AIM: To analyze the current status, research hotspots, and development trends of international studies on ocular surface microbiota based on bibliometrics.METHODS: Leveraging the Web of Science database, we conducted a targeted literature search on ocular surface flora. The retrieved data were meticulously screened and weighted to enhance relevance. The bibliometric analysis delved into publication trends, authorship patterns, institutional collaborations, and pivotal research themes. Employing Cite Space software, we visually dissected the landscape of institutional and national partnerships, citation impact, keyword co-occurrences, keyword clustering dynamics, and the emergence of new research trends.RESULTS: A total of 3 884 publications were ultimately included, with an overall upward trend in the number of publications in the field of ocular surface microbiota from 2003 to 2023, with the most rapid growth occurring from 2019 to 2022. The top three regions/countries by publication volume are the United States(1 039 papers), China(570 papers), and India(302 papers). The top three authors by publication volume are Willcox Mark(48 papers), Sharma Savitri(33 papers), and Fleiszig Suzanne M.J(27 papers). The top three institutions by publication volume, all from the United States, are the University of California, L.V. Prasad Eye Institute, and Harvard University. The citation network map of the literature includes 801 nodes and 1 508 connections, with the most frequently cited document being Temporal Stability and Composition of the Ocular Surface Microbiome. The top 5 keywords by frequency of occurrence are, in order, keratitis, bacterial flora, identification, inflammation, and endophthalmitis. The keyword clustering analysis yielded a total of 8 clusters, which are specifically reflected in three aspects: ocular-related diseases, the relationship between ocular surface microbiota and ocular surface structures, and detection methods for ocular surface microbiota. The keyword with the highest burst strength is ciprofloxacin. Keywords that have emerged in recent years and continue to the present include diversity, gut microbiome, and ocular surface microbiome.CONCLUSION: Currently, the study of ocular surface microflora is gaining momentum globally, with a particular focus on the diversity of microflora, the composition of the core microbiome, and its impact on ocular diseases. In the future, research should concentrate on elucidating the functional metabolism of the ocular surface microflora and further investigate the causality and mechanisms by which changes in the ocular surface microflora are related to diseases.

ObjectiveTo investigate the mechanism of liver injury induced by tripterygium glycosides tablets （TG） and the molecular mechanism of compound glycyrrhizin tablets （CG） in alleviating the abnormalities of cholesterol metabolism caused by TG via cholesterol metabolism. MethodsAccording to the body weights， male Sprague-Dawley （SD） rats were randomly grouped as follows： control （pure water）， low-dose TG （TG-L， 189.0 mg·kg^-1·d^-1）， high-dose TG （TG-H， 472.5 mg·kg^-1·d^-1）， TG-L+CG （189.0 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， and TG-H+CG （472.5 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， with 6 rats in each group. Rats were administrated with corresponding drugs once daily for 3 weeks. At the end of the last administration， the mRNA and protein levels of liver X receptor-alpha （LXR-α）， low-density lipoprotein receptor （LDLR）， adenosine triphosphate-binding cassette transporter A1 （ABCA1）， adenosine triphosphate-binding cassette transporter G1 （ABCG1）， 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMGCR）， cholesterol 7α-hydroxylase （CYP7A1）， cholesterol 12α-hydroxylase （CYP8B1）， and sterol 27-hydroxylase （CYP27A1） in the liver tissue were determined by Real-time PCR and Western blotting， respectively. The level of 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMG-CoAR）， a regulatory enzyme of cholesterol synthesis， was measured by enzyme-linked immunosorbent assay （ELISA）. HepG2 cells were used to observe the effect of TG on the cell proliferation in vitro. Specifically， HepG2 cells were grouped as follows： Low-dose TG （TG-l， 15 mg·L^-1）， medium-dose TG （TG-m， 45 mg·L^-1）， high-dose TG （TG-h， 135 mg·L^-1）， fenofibrate （FB， 10 μmol·L^-1）， CG extract， TG-h+FB （135 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-m+FB （45 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-l+FB （15 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-h+CG （135 mg·L^-1 TG + 60 μmol·L^-1 CG）， TG-m+CG （45 mg·L^-1 TG + 60 μmol·L^-1 CG）， and TG-l+CG （15 mg·L^-1 TG + 60 μmol·L^-1 CG）. The mRNA and protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells were determined by Real-time PCR and Western blotting， respectively. ResultsThe rat experiment showed that compared with the control group， the TG-H group showed down-regulated mRNA levels of CYP7A1， CYP8B1， and CYP27A1 in the liver tissue （P<0.05， P<0.01）， which were up-regulated by the application of CG （P<0.05， P<0.01）， and the TG-H+CG group showed up-regulated mRNA level of LDLR （P<0.01）. Compared with the control group， the TG-L and TG-H groups showed down-regulated protein levels of LDLR， CYP7A1， and CYP8B1 in the liver tissue （P<0.05， P<0.01）. In addition， the protein levels of ABCG1 and LXR-α were down-regulated in the TG-H and TG-L groups， respectively （P<0.05）. Compared with TG alone， TG+CG up-regulated the protein levels of ABCG1 and LDLR （P<0.05， P<0.01）， and the protein levels of CYP7A1 and CYP8B1 in the TG-H+CG group were up-regulated （P<0.05， P<0.01）. The cell experiment showed that compared with the control group， the TG-h group presented up-regulated mRNA level of LXR-α （P<0.01）， and the TG-m and TG-h groups showcased down-regulated mRNA levels of LDLR and CYP7A1 （P<0.01） and up-regulated mRNA level of CYP27A1 （P<0.01） in HepG2 cells. The combination of CG with TG restored the above changes （P<0.01）. Western blotting results showed that compared with the control group， the TG-m and TG-h groups showed down-regulated protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells （P<0.01）. Compared with the TG-h group， the TG-h+CG group showed up-regulated protein level of LDLR （P<0.05）. Compared with the TG-m group， the TG-m+CG group showcased up-regulated protein levels of LDLR， ABCG1， CYP7A1， and CYP27A1 （P<0.05， P<0.01）. ConclusionThe administration of TG at 189.0， 472.5 mg·kg^-1 for 3 weeks could modulate the signaling pathways associated with cholesterol efflux， endocytosis， and cholesterol biotransformation in hepatocytes， leading to the accumulation of cholesterol and subsequent liver injury in rats. CG could ameliorate the liver injury induced by lipid metabolism disorders caused by TG by up-regulating the expression of LXR-α， LDLR， ABCG1， CYP7A1， CYP8B1， and CYP27A1 to promote cholesterol biotransformation.

GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

BACKGROUND:Macrophage migration inhibitory factor(MIF)is a pleiotropic cytokine,which is secreted in different types of stem cells and can regulate the proliferation,differentiation and migration of various types of stem cells.Our previous research has confirmed that human embryonic stem cells secrete MIF and that its concentration in the culture medium is relatively stable.However,whether MIF is involved in the survival,proliferation and differentiation of human embryonic stem cells remains unclear. OBJECTIVE:To investigate the effects of MIF on survival,proliferation,and differentiation of human embryonic stem cells. METHODS:(1)Human embryonic stem cells H9 were cultured.The growth curve of cells was detected and plotted by CCK-8 assay.Enzyme-linked immunosorbent assay was used to determine the level of MIF in the medium.(2)To determine the effects of exogenous MIF on the survival and proliferation of human embryonic stem cells,different groups were established:the control group,which was cultured in stem cell medium without any modifications;the exogenous MIF group,which was treated with different concentrations(30,100,300 ng/mL)of MIF in the stem cell medium;the MIF inhibitor ISO-1 group,which was treated with different concentrations(2,7,21 μmol/L)of ISO-1 in the stem cell medium;and the MIF+ISO-1 group,which was treated with different concentrations of ISO-1 along with 100 ng/mL of MIF.Cell viability was assessed using the CCK-8 assay.(3)To further elucidate the effect of MIF gene on survival and proliferation of human embryonic stem cell,the MIF knockout H9 cell line was constructed by CRISPR-Cas 9 technology to observe the lineage establishment.(4)To determine the effect of high concentrations of MIF on human embryonic stem cell differentiation,100 ng/mL MIF and 100 ng/mL of CXCR4 neutralizing antibody were separately added to the normal stem cell culture medium.The expression levels of self-renewal factors(KLF4,c-MYC,NANOG,OCT4,and SOX2)and differentiation transcription factors(FOXA2,OTX2)were measured using real-time quantitative polymerase chain reaction,immunofluorescence staining,and western blot analysis. RESULTS AND CONCLUSION:(1)The logarithmic growth phase of H9 cells was between 3-6 days.Under normal growth conditions,human embryonic stem cells secreted MIF at a concentration of approximately 20 ng/mL,independent of cell quantity.(2)Compared to the control group,the addition of different concentrations of MIF had no effect on the proliferation of human embryonic stem cells(P>0.05).ISO-1 significantly inhibited the proliferation of human embryonic stem cells,with a stronger inhibition observed at higher concentrations of ISO-1(P<0.05).The addition of MIF in the presence of ISO-1 reduced the inhibitory effect of ISO-1(P<0.05).(3)Real-time quantitative polymerase chain reaction showed that knocking out 50%of the MIF gene resulted in a significant decrease in the growth vitality of human embryonic stem cells and failure to establish cell lines.(4)Adding 100 ng/mL exogenous MIF to the culture medium resulted in a decrease in the mRNA,protein,and fluorescence expression levels of the self-renewal transcription factor KLF4,while the mRNA,protein,and fluorescence expression levels of the differentiation factor FOXA2 increased.(5)When 100 ng/mL CXCR4 neutralizing antibody was added to the culture medium,the mRNA and protein expression levels of KLF4 increased,while the mRNA and protein expression levels of FOXA2 decreased,contrary to the expression trend observed in the MIF group.In conclusion,the endogenous secretion of MIF by human embryonic stem cells is essential for their survival.The addition of MIF to the culture medium does not promote the proliferation of human embryonic stem cells.However,it can lead to a decrease in the expression of the self-renewal factor KLF4 and an increase in the expression of the transcription factor FOXA2.This provides a clue for further investigation into the effects and mechanisms of MIF on the differentiation of human embryonic stem cells.The MIF-CXCR4 axis plays a regulatory role in this process.

Anti-CD20 monoclonal antibodies for the treatment of refractory nephrotic syndrome （RNS） in children. The first- generation rituximab is the most widely used in clinical practice； it shows definite efficacy in children with RNS， is recommended by guidelines， particularly for achieving a high remission rate in minimal change nephrosis， and can significantly reduce the cumulative use of glucocorticoids and immunosuppressants. The second-generation ofatumumab has potential as an alternative treatment for patients who are intolerant or resistant to rituximab， while the third-generation obinutuzumab has shown efficacy in complex cases such as rituximab resistance or post-transplant recurrence. However， there is still controversy regarding the optimization of rituximab treatment dosage and whether ofatumumab and obinutuzumab offer greater advantages than rituximab for the treatment of RNS in children. The most common adverse reaction induced by anti-CD20 monoclonal antibodies is infusion reactions， and long-term adverse events mainly include increased risks of sustained immunosuppression and infections. Rituximab has significant economic advantages for the treatment of RNS， but additional pharmacoeconomic research based on China’s healthcare environment is needed to evaluate the cost-effectiveness of ofatumumab and obinutuzumab in this population. Given that the current use of ofatumumab and obinutuzumab in this field is considered off-label use， clinical application should only proceed after a rigorous evaluation of the patient’s benefits and risks.

Objective: To investigate the clinical effects of sinus elevation surgery and implant restorationdue to insufficient bone massafter tooth extraction in patients with odontogenic maxillary sinusitis (OMS) and to provide a reference for use in clinical practice. Methods: This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. Forty-five teeth were extracted from patients with OMS in the maxillary posterior area (the study group). Sinus elevation and implantation were performed due to insufficient bone height in the implant area 6-8 months after tooth extraction in the study group. Forty-eight teeth were extracted from patients without "OMS" in the maxillary posterior area (the control group), and sinus elevation and implantation were performed due to insufficient bone height in the implant area 6-8 months after tooth extraction inthe control group. In the study group, 13 cases of discontinuous maxillary sinus floor bone and residual alveolar bone height of the maxillary sinus floor less than 4 mm were addressed with lateral wall sinus elevation, and the other 32 cases were addressed with crest-approach sinus elevation. In the control group, 8 cases of residual alveolar bone height less than 4 mm in the maxillary sinus floor were addressed with lateral wall sinus,and the other 40 cases were addressed with crest approach sinus elevation. Restorations were placed 6 to 8 months after surgery. The patients were followed up 21 days, 3 months, and 8 months after implantation and every 6 months after the placement of the restorations. The sinus bone gain (SBG), apical bone height (ABL) and marginal bone loss (MBL) were statistically analyzed 24 months after the restoration. Results: The average preoperative mucosal thickness in the 45 patients in the study group was (1.556 ± 0.693) mm, which was significantly larger than that in the control group (1.229 ± 0.425) mm (P<0.001). There were no perforations in either group. Twenty-four months after restoration, there was no significant difference in the SBG, ABH or MBL between the two groups (P>0.05). Conclusion After the extraction of teeth from patients with OMS, the inflammation of the maxillary sinus decreased, and the bone height and density in the edentulous area were restored to a certain degree. The effects of sinus floor lifting surgery and implant restoration do not differ between patients with and without OMS.

Objective To investigate the effect of quercetin on HCE-2 injury of human corneal epithelial cells induced by high osmotic pressure and its mechanism.Methods HCE-2 cells were randomly divided into control group(normal osmotic pressure),model group(high osmotic pressure),experimental-L group(high osmotic pressure+31.25 pg·mL-1 quercetin),experimental-M group(high osmotic pressure+62.50 μg·mL-1 quercetin),experimental-H group(high osmotic pressure+125.00 μg·mL-1 quercetin),erastin group(high osmotic pressure+125.00 μg·mL-1 quercetin+30.00 μmol·L-1 iron death inducer erastin).Cell survival rate was detected by cell counting kit 8;reactive oxygen species(ROS)levels was detected by C11-BODIPY 581/591 probe staining;glutathione(GSH)and malondialdehyde(MDA)levels were determined by kit method;the expression levels of glutathione peroxidase 4(GPX4),dihydrolactate dehydrogenase(DHODH)and ferroptosis suppressor protein 1(FSP1)were detected by real-time quantitative polymerase chain reaction and Western blot.Results The cell survival rates of control group,model group,experimental-H group and erastin group were(100.00±3.97)％,(50.05±5.83)％,(86.35±7.35)％and(58.32±4.66)％,respectively;ROS levels were 1.00±0.09,2.45±0.16,1.19±0.05 and 2.09±0.30,respectively;GPX4 protein levels were 1.09±0.11,0.34±0.03,0.91±0.12 and 0.30±0.04,respectively;FSP1 protein levels were 0.92±0.06,0.25±0.03,0.89±0.07 and 0.39±0.07,respectively;DHODH protein levels were 0.89±0.11,0.31±0.04,0.86±0.11,0.41±0.04,respectively.Compared with model group,the above indexes in control group were statistically significant(all P＜0.05);the differences between experimental-H group and model group were statistically significant(all P＜0.05);the above indexes in erastin group were significantly different from those in experimental-H group(all P＜0.05).Conclusion Quercetin can ameliorate HCE-2 cell damage induced by high osmotic pressure by inhibiting iron death pathway.

Objective To observe the pharmacokinetic effect of amoxicillin and clavulanate potassium tablets on amoxicillin in Chinese healthy subjects under fasting and high fat and high calorie diet.Methods 71 healthy subjects were given a single dose of amoxicillin potassium clavulanate tablets(0.375 g)on fasting or high fat diet,and venous blood samples were collected at different time points.The concentrations of amoxicillin in human plasma were determined by HPLC-MS/MS method,and the pharmacokinetic parameters were calculated by non-atrioventricular model using PhoenixWinNonlin 8.0 software.Results The main pharmacokinetic parameters of amoxicillin potassium clavulanate tablets after fasting and high fat diet were(5 105.00±1 444.00),(4 593.00±1 327.00)ng·mL-1,and postprandial-fasting ratio 89.40％,90％confidence interval(79.55％-100.19％);t1/2 were(1.52±0.16),(1.39±0.22)h;AUC0-t were(12 969.00±1 841.00),(11 577.00±1 663.00)ng·mL-1·h,and postdietary/fasting ratio 89.20％,90％confidence interval(83.92％-94.28％);AUC0-∞ were(13 024.00±1 846.00),(11 532.00±1 545.00)ng·mL-1·h,and postprandial-fasting ratio 88.60％,90％confidence interval(83.48％-93.50％).The median Tmax(range)were 1.63(0.75,3.00)and 2.50(0.75,6.00)h,respectively,and the Tmax of postprandial medication was delayed(P＜0.01).Conclusion Compared with fasting condition,amoxicillin Tmax was significantly delayed after high fat diet,while Cmax,AUC0-t and AUC0-∞ were not significantly changed,indicating that food could delay the absorption of amoxicillin,but did not affect the degree of absorption.

Objective To explore whether the cognitive function of central obese mice is decreased by affecting the expression of brain-derived neurotrophic factor(BDNF)in hippocampus.Methods Healthy mice at the neonatal stage were divided into normal group and model group at random.To obtain the obese models,model group mice were injected at cervical subcutaneous with 10％L-monosodium glutamate(MSG;3 mg·g-1·d-1)for 5 days.The normal group was injected with the same dose of 0.9％NaCl.In addition,mice were removed according to the requirements.Finally,we got 8 mice in each group.The following parameters were compared:body weight,Lee's index and levels of the serum lipid.The BDNF expression levels in hippocampal tissue were measured using western blotting.Results At the 8th weekend,the body weight of the model and normal groups was(49.01±2.47)and(41.27±3.28)g;the Lee's indexes were(357.14±9.24)and(330.15±7.37)g1/3·cm-1;triglyceride levels were(1.37±0.52)and(0.73±0.31)mmol·L-1;total cholesterol levels were(2.98±0.18)and(1.98±0.30)mmol·L-1;low-density lipoprotein levels were(0.31±0.03)and(0.24±0.02)mmol·L-1;high-density lipoprotein levels were(2.70±0.15)and(1.98±0.40)mmol·L-1;the differences were statistically significant(P＜0.05,P＜0.01),which were consistent with the characteristics of the central obesity model.The BDNF protein expression levels in the hippocampus of the model and normal groups were 6.02 x 104±626.53 and 7.04 x 104±1 440.81,which has statistically significant(P＜0.01).Conclusion The cognitive function of central obese mice may be decreased by down-regulating the expression of BDNF in hippocampus.

Objective: To investigate the occupational delay of gratification among community healthcare workers and its influencing factors, so as to provide insights into the sustainable development of primary healthcare personnel. Methods: The in-service community healthcare workers from 5-7 community health service centers in 9 cities (prefectures) of Guizhou Province were selected using a multi-stage stratified random sampling method. Gender, age, and educational level and other basic information were collected through questionnaire surveys. The status of occupational delay of gratification was investigated using the Occupational Delay of Gratification Scale. Multiple linear regression model was used to analyze the influencing factors of occupational delay of gratification. Results: A total of 2 076 respondents were surveyed, including 367 males (17.68%) and 1 709 females (82.32%). There were 112 respondents (5.39%) with secondary vocational school degree or below, 872 respondents (42.00%) with junior college degree, 1 087 respondents (52.36%) with bachelor's degree, and 5 respondents (0.24%) with master's degree or above. There were 665 respondents (32.03%) with managerial positions. The monthly income of 1 705 respondents (82.13%) was ≤5 000 Yuan. The total score of occupational delay of gratification was (33.22±4.33) points, and the total average score was (2.77±0.36) points. The average scores of work delay, career delay and persistence were (2.67±0.48), (2.96±0.45) and (2.75±0.46) points, respectively. Multiple linear regression analysis identified educational level (junior college, β=0.089; bachelor's degree, β=0.088), management position (not have, β=-0.046) and monthly income (>6 000 Yuan, β=0.085) as factors affecting occupational delay of gratification (all P<0.05). Conclusion The community healthcare workers with an education below secondary vocational school, no management position and lower income have relatively lower level of occupational delay of gratification.