AIM:To investigate the regulatory effects of proanthocyanidins on autophagy and apoptosis in the retinas of guinea pigs with form-deprivation myopia via the AMPK/Wnt/β-catenin pathway.METHODS:Fifty guinea pigs were randomly divided into a normal control group, a myopia model group, and low-dose, medium-dose, and high-dose proanthocyanidins groups(25, 50 and 100 mg/kg). Refractive power and axial length of right eye were measured using a retinoscope and A-scan ultrasound. Retinal pathological changes were observed via HE staining. Immunohistochemistry assessed p-AMPK and p-mTOR expression in the retina. Immunofluorescence detected p62 and LC3 expression. TUNEL staining evaluated retinal cell apoptosis. Western blot examined expression of proteins related to the AMPK/Wnt/β-catenin pathway and autophagy(p62, Beclin1, LC3-II/LC3-I), and apoptosis-related proteins(Bax, Bcl-2, Cleaved-Caspase3, Caspase3)in the retina.RESULTS:Compared with the control group, the myopia model group showed significantly reduced refractive power and significantly increased axial length(both P<0.05); retinal cell arrangement became sparse and retinal thickness thinned. The p-AMPK levels in the retina were significantly reduced, while p-mTOR levels were significantly increased(both P<0.05), indicating suppression of the AMPK-Wnt/β-catenin pathway. The p62 levels were significantly elevated and LC3 levels were significantly reduced(both P<0.05), suggesting inhibition of autophagy. Bax and Cleaved-Caspase3 were significantly increased, while Bcl-2 was significantly decreased, indicating significantly increased apoptosis(both P<0.05). Compared with the myopia model group, all proanthocyanidins dose groups significantly inhibited refractive error reduction and axial length growth(both P<0.05), restored retinal cell alignment and thickness, activated the AMPK/Wnt/β-catenin pathway, significantly increased p-AMPK expression, and suppressed p-mTOR expression(all P<0.05); significantly suppressed p62 expression, increased Beclin1 and LC3-II/LC3-I expression(both P<0.05), and activated retinal autophagy; significantly suppressed Bax and Cleaved-Caspase3 expression, increased Bcl-2 expression(both P<0.05), and inhibited retinal cell apoptosis.CONCLUSION:Proanthocyanidins enhance retinal autophagy by activating the AMPK/Wnt/β-catenin pathway, thereby inhibiting retinal apoptosis and preventing or alleviating the onset of myopia.

Viruses constitute a significant group of pathogens that have caused numerous fatalities and substantial economic losses in recent years, particularly with the emergence of coronaviruses. While the impact of SARS-CoV-2 appears to be diminishing in daily life, only a limited number of drugs have received approval or emergency use authorization for its treatment. Given the high mutation rate of viral genomes, host-directed agents (HDAs) have emerged as a preferred choice due to their broad applicability and lasting effectiveness. In contrast to direct-acting antivirals (DAAs), HDAs offer several advantages, including broad-spectrum antiviral activities, potential efficacy against future emerging viruses, and a lower likelihood of inducing drug resistance. In our review article, we have synthesized known host-directed antiviral targets that span diverse cellular pathways and mechanisms, shedding light on the intricate interplay between host cells and viruses. Additionally, we have provided a brief overview of the development of HDAs based on these targets. We aim for this comprehensive analysis to offer valuable perspectives and insights that can guide future antiviral research and drug development efforts.

Gastrointestinal graft versus host disease is one of the most severe complications after hematopoietic stem cell transplantation, which can occur in patients of any age groups. Its clinical manifestations include nausea, vomit, abdominal pain, diarrhea and the like. Severe gastrointestinal graft versus host disease could directly influence the patients' clinical prognosis and therapeutic efficacy of transplantation. Here we had a review of the research progress on nutritional support and diet management strategies for gastrointestinal graft versus host disease. It is of great clinical significance to form a step-wise nutritional support model to reduce the risk of malnutrition in patients with gastrointestinal graft versus host disease, which would contribute to improving patients' general condition, relieving digestive tract symptoms, and reducing the risk of complications.

Objective:To investigate the effects of improving the prenatal multidisciplinary consultation mode on the outcomes of fetuses with structural malformations.Methods:Clinical data of pregnant women attending the Prenatal Multidisciplinary Consultation Center, jointly established by the Obstetrics & Gynecology Hospital of Fudan University and the Children's Hospital of Fudan University from January 2004 to December 2019, were retrospectively collected and analyzed. In 2014, the center optimized the multidisciplinary consultation mode to achieve a more individualized approach to genetic testing based on more accurate imaging diagnosis and deeper cooperation between the obstetrics and pediatrics teams. Differences in the number of cases, structure of the diseases, genetic testing results, outcomes, and prognosis between the improved group (enrolled from January 2014 to December 2019) and the baseline group (enrolled from January 2004 to December 2013) were compared. The Chi-square test was used for statistical analysis. Results:(1) This study recruited 5 977 pregnant women, including 3 424 in the baseline group and 2 553 in the improved group. The main indications for consultation were fetal factors [97.2% (5 812/5 977)], among which congenital structural malformations accounted for 77.5% (4 503/5 812). There was a significant difference in the systematic distribution of congenital structural malformations between the two groups ( χ2=141.31, P<0.001). The proportion of malformations involving the central nervous, cardiovascular, and urinary systems ranked in the top three in both groups. (2) The percentage of women receiving genetic testing was higher in the improved group than in the baseline group [26.7% (682/2 553) vs. 15.9% (546/3 424), χ2=103.87, P<0.001] and the positive rate of genetic testing was also higher in the improved group [19.9% (136/682) vs. 9.9% (54/546). χ2=23.42, P<0.001]. (3) Among the 5 977 cases, 418 (7.0%) were lost to follow-up; 1 741 (29.1%) opted for pregnancy termination; 123 (2.2%) had intrauterine fetal death; and 3 695 (61.8%) were live births. The rate of pregnancy termination in the improved group was lower than that of the baseline group [27.7% (707/2 553) vs. 30.2% (1 034/3 424), χ2=4.45, P=0.035]. (4) In the 1 741 cases with pregnancy termination, fatal cardiovascular system malformations ( n=413, 23.7%), central nervous system malformations ( n=377, 21.7%), multiple malformations ( n=258, 14.8%), and chromosomal abnormalities ( n=162, 9.3%) were the main causes. The top five diseases leading to pregnancy termination were cleft lip and palate [59.0% (46/78)], meningocele (5/9), gastroschisis/omphalocele [49.3% (33/67)], diaphragmatic hernia [46.5% (33/71)], and skeletal malformations [40.9% (83/203)]. The rates of pregnancy termination due to gastroschisis/omphalocele, diaphragmatic hernia, and skeletal malformations in the improved group were all lower than those in the baseline group [57.4% (27/47) vs. 30.0% (6/20), χ2=4.23; 59.0% (23/39) vs. 31.3% (10/32), χ2=5.43; 51.8% (72/139) vs. 17.2% (11/64), χ2=21.72; all P<0.05]. (5) Among the 3 695 live births, 1 979 (53.6%) were delivered by cesarean section and 1 716 (46.4%) by vaginal delivery; 3 633 (98.3%) survived and 62 (1.7%) died in the neonatal period. The survival rate of newborns in the improved group was higher than that in the baseline group [98.8% (1 648/1 668) vs. 97.9% (1 985/2 027), χ2=4.23, P=0.040]. Among the 62 dead newborns, 51 (82.3%) had fatal structural or chromosomal abnormalities. (6) In the surviving neonates, 372 (10.2%) showed no abnormalities in a postnatal reexamination, and 468 (12.9%) received surgical treatment in the neonatal period. The other 2 793 cases received no treatment in the neonatal period but were followed up regularly. Conclusion:The optimized prenatal multidisciplinary consultation mode effectively reduces the rate of pregnancy termination due to non-fatal single structural malformations and increases the survival rate of newborns.

Objective To explore the patterns of functional gait asymmetry during the support phase and the differentiation of bilateral foot functions,to gain insights into the human movement compensa-tion mechanisms and stability control characteristics,so as to provide theoretical references for the pre-vention and rehabilitation treatment of unilateral foot and ankle injuries.Methods Twelve young females with normal feet were recruited,and the time percentage of each phase of the support period,the change of longitudinal arch angle,the vertical ground reaction force and the center of plantar pressure trajectory of the dominant and non-dominant feet were collected by using a three-dimensional motion capture and a high-frequency plantar pressure testing system when the subjects walked at the optimum speed with the incremental loading of weights[0%body weight(BW),10%BW and 20%BW].The ef-fects of laterality(dominant foot,non-dominant foot)and load(0%BW,10%BW,20%BW)on arch changes and gait parameters,and the interactions between them,were analyzed using a two-way re-peated-measures ANOVA.Results The factors of laterality and load interacted significantly on arch changes,but not on gait parameters.(2)Compared with 0%BW,the time percentage of the buffering phase of the nondominant feet with the load of 20%BW increased(P<0.05),while that of the domi-nant ones decreased(P<0.05),with an increase in the buffering load of both feet with the load of 20%BW(P<0.05)and the buffering force excursion of both feet with the load of 10%BW(P<0.05).More-over,changes in longitudinal arch angle increased(P<0.05)with the load of 10%and 20%BW,the pedal extension load rate increased(P<0.05)with the above BW load in the non-dominant feet,and the horizontal slope of pedal extension decreased(P<0.05)with 20%BW load in the dominant feet.Compared with 10%BW,when the feed was loaded 20%BW,the time percentage in the buffering phase and the buffering force offset of the dominant feet decreased(P<0.05),while the buffering load of both feet increased(P<0.05).(3)Compared with the non-dominant feet,for the dominant feet,the buffering load rate at the load of 10%and 20%BW and changes in the longitudinal arch angle at the load of 20%BW decreased(P<0.05),while the horizontal slope of the pedal extension without load in-creased(P<0.05).Conclusion Walking with load induces function differentiation in bilateral feet.The dominant foot has more efficient horizontal extension without load and better buffering function in the vertical direction with loads,while the non-dominant feet perform a more adequate weight-bearing and extension function vertically with larger load.It is suggested that unilateral injury feet should not be given too much load,and it is inappropriate to select a single foot to represent and evaluate the func-tion and injury risk of the double feet in loaded walking.

Under the theory of preventive treatment of disease,Traditional Chinese medicine(TCM)has accumulated wealth experience in cancer prevention such as recurrence and metastasis,and cancer treatment,that plays a unique advantage on several stages of cancer.As an important treatment method of traditional Chinese medicine to prevent disease,Gao Fang has the function of correcting deviation and removing disease,and has four functions including regulating,supplementing,preventing and treating,which plays a pivotal role in the prevention and treatment of malignant tumor.Gao Fang is an effective means to treat tumor.Therefore,this article intends to discuss the effect of Gao Fang on tumor under the perspective of preventive treatment of the disease.

Diabetic kidney disease (DKD) is the most common complication of diabetes mellitus (DM). Qianjin Wenwu decoction (QWD), a well-known traditional Korean medicine, has been used for the treatment of DKD, with satisfactory therapeutic effects. This study was designed to investigate the active components and mechanisms of action of QWD in the treatment of DKD. The results demonstrated that a total of 13 active components in five types were found in QWD, including flavonoids, flavonoid glycosides, phenylpropionic acids, saponins, coumarins, and lignins. Two key proteins, TGF-β1 and TIMP-1, were identified as the target proteins through molecular docking. Furthermore, QWD significantly suppressed Scr and BUN levels which increased after unilateral ureteral obstruction (UUO). Hematoxylin & eosin (H&E) and Masson staining results demonstrated that QWD significantly alleviated renal interstitial fibrosis in UUO mice. We also found that QWD promoted ECM degradation by regulating MMP-9/TIMP-1 homeostasis to improve renal tubulointerstitial fibrosis and interfere with the expression and activity of TGF- β1 in DKD treatment. These findings explain the underlying mechanism of QWD for the treatment of DKD, and also provide methodological reference for investigating the mechanism of traditional medicine in the treatment of DKD.
Rats ; Mice ; Animals ; Ureteral Obstruction/metabolism* ; Kidney/metabolism* ; Tissue Inhibitor of Metalloproteinase-1/metabolism* ; Molecular Docking Simulation ; Rats, Sprague-Dawley ; Kidney Diseases/drug therapy* ; Extracellular Matrix/metabolism* ; Flavonoids/metabolism* ; Fibrosis

ObjectiveTo investigate the effect of porcine large intestine-processed Dahuang （Radix et Rhizoma Rhei） on defecation in constipation model mice and the possible mechanism. MethodsFifty Kunming mice were randomized to blank group （n=10） and model group （n=40）. Loperamide suspension at the dose of 8 mg/（kg·d） was given by gavage for four consecutive days to establish a model of constipation. The 24 successfully modeled mice were randomly divided into model group， processed Dahuang group， lactulose group， raw Dahuang group， with six mice in each group. Moreover， six randomly selected mice were chosen as control group. Since the fifth day， 8 mg/（kg·d） of loperamide suspension by gavage was given to the model group， processed Dahuang group， raw Dahuang group， and lactulose group； two hours later， the processed and raw Dahuang groups were administered with 0.6 g/（kg·d） of processed and raw Dahuang suspension， respectively， while the lactulose group was given 0.6 g/（kg·d） of latulose suspension， and the blank group and the model group were given 0.2 ml/10 g of distilled water by gavage， all for four days. The general condition， body weight after the last gavage， number of fecal particles within six hours， fecal wet weight， fecal water content ratio， intestinal propulsion rate and colonic histology changes by HE staining of each group were detected. ResultsThe body weight of the mice in the raw Dahuang group was significantly lighter than that in the other groups （P＜0.05 or P＜0.01）. The number of fecal particles， fecal wet weight and intestinal propulsion rate of mice significantly decreased in the model group than in the blank group （P＜0.05 or P＜0.01）. Compared to those in the model group， the number of fecal particles and fecal wet weight in the processed Dahuang group， lactulose group and raw Dahuang group significantly increased， and the fecal water content ratio in the raw Dahuang group increased as well （P＜0.05 or P＜0.01）. Compared to those in the processed Dahuang group， the number of fecal particles and fecal wet weight in the raw Dahuang group decreased， while the fecal water content ratio increased （P＜0.05 or P＜0.01）， and the fecal water content ratio in the lactulose group increased significantly （P＜0.05）. The intestinal propulsion rate in the processed Dahuang group was higher than that in the model group， lactulose group and raw Dahuang group （P＜0.05 or P＜0.01）. Histopathological analysis showed that the colonic crypts and goblet cells in the blank group were normal and clear， and the colonic muscular layer was thicker. The colonic crypts of the mice in the model group were damaged， with reduced goblet cells to varying degrees and changed colonic muscularis. In the lactulose group and raw Dahuang group， part of the crypts were broken， and the goblet cells were damaged to varying degrees， while in the processed Dahuang group， still the colonic tissue structure of the mice was relatively clear， and the colonic crypts and goblet cells were relatively normal， with thickened muscular layer of the colon. ConclusionPorcine large intestine-processed Dahuang could improve defecation in constipation model mice， and reduce the drastic purgation function of raw Dahuang， for which the mechanism may be related to the protection of colon histopathological damage.

Objective To evaluate the role of calcineurin ( CaN)/nuclear factor of activated T cell cytoplasmic 4 protein ( NFATc4) signaling pathway in inflammatory responses in lung tissues of rats with ventilator-induced lung injury ( VILI) . Methods Twenty-four clean-grade healthy male Wistar rats, aged 5-8 weeks, weighing 220-250 g, were divided into 3 groups ( n=8 each) using a random number table method: control C (group C), VILI group and cyclosporine A plus VILI group (group CsA+VILI). The animals were anesthetized with pentobarbital and tracheostomized. The rats were mechanically ventilated for 6 h with the tidal volume set at 40 ml/kg and respiratory rate at 40 breaths/min to establish the model of VI-LI. The rats kept spontaneous breathing in group C. CaN specific inhibitor cyclosporine A 10 mg/kg was in-traperitoneally injected at 1 h before ventilation in group CsA+VILI. Rats were sacrificed immediately after ventilation, lung tissues were obtained and stained with hematoxylin and eosin to evaluate lung injury, broncho-alveolar lavage fluid was collected for determination of tumor necrosis factor-alpha ( TNF-α) , inter-leukin-1beta ( IL-1β) and IL-6 concentrations by enzyme-linked immunosorbent assay, and the lungs were removed for determination of the wet to dry weight ratio ( W/D ratio) , expression of intercellular adhesion molecule-1 ( ICAM-1) and vascular cell adhesion molecule-1 ( VCAM-1) ( by real-time polymerase chain reaction) , and expression of calcineurin and NFATc4 in lung tissues ( using Western blot ) . Results Compared with group C, the W/D ratio, lung injury scores and concentrations of IL-1β, IL-6 and TNF-αin BALF were significantly increased, and the expression of CaN, NFATc4, ICAM-1 mRNA and VCAM-1 mRNA was up-regulated in group VILI ( P＜0. 05) . Compared with group VILI, the W/D ratio, lung injury scores and concentrations of IL-1β, IL-6 and TNF-αin BALF were significantly decreased, and the expres-sion of CaN, NFATc4, ICAM-1 mRNA and VCAM-1 mRNA was down-regulated in group CsA+VILI ( P＜0. 05) . Conclusion CaN/NFATc4 signaling pathway mediates inflammatory responses in lung tissues of rats with VILI.

Objective To explore the clinical characteristics and risk factors of catheterrelated infection in continuous renal replacement therapy (CRRT) patients.Methods The demographic and clinical data of CRRT patients who inserted with double-lumen non-cuffed dialysis catheter at the First Affiliated Hospital of Sun Yat-sen University from January 1,2016 to December 31,2016 were collected.According to the presence or absence of catheter-related infections,they were divided into infected group and uninfected group.Statistics and analysis of the incidence and pathogenic characteristics of catheter-related infections;Comparison of clinical features of infected and uninfected groups;A multivariate Cox proportional hazard model was used to analyze risk factors for catheter-related infections.Results A total of 364 patients with CRRT (437 cases of central venous catheterization) were enrolled in the study.Catheter-related bloodstream infection (CRBSI) and catheterrelated colonization (CRCOL) rates were 3.565 and 2.228 events per 1000 catheter-days.These catheters were associated with higher proportion of inserted in ICU (P=0.007),immunosuppression (P=0.002),receive catecholamine inotropes therapy (P=0.001) and shock (P=0.030).The infection catheters also had shorter indwelling time (P=0.032) and lower level of blood hemoglobin (P=0.017),serum creatinine (P=0.004),blood brain natriuretic peptide (P=0.005) pericatheter use.The most common pathogens were Gram-negative bacteria,especially Acinetobacter baumannii,which caused 37.5％ CRBSI and 20.0％ CRCOL.Multivariate Cox regression model showed female (P=0.029,HR=2.151),diabetes (P=0.016,HR=2.807),receive catecholamine inotropes therapy (P=0.012,HR=2.655),immunosuppression (P=0.037,HR=2.203) were independent risk factors associated with catheterrelated infection.Conclusions The incidence of CRBSI and CRCOL is 3.565 and 2.228 events per 1000 catheter-days CRRT patients in our hospital.The most common pathogen of catherter-related infection is Gram-negative bacteria.Female,diabetes,received catecholamine inotropic drugs,and immunosuppression were independent risk factors associated with catheter-related infection.