AIM:To investigate the mechanism of reduced tear secretion in depression-related dry eye rats based on 5-HT/TRPV4/AQP5.METHODS:Healthy SD male rats were established with chronic unpredictable mild stress(CUMS)method to establish a depression-induced dry eye model(n=8), and the control group was blank rats(n=8). The ELISA method was used to compare the 5-hydroxytryptamine(5-HT)in serum and hippocampal tissue of the two groups, and the HE sections of lacrimal gland and AQP5 immunohistochemistry were observed. Western blot and RT-PCR were used to detect the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland tissue of the two groups of rats.RESULTS:The tear secretion in the depression-induced group was significantly reduced(P=0.001), the serum and hippocampal 5-HT levels were significantly reduced(all P<0.05), the expression of AQP5 antibody in the lacrimal gland immunohistochemistry was significantly lower than that in the control group(P<0.001), the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland was significantly reduced(all P<0.05), and no obvious inflammatory cells were found in the lacrimal gland tissue sections.CONCLUSION:Depression-related dry eye may occur through a non-inflammatory 5-HT/TRPV4/AQP5 mechanism.

AIM:To investigate the mechanism of reduced tear secretion in depression-related dry eye rats based on 5-HT/TRPV4/AQP5.METHODS:Healthy SD male rats were established with chronic unpredictable mild stress(CUMS)method to establish a depression-induced dry eye model(n=8), and the control group was blank rats(n=8). The ELISA method was used to compare the 5-hydroxytryptamine(5-HT)in serum and hippocampal tissue of the two groups, and the HE sections of lacrimal gland and AQP5 immunohistochemistry were observed. Western blot and RT-PCR were used to detect the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland tissue of the two groups of rats.RESULTS:The tear secretion in the depression-induced group was significantly reduced(P=0.001), the serum and hippocampal 5-HT levels were significantly reduced(all P<0.05), the expression of AQP5 antibody in the lacrimal gland immunohistochemistry was significantly lower than that in the control group(P<0.001), the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland was significantly reduced(all P<0.05), and no obvious inflammatory cells were found in the lacrimal gland tissue sections.CONCLUSION:Depression-related dry eye may occur through a non-inflammatory 5-HT/TRPV4/AQP5 mechanism.

Objective To explore the effective induction scheme for differentiation of adipose-derived mesenchymal stem cell (ADMSC) to insulin producing cell (IPC). Methods Different schemes of small molecule compound were used to induce the differentiation of ADMSC. The purity of cells was analyzed by flow cytometry and the morphological changes of cells were observed under the microscope. The quality, performance and insulin related indicators of cells were detected by hematoxylin-eosin and immunohistochemical staining. The maturity and activity of cells were detected by dithizone (DTZ) and diacetylfluorescein/propidium iodide staining. The induction effect of ADMSC differentiated into IPC was analyzed. Results The purity of ADMSC reached more than 99%, and the sphere forming properties of schemes Ⅰ, Ⅱ and Ⅲ were good. Cell induction mass, the expression effects of pancreatic and duodenal homeobox 1 (PDX1), musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) and insulin and C peptide of schemes Ⅰ were both better than those of other schemes. The DTZ staining depth may be related to IPC maturity, among which the number of apoptotic cells in scheme Ⅰ was significantly less than that of scheme Ⅱ and Ⅲ. Conclusions Induction scheme Ⅰ may improve the differentiation efficiency of ADMSC to IPC and lay a certain foundation for future clinical IPC transplantation applications.

Dry eye disease is a multifactorial chronic ocular surface disorder that is challenging to manage because its pathogenesis is not well understood. The gut-eye axis theory provides insights into its pathogenesis to guide prevention and treatment. Intestinal flora dysbiosis induces dry eye disease through complex mechanisms involving inflammation, ocular surface microbiota, nerve damage, and microbial metabolites. This article reviews the immunometabolic regulation of the gut-eye axis and summarizes gut flora-targeted interventions(fecal microbiota transplantation, probiotic supplementation, and dietary modification)to provide a theoretical basis for dry eye disease prevention and treatment.

An increasing number of studies have shown that there is a close relationship between Alzheimer's disease(AD)and diabetes mellitus(DM).Traditional Chinese medicine holds that"kidney yin deficiency"is the common pathogenesis of these two diseases,while modern medicine believes that their pathogenesis involves abnormal aggregation of amyloid proteins,insulin deficiency and resistance,inflammatory response,oxidative stress,and autophagy,among others.The well-known traditional Chinese medicine formula Liuwei Dihuang Pills plays a significant role in the treatment of these two diseases with the same therapeutic approach.Therefore,this article will explore the connection between Liuwei Dihuang Pills and the treatment of AD and DM from different aspects;analyze the common etiology and pathogenesis of AD and DM,and explain the mechanism of prevention and treatment of Liuwei Dihuang Pills,with the aim of providing new ideas and methods for the integrated traditional and Western medicine prevention and treatment of AD and DM in the future.

Objective To explore the mechanism by which electroacupuncture improves ocular surface inflammation in dry eye mice.Methods 30 SPF-grade healthy male ICR mice were randomly divided into a blank group,a model group,a sham electroacupuncture group,a western medicine group and an electroacupuncture group,with 6 mice in each group.Mice in the blank group and other four groups were subcutaneously injected 200 μL of sterile physiological saline and 200 μL of scopolamine hydrobromide(0.5 mg dissolved in 0.2 mL of sterile physiological saline)at 8:00,11:00,14:00,and 17:00 every day for 35 consecutive days,respectively.From the 22nd day,mice in the sham electroacupunc-ture group were given blunt scalp acupuncture intervention at bilateral Jingming and Taiyang points,without subcutaneous penetration.In the western medicine group,fluorometholone eye drops were applied to both eyes of the mice at 8:00,13:00,and 18:00 daily,with 1 drop each time.Mice in the electroacupuncture group were given electroacupuncture in-tervention,with the same acupoint location and acupuncture time as the sham electroacupuncture group.The electroacu-puncture frequency was 2 Hz/20 Hz,the waves were sparse-dense and the intensity was 1 mA,once a day for 15 min.All groups were intervened for 14 days.The corneal fluorescein(FL)staining scores of mice in each group were detected be-fore modeling,after modeling,and after intervention.The corneal tissue morphology was observed under a light micro-scope.Immunohistochemistry staining and quantitative reverse transcription polymerase chain reaction(qRT-PCR)were used to detect the protein and mRNA expression of high mobility group box 1(HMGB1)and receptor for advanced glyca-tion end products(RAGE)in the cornea,respectively.Results The FL scores of mice in model,sham electroacupunc-ture,western medicine,and electroacupuncture groups all significantly increased after modeling and intervention,com-pared with those before modeling(all P＜0.01).The FL scores of mice in electroacupuncture and western medicine groups significantly decreased after intervention,compared with those after modeling(both P＜0.01).Compared with the model group,electroacupuncture and western medicine groups showed a significant drop in FL score after intervention(both P＜0.01).HE staining showed that after intervention,mice in electroacupuncture and western medicine groups had a basically normal number of corneal epithelial layers,no obvious shedding of epithelial cells,and neatly arranged and slightly swollen collagen fibers in the stromal layer.The relative protein expression levels of HMGB1 and RAGE in the corneal tissue of both model and sham electroacupuncture groups were significantly higher than those of the blank group(allP＜0.01).The rela-tive protein expression levels of HMGB1 and RAGE in the corneal tissue of both electroacupuncture and western medicine groups were significantly lower than those of the model group(all P＜0.01).The relative mRNA expression levels of HMGB1 and RAGE in the corneal tissue of both model and sham electroacupuncture groups were significantly higher than those of the blank group(all P＜0.01).The relative mRNA expression levels of HMGB1 and RAGE in the corneal tissue of both electroacupuncture and western medicine groups were significantly lower than those of the model group(all P＜0.01).Conclusion Electroacupuncture mitigates corneal epithelial injury,reduces the expression of HMGB1 in the cor-neal tissue,inhibits the binding of HMGB1 and RAGE,and ultimately alleviates ocular surface inflammation responses of dry eye mice.

Objective To investigate the mechanism by which Erdong Xiaoke Formula(EDXKF)regulates lacrimal gland autophagy in type 2 diabetes-induced dry eye rats through the peroxisome proliferator-activated receptor γ(PPARγ)/mammalian target of rapamycin(mTOR)signal pathway.Methods Healthy male SD rats were fed with high-sugar and high-fat chow and then injected intraperitoneally 30 mg·kg-1 streptozotocin to construct type 2 diabetes-induced dry eye rat models.Healthy male SD rats were selected as a blank group.Type 2 diabetes rats were randomly divided into a model group,a Traditional Chinese Medicine(TCM)group(given 11 g·kg-1 of EDXKF through gavage),an antagonist group(given 2 mg·kg-1 PPARγ antagonist through intraperitoneal injection),and a TCM plus antagonist group(given 11 g·kg-1 EDXKF through gavage and 2 mg·kg-1 PPARγ antagonist through intraperitoneal injection).Fasting blood glucose(FBG),corneal fluorescein(FL)staining,tear film break-up time(BUT)and phenol red cotton thread test(Prtt)were examined before modeling,after modeling,and after intervention.The weight of the lacrimal gland was compared among different groups after sampling.Hematoxylin and eosin(HE)staining was performed to analyze lacrimal gland hismorphol-ogy.The expression of microtubule-associated protein 1 light chain 3(LC3)and Sequestosome-1(p62)in the lacrimal gland was examined by immunofluorescence.Western blot was used to detect the expression of PPARγ,p62,LC3 Ⅱ,LC3 I,mTOR and p-mTOR in the lacrimal gland.Results FBG levels in the antagonist group were significantly increased after intervention,compared with those in the TCM group(P＜0.01).Ocular surface examination showed that compared with the model group,the TCM group had increased BUT and Prtt scores and decreased FL scores,the antagonist group had de-creased BUT and Prtt scores and increased FL scores(all P＜0.05).Compared with the antagonist group,the TCM plus antagonist group showed increased BUT and Prtt scores and decreased FL scores(all P＜0.05).The weight analysis of lac-rimal glands revealed that the lacrimal gland weight increased in the TCM group and decreased in the antagonist group,compared with that in the model group(all P＜0.01).The lacrimal gland weight in the TCM plus antagonist group was higher than that in the antagonist group(P＜0.01).HE staining of the lacrimal gland showed atrophy of glandular lobules,increased fusion and expansion of follicles,and dense distribution of nuclei in model and antagonist groups.These symp-toms were more obvious in the antagonist group.Compared with antagonist and TCM plus antagonist groups,the TCM group showed improved symptoms,with tightly arranged follicles,partial atrophy and fusion,and a small amount of expan-sion.Immunofluorescence staining for detecting the average fluorescence intensity of LC3 and p62 showed that compared with the model group,the TCM group had increased LC3 levels and decreased p62 levels,and the antagonist group had de-creased LC3 levels and increased p62 levels(all P＜0.01).Compared with those in the antagonist group,LC3 levels were increased and p62 levels were decreased in the TCM plus antagonist group(both P＜0.01).Western blot results showed that compared with the model group,the TCM group had increased PPARγ and LC3 levels and decreased p62 and p-mTOR/mTOR levels.PPARγ and LC3 levels were decreased and p62 and p-mTOR/mTOR levels were increased in the antagonist group,compared with those in the model group.The TCM plus antagonist group had higher PPARγ and LC3 levels and low-er p62 and p-mTOR/mTOR levels than the antagonist group(all P＜0.05).Conclusion EDXKF can regulate the PPARy/mTOR signal pathway to promote lacrimal gland autophagy and thus alleviate dry eyes in type 2 diabetes rats.

This paper expounds the origin and development of the thought of circular movement,summarizes its core and application ideas.It attempts to generalize the pathogenesis of chronic cough and asthma from the perspective of"non-circular movement",and explores the mechanism of Bazhen Decoction in treating chronic cough and asthma.In specific clinical practice,it is emphasized that based on the use of Bazhen Decoction,a comprehensive analysis and adjustment of the prescription should be carried out from aspects such as"qi and blood,yin and yang,deficiency and excess,qi movement"to achieve better therapeutic effects.

Objective This study reveals the potential mechanism of electroacupuncture in alleviating the inflamma-tory injury of sensory nerves and alleviating the abnormal sensation on the ocular surface in type 2 diabetes rats with dry eye.Methods Healthy male SD rats were induced to establish type 2 diabetes dry eye rat model.Model rats were ran-domly divided into model group,electroacupuncture group,sham-acupuncture group,and fluorometholone group in the 12th week of the experiment.The blank group was established as well,and each group was intervened for 2 weeks.The corneal fluorescein sodium staining(FL),break-up time(BUT),phenol red thread test(PRT),corneal mechanical per-ception threshold(CTT)and blink frequency were measured in each group of rats.After sampling,the expression of neu-ronal injury markers,neuron specific enolase(NSE),neurofilament light chain protein Nf Light(NF-L),phosphorylated microtubule associated protein(Phospho-TAU),as well as inflammatory factors of cysteine protease-1(Caspase-1),inter-leukin-18(IL-18),and interleukin-1β(IL-1β),were observed in the trigeminal ganglion(TG)and spinal cord caudate nu-cleus(SpVc)of each group of rats.Results At the end of the 14th week,compared with the blank group,the FL of the model group,electroacupuncture group,sham-acupuncture group,and fluorometholone group significantly increased,while PRT and BUT significantly decreased.Moreover,the CTT and blink frequency of the model group,sham-acupuncture group,and fluorometholone group significantly decreased(all P＜0.01).Compared with the model group,the electroacu-puncture group and the fluorometholone group showed a decrease in FL,as well as an increase in BUT,PRT,CTT,and blink frequency,with statistically significant differences(all P＜0.05).Compared with the electroacupuncture group,the sham-acupuncture group showed significantly higher FL along with significantly lower values in BUT,PRT,CTT,and blink frequency(all P＜0.05),while the fluorometholone group exhibited decreased FL,PRT,CTT,and blink frequency but in-creased BUT(all P＜0.05).Compared to the sham-acupuncture group,the fluorometholone group exhibited significantly lower FL,but higher BUT and PRT(all P＜0.01).In TG and Sp Vc,compared with the blank group,the expression of NSE,NF-L and Phospho-TAU increased in the model group and the sham-acupuncture group(all P＜0.05);compared with the model group,the expression of NSE,NF-L and Phospho-TAU significantly reduced in the electroacupuncture group(P＜0.01);compared with the electroacupuncture group,the expression of NSE,NF-L and Phospho-TAU increased in the electroacupuncture group and the expression of Phospho-TAU in the sham-acupuncture group also increased(P＜0.05);compared with the sham-acupuncture group,the expression of Phospho-TAU or NF-L significantly reduced in the fluoro-metholone group(all P＜0.05).The Western Blot results indicate that compared with the blank group,the protein expres-sion of Caspase-1,IL-1β,and IL-18 in TG and SpVc of the model group increased;moreover,the expression of Caspase-1 and IL-18 proteins in the sham-acupuncture group also increased(all P＜0.05).Compared with the model group,the ex-pression of Caspase-1,IL-1β,and IL-18 proteins in TG and SpVc reduced in the electroacupuncture group and the fluoro-metholone group,and the expression of IL-1 β proteins in TG and SpVc also reduced in the sham-acupuncture group(all P＜0.05).Compared with the electroacupuncture group,the expression of Caspase-1,IL-1 β,and IL-18 proteins in TG and SpVc increased in the sham-acupuncture group(all P＜0.05).Compared with the sham-acupuncture group,the expression of Caspase-1,IL-1 β,and IL-18 proteins in TG and SpVc reduced in the fluorometholone group(all P＜0.05).Conclusion Electroacupuncture can effectively alleviate the abnormal ocular surface sensation of type 2 diabetes dry eye rats by alleviating the neuroinflammatory injury in TG and SpVc.

Objective:To evaluate the efficacy and safety of once-daily tacrolimus extended-release capsules (OD-TAC) in pediatric liver transplant recipients after conversion from twice-daily tacrolimus (TD-TAC).Methods:A retrospective analysis was performed on pediatric liver transplant recipients at Tianjin First Center Hospital between January 2014 and December 2020 who were converted from TD-TAC to OD-TAC with a follow-up of at least 12 months. After conversion, all patients received OD-TAC monotherapy. The daily dose conversion ratio from TD-TAC to OD-TAC ranged from 2∶1 to 1∶2. Clinical data including demographics, tacrolimus dosage, trough concentrations, liver function, and adverse events were collected. Continuous variables with normal distribution were expressed as Mean±SD and compared using independent-samples t-test or ANOVA; non-normally distributed variables were expressed as median ( Q1, Q3) and compared using Mann-Whitney U or Kruskal-Wallis H tests. Categorical variables were expressed as frequency and percentage, and compared using χ 2 test or Fisher's exact test. P<0.05 was considered statistically significant. Results:A total of 290 children were enrolled, including 140 males (48.3%) and 150 females (51.7%). The median age at transplantation was 7.34 (6.03, 12.34) months, and the median time to conversion was 36 (29, 48) months post-transplant. Tacrolimus daily doses at 3, 6, and 12 months after conversion were slightly higher than before conversion, but without statistical significance (all P>0.05). Trough tacrolimus levels at 6 and 12 months after conversion were 2.34±1.02 μg/L and 2.23±1.07 μg/L, respectively, both lower than pre-conversion (2.77±1.43 μg/L), with statistical significance ( P=0.02 and P<0.01). Serum creatinine levels at 6 and 12 months post-conversion were 2.63±0.63 mmol/L and 2.76±0.68 mmol/L, respectively, both higher than before conversion (2.57±1.90 mmol/L, P<0.05). Triglyceride level at 12 months post-conversion was 0.87±0.25 mmol/L, significantly lower than pre-conversion (1.05±0.55 mmol/L, P<0.05). Two patients developed transient bilirubin elevation at 3 months, and another two developed transient triglyceride elevation at 6 months; all recovered without intervention. No new-onset diabetes was observed during follow-up. Thirteen patients experienced acute rejection. One patient (0.3%) died three years after conversion due to hepatic venous outflow obstruction, while all others survived. Conclusion:In pediatric liver transplant recipients, OD-TAC provides comparable efficacy and safety to TD-TAC.