜0.05),respiration rate and respiratory control ratio of state 3 and state 4 decreased(P＜0.05),activities of respiratory chain complexes Ⅰ,Ⅱ and Ⅳ decreased(P＜0.05),mitochondrial calcium retention capacity decreased(P＜0.05),and mitochondrial permeability transition pore opening increased(P＜0.05)in the old sedentary group.Compared with the old sedentary group,all of the above indicators were significantly improved in the old exercise group(P＜0.05).Mitochondrial quality control:compared with the young sedentary group,mitochondrial biogenesis decreased(P＜0.05),mitophagy activity increased(P＜0.05),mitochondrial fusion reduced(P＜0.05),and fission raised(P＜0.05)in the old sedentary group;compared with the old sedentary group,mitochondrial biogenesis and mitophagy activity increased(P＜0.05),mitochondrial fusion raised(P＜0.05)and fission decreased(P＜0.05)in the old exercise group.To conclude,regular aerobic exercises exert cardioprotective effects in aging rats by regulating the mitochondrial quality control system,thus reversing pathological cardiac remodeling and improving cardiac function.

l-Heptopyranoses are important components of bacterial polysaccharides and biological active secondary metabolites like septacidin (SEP), which represents a group of nucleoside antibiotics with antitumor, antifungal, and pain-relief activities. However, little is known about the formation mechanisms of those l-heptose moieties. In this study, we deciphered the biosynthetic pathway of the l,l-gluco-heptosamine moiety in SEPs by functional characterizing four genes and proposed that SepI initiates the process by oxidizing the 4'-hydroxyl of l-glycero-α-d-manno-heptose moiety of SEP-328 ( 2) to a keto group. Subsequently, SepJ (C5 epimerase) and SepA (C3 epimerase) shape the 4'-keto-l-heptopyranose moiety by sequential epimerization reactions. At the last step, an aminotransferase SepG installs the 4'-amino group of the l,l-gluco-heptosamine moiety to generate SEP-327 ( 3). An interesting phenomenon is that the SEP intermediates with 4'-keto-l-heptopyranose moieties exist as special bicyclic sugars with hemiacetal-hemiketal structures. Notably, l-pyranose is usually converted from d-pyranose by bifunctional C3/C5 epimerase. SepA is an unprecedented monofunctional l-pyranose C3 epimerase. Further in silico and experimental studies revealed that it represents an overlooked metal dependent-sugar epimerase family bearing vicinal oxygen chelate (VOC) architecture.

Natural cyclohexapeptide AFN A₁ fromStreptomyces alboflavus 313 has moderate antibacterial and antitumor activities. An artificial designed AFN A₁ homodimer, di-AFN A₁, is an antibiotic exhibiting 10 to 150 fold higher biological activities, compared with the monomer. Unfortunately, the yield of di-AFN A₁ is very low (0.09 ± 0.03 mg·L^-1) in the engineered strain Streptomyces alboflavus 313_hmtS (S. albo/313_hmtS), which is not friendly to be genetically engineered for titer improvement of di-AFN A₁ production. In this study, we constructed a biosynthetic gene cluster for di-AFN A₁ and increased its production through heterologous expression. During the collection of di-AFN A₁ biosynthetic genes, the afn genes were located at three sites of S. alboflavus 313 genome. The di-AFN A₁ biosynthetic gene cluster (BGC) was first assembled on one plasmid and introduced into the model strain Streptomyces lividans TK24, which produced di-AFN A₁ at a titer of 0.43 ± 0.01 mg·L^-1. To further increase the yield of di-AFN A₁, the di-AFN A₁ BGC was multiplied and split to mimic the natural afn biosynthetic genes, and the production of di-AFN A₁ increased to 0.62 ± 0.11 mg·L^-1 in S. lividans TK24 by the later strategy. Finally, different Streptomyces hosts were tested and the titer of di-AFN A₁ increased to 0.81 ± 0.17 mg·L^-1, about 8.0-fold higher than that in S. albo/313_hmtS. Successful heterologous expression of di-AFN A₁ with a remarkable increased titer will greatly facilitate the following synthetic biological study and drug development of this dimeric cyclohexapeptide.
Cloning, Molecular ; Streptomyces/metabolism* ; Multigene Family ; Anti-Bacterial Agents/metabolism* ; Plasmids/genetics*

Purpose: Effective predictors of the response to neoadjuvant chemotherapy (NAC) are still insufficient. This study aimed to investigate the predictive value of serum lipid profiles for the response to NAC in breast cancer patients. Methods: A total of 533 breast cancer patients who had received NAC were retrospectively studied. The pretreatment of serum lipids, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and lipoprotein-α, and clinicopathological characteristics were collected to assess their predictive roles. Results: Breast cancer patients had significantly lower TC, TG, HDL-C, and LDL-C levels than normal individuals. Among these indicators, TG and LDL-C levels and HDL-C level increased and decreased significantly after NAC, respectively. In estrogen receptor (ER)-positive patients, increased LDL-C level was associated with better outcomes. Moreover, the receiver operating characteristic curve analyses suggested that TG and HDL-C levels at diagnosis can be used as predictors of the response to NAC only in the ER-positive subgroup.According to univariate analyses, patients with low TG level (< 1.155 mmol/L) or high HDL-C level (≥ 1.305 mmol/L) in the ER-positive subgroup had more favorable clinical responses than the other patients in the subgroup. Furthermore, according to multivariate analyses, a high HDL-C level (≥ 1.305 mmol/L, p = 0.007) was an independent predictor of NAC efficacy. Conclusion High HDL-C level (≥ 1.305 mmol/L) before NAC and increased LDL-C level after NAC were associated with the better treatment response in ER-positive breast cancer patients.These results are potentially considered beneficial in establishing treatment decisions.

Objective To investigate the effects of human amniotic membrane on the survival of the crossboundary perforator flap in rats through distal subcutaneous implantation.Methods From February,2016 to December,2016,38 SD rats weighing 270-300 g were randomly divided into experimental group and control group (n=19).A three-territory perforator flap (3 cm× 10 cm) with the iliac artery as the pedicel elevated on the right dorsum of the rats.Experiment group,a section of amnion was sutured to the distal subcutaneous of the flap and then the flap was sutured back to its donor site.Control group,after the flap elevated,directly sutured back to its donor site.The blood flow of the pedicel were detected by laser Doppler flowmetry at the day before surgery,1 day after surgery,3 and 7 days after surgery,with 3 rats in every group.When the rats were anesthetized,biopsies were taken from the choke area Ⅱ at the day before surgery,3 and 7 days after surgery,with 9 rats in every group.When the rats were anesthetized,HE was used to compare the diameter size of the artery and vein at the same site.At day 7,measure the survival area of the flap,and 3 of them observe the vessel of the flap by lead oxide-gelatine technique.Results The survival rate of the experimental group and the control group after 7 days were (89.09±4.23)％ and (74.56-±5.59)％ respectively,the experimental group was significantly higher than that of the control group (t=5.48,P=0.00).X-ray showed that 7 days after operation,the pedicel of iliac artery in the experimental group was bigger than that in the control group.The blood flow detection showed that the blood flow of the experimental group was higher than that of the control group (t=2.39,3.06;P=0.03,0.00,respectively) at day 1 and day 3 after surgery.Hematoxylin eosin staining showed that arteriovenous tube diameter at the Choke Ⅱ were gradually increased on the day3 and day7 after surgery in both group,but the experimental group diameter expanded multiple was higher than that of control group (t=3.52,3.50;P=0.02,0.02,respectively).Conclusion Human Amnion subcutaneous embedding may improve the blood flow of the vascular pedicle,expand the microvascular at Choke area Ⅱ,improve microcirculation,as a result to promote the survival of cross perforator flap,while the mechanism is needed to understanding.

Objective To research the relationship between Serum uric acid (SUA) levels and the Neu-trophil-to-lymphocyte Ratio (NLR) of Type 2 Diabetes Mellitus (T2DM) patients. Method 273 newly diag-nosed T2DM patients are selected in accordance with the WHO diagnostic criteria: Male subjects with SUA lev-els ≥ 416 μmol/L(70 mg/L), and female subjects with SUA levels ≥ 357 μmol/L (60 mg/L) are sorted into the high SUA (HUA) group (224 subjects), and the rest into the normal SUA (NUA) group (49 subjects). 100 subjects were selected as a control group. One-Way analysis of variance was applied to the data of the three groups; Pearson correlation analysis was used to calculate the correlation of SUA levels , NLR and IR; risk fac-tors influencing SUA levels were analyzed with Logistic regression analysis; ROC curve analysis was used to de-termine the diagnostic value of NLR to HUA, and the optimal threshold value of NLR. Result (1) The NLR and IR of the HUA group was significantly higher than those of the NUA group (2.54 ± 0.63 vs. 2.05 ± 0.61, P < 0.001; 3.70 ± 1.86 vs. 2.71 ± 1.43, P < 0.001); (2) In the HUA group, UA was positively correlated with NLR and IR (respectively r = 0.480, P < 0.001; r = 0.332, P < 0.001). (3)NLR (P < 0.001, EXP(B)= 8.045, 95%CI = 4.597 ~ 14.079) was a risk factor of Hyperuricemia. Conclusion Our results suggest that NLR may be an independent risk factor of Hyperuricemia.

Through analyzing the existing problems and relevant solutions of TCM decoction pieces management, this article expounded the construction of TCM coding system and its construction and application in the hospital information system, attempted to apply technological standards of TCM coding system to routine TCM standardized management work through the means of informatization. At the same time, it also described the basic situation in the construction of TCM coding management information system, and promoted specific ideas, operation methods, and current condition and prospects.