AIM: To explore the diagnostic value of combining the corneal stress-strain index(SSI)with corneal biomechanical parameters for early keratoconus.METHODS:A retrospective study was conducted on 34 patients(53 eyes)with early keratoconus diagnosed and treated in our hospital from March 2022 to February 2024. Additionally, 112 normal volunteers(112 eyes)who underwent physical examinations in our hospital during the same period were selected as a healthy control group. The CorvisST equipment was utilized for measurement and recorded deformation with Scheimpflug camera to obtain 10 biomechanical parameters: first applanation time(A1T), first applanation length(A1L), velocity of initial applanation(Vin), second applanation time(A2T), second applanation length(A2L), velocity of outward applanation(Vout), highest concavity time(HCT), highest concavity depth of applanation(HCDA), highest concavity radius(HCR), and peak distance(PD), as well as stress-strain index(SSI), and the corneal biomechanical parameters of the two groups were compared. Furthermore, Logistic regression analysis was used to identify the risk factors for keratoconus, and ROC curves were plotted to analyze the biomechanical parameters of the cornea for early diagnosis of keratoconus.RESULTS:The SSI(0.77±0.17)in patients with keratoconus was lower than that in healthy controls(1.01±0.24; P<0.001). Patients with keratoconus had lower A1T, A1L, A2L, and HCR, and higher Vout, HCDA, and PD compared to healthy controls(all P<0.001). Logistic regression analysis showed that decreased SSI, A1T, A1L, A2L, and HCR, as well as increased Vout, HCDA, and PD, were risk factors for the development of keratoconus(P<0.001). ROC curve analysis showed that the AUC value for combined diagnosis of early keratoconus was 0.997, with a Youden's index of 0.954, sensitivity and specificity of 98.1% and 97.3%, respectively, and a 95% CI of 0.994-1.000.CONCLUSION:The combination of SSI and corneal biomechanical parameters holds diagnostic significance for early keratoconus, and the joint diagnostic value is even higher. It can be considered as a diagnostic or screening indicator for early keratoconus.

AIM: To explore the relationship between hyperopia reserve and ocular biometric parameters in 4-14 year-old Uyghur students from Hotan County, Xinjiang, and to provide scientific evidence for myopia prevention.METHODS: From September 1 to October 31, 2023, a stratified random cluster sampling method was used to select 3 264 students(3 264 eyes)from 6 schools in Hotan County. Participants underwent uncorrected distance visual acuity testing, cycloplegic refraction, and ocular biometric measurements. The correlation between spherical equivalent(SE)and ocular biometric parameters was analyzed by multiple linear regression.RESULTS: A total of 1 998 non-myopic students(1 998 eyes)were included in the study, with 1 354 students(67.77%)showing insufficient hyperopia reserve. The detection rate of insufficient hyperopia reserve decreased with age, from 94.12% at age 4 to 18.13% at age 14(P<0.001). Multiple linear regression analysis showed that in the group with sufficient hyperopia reserve, age, gender, uncorrected distance visual acuity, axial length(AL), and keratometry(K)explained 66.5% of the variance in SE; while in the group with insufficient hyperopia reserve, these factors explained only 28.0% of the SE variance.CONCLUSION: In non-myopic Uyghur students aged 4-14 in Hotan County, Xinjiang, the detection rate of insufficient hyperopia reserve was 67.77%. In the group with insufficient hyperopia reserve, age, gender, AL, and K explained only a small portion of the SE variance, suggesting that the refractive status of this population may be influenced by more complex factors.

Objective:To investigate the independent risk factors of recurrent laryngeal nerve(RLN)injury after microwave ablation(MWA)for thyroid nodules of different malignant stratification.Methods:The medical records of 240 patients,who underwent microwave ablation for thyroid nodules in the department of ultrasound,Beijing Friendship Hospital Affiliated to Capital Medical University from September 2022 to August 2024,were retrospectively selected.All thyroid nodule cases were categorized based on the American College of Radiology Thyroid Imaging Reporting and Data System(TI-RADS)classification criteria and whether occurred RLN injury during the ablation procedure.A total of 54 patients with RLN injury and 65 patients without RLN injury,who were classified as TI-RADS 4a or higher than that,were divided into the high-risk group,and 35 patients with RLN injury and 86 patients without RLN injury,who were classified below TI-RADS 4a,were divided into the low-risk group.And then,a series of parameters included the benign and malignant nodules,the upper diameter of nodules,the left and right diameters of nodules,anteroposterior diameters of nodules,the aspect ratio(>1,≤1),overall echo,calcification,location,cystic solidity,and ablation parameters were analyzed.The risk factors of RLN injury of two groups were analyzed by using single factor and multi factor analysis.Results:There were not significant differences in the benign and malignant nodules,the upper diameters of nodules,the left and right diameters of nodules,anteroposterior diameters of nodules,the volume of nodules,overall echo,calcification,ldiametersocation,and cystic solidity between high and low-risk groups(P>0.05).In high-risk group,the distance between nodules and esophageal groove of trachea was less or equal to 2mm,and the increase of nodule volume were independent risk factors for RLN injury(OR=4.199,1.002,P<0.05),respectively.In the low-risk group,the nodule,which location was on the Zuckerkandl tubercle(Z-nodule),was risk factor that significantly increased RLN injury(OR=3.296,P<0.05).Conclusion:For nodules with differently malignant risk,the anatomical location,volume parameters and optimized ablation plan should be paid special attention before surgery,so as to reduce the risk of RLN injury.

Objective:To study the effect of angiopoietin-1(Ang-1)and tyrosine kinase receptor 2(Tie2)inhibitor on glucose transportation in the human umbilical vein endothelial cells(HUVECs)cultured under high glucose conditions,and to clarify its mechanism.Methods:The HUVECs were cultured in high glucose(30 mmol·L?1)in vitro and treated with 0,200,500,1 000,and 2 000 μg·L?1 Ang-1 and 0,2 500,5 000,and 7 500 nmol·L?1 Tie2 inhibitor;cell counting kit-8(CCK-8)method was used to detect the cell activity to screen the optimal concentrations of Ang-1 and Tie2 inhibitor.Glucose kit was used to detect the glucose level in the supernatant of the HUVECs after Ang-1 intervention.The HUVECs were randomly divided into blank control group(NG group),high glucose group(HG group),HG+Tie2 inhibitor group(HG+In-Tie2 group),HG+Ang-1 group,HG+Ang-1+Tie2 inhibitor group(HG+Ang-1+In-Tie2 group),and HG+Ang-1+phosphatidylinositol 3-kinase(PI3K)inhibitor group(HG+Ang-1+LY294002 group).5-Ethynyl-2'-deoxyuridine(EdU)method was used to detect the proliferation activities of the cells in various groups;YO-PRO-1/PI method was used to detect the apoptotic rates of the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of Ang-1 mRNA and Tie2 mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Tie2,glucose transporter 1(GLUT1),and glucose transporter 4(GLUT4)proteins and the ratios of phosphorylated PI3K(p-PI3K)/PI3K and phosphorylated protein kinase B(p-AKT)/AKT in the cells in various groups.Results:The CCK-8 assay results showed that compared with 0 μg·L?1 Ang-1 group,the activity of the HUVECs was significantly increased after treated with 200 μg·L?1 Ang-1 for 48 h(P<0.01);compared with 0 nmol·L?1 Tie2 inhibitor group,the activity of the HUVECs was significantly decreased after treated with 2 500、5 000 and 7 500 nmol·L?1 Tie2 inhibitor(P<0.01);the optimal concentrations of Ang-1 and Tie2 inhibitor were 200 μg·L?1 and 2 500 nmol·L?1,respectively.Compared with NG group,the glucose level in the supernatant of the HUVECs in HG group was significantly increased(P<0.01);compared with HG group,the glucose level in the supernatant of the HUVECs in Ang-1 group was significantly decreased(P<0.01).The EdU assay results showed that compared with NG group,the proliferation activity of the HUVECs in HG group was significantly decreased(P<0.01);compared with HG group,the proliferation activity of the HUVECs in HG+In-Tie2 group was significantly decreased(P<0.01),and the proliferation activity of the HUVECs in HG+Ang-1 group was significantly increased(P<0.01);compared with HG+Ang-1 group,the proliferation activities of the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly decreased(P<0.01).The YO-PRO-1/PI assay results showed that compared with NG group,the apoptotic rate of the HUVECs in HG group was significantly increased(P<0.01);compared with HG group,the apoptotic rate of the HUVECs in HG+In-Tie2 group was significantly increased(P<0.01),and the apoptotic rate of the HUVECs in HG+Ang-1 group was significantly decreased(P<0.01);compared with HG+Ang-1 group,the apoptotic rates of the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly increased(P<0.01).The RT-qPCR results showed that compared with NG group,the expression levels of Ang-1 mRNA and Tie2 mRNA in the HUVECs in HG group and HG+In-Tie2 group were significantly decreased(P<0.01);compared with HG group,the expression levels of Ang-1 mRNA and Tie2 mRNA in HG+In-Tie2 group were significantly decreased(P<0.01),and the expression levels of Ang-1 mRNA and Tie2 mRNA in the HUVECs in HG+Ang-1 group were significantly increased(P<0.05);compared with HG+Ang-1 group,the expression levels of Ang-1 mRNA and Tie2 mRNA in the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly decreased(P<0.05 or P<0.01).The Western blotting results showed that compared with NG group,the expression level of Tie2 protein in the HUVECs in HG group was significantly decreased(P<0.01),and the expression levels of GLUT1 and GLUT4 proteins were significantly increased(P<0.01);compared with HG group,the expression levels of Tie2,GLUT1,and GLUT4 proteins in the HUVECs in HG+In-Tie2 group were significantly decreased(P<0.01),the expression level of Tie2 protein in the HUVECs in HG+Ang-1 group was significantly increased(P<0.01),and the expression levels of GLUT1 and GLUT4 proteins were significantly decreased(P<0.01);compared with HG+Ang-1 group,the expression levels of Tie2,GLUT1,and GLUT4 proteins in the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly decreased(P<0.01).Compared with NG group,the p-PI3K/PI3K and p-AKT/AKT ratios in the HUVECs in HG group were significantly increased(P<0.01);compared with HG group,the p-PI3K/PI3K and p-AKT/AKT ratios in the HUVECs in HG+In-Tie2 group were significantly decreased(P<0.01),and the p-PI3K/PI3K and p-AKT/AKT ratios in the HUVECs in HG+Ang-1 group were significantly decreased(P<0.01);compared with HG+Ang-1 group,the p-PI3K/PI3K and p-AKT/AKT ratios in the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly decreased(P<0.01).Conclusion:Ang-1 down-regulates the expressions of GLUT1 and GLUT4 in the HUVECs cultured under high glucose conditions;the binding of Ang-1 to Tie2 may down-regulate GLUT1 and GLUT4 via the PI3K/AKT signaling pathway to participate in the glucose transportation in the HUVECs cultured under high glucose conditions.

Objective:To explore the factors influencing the success rate of culturing patient-derived gastric and colorectal cancer organoids.Methods:From Feb 2022 to Oct 2023, 398 tumor tissue specimens from patients who underwent gastric cancer and colorectal cancer resection at the Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University, were used for organoid culture. The clinicopathological factors affecting the success rate of organoid culture were analyzed.Results:The overall success rate of organoid culture in this group was 75.1% (299/398), with the success rate of gastric cancer organoid culture being 79.8%(154/193) and that of colorectal cancer being 70.7% (145/205). Different clinicopathological T stage ( χ2=4.765, P<0.05),histological type ( χ2=11.248, P<0.05), and tumor regression grade (TRG) grade after neoadjuvant chemotherapy ( χ2=7.797, P<0.05) were related to the success rate of organoid culture . Multivariate analysis showed that the TRG grade was an independent influencing factor( P=0.040). For colorectal cancer, different pathological T stage ( χ2=5.108, P<0.05), histological type ( χ2=11.270, P<0.05), and TRG grade after neoadjuvant chemotherapy ( χ2=6.797, P<0.05) were related to the success rate of organoidculture . Different from gastric cancer, the results of multivariate analysis of colorectal cancer showed that the histological type was an independent influencing factor ( P=0.018). Conclusions:The pathologic T stage, histological type of tumors, and TRG of cancer patients all have a significant impact on the success rate of establishing tumor organoids. Among them, the TRG grade is an independent influencing factor for the culture of gastric cancer organoids, and the histological type is an independent influencing factor for colorectal cancer organoids.

Objective To investigate the efficacy of lenalidomide combined with bortezomib and dexamethasone in the treatment of multiple myeloma(MM)and their effects on heat shock protein 90(HSP90)mRNA,miR-28-5p,anti-tartrate acid phosphatase 5b(TRACP-5b)and high mobility group protein B1(HMGB1).Methods Eighty patients with newly diagnosed MM were selected and divided into the two-combination group(40 patients treated with bortezomib and dexamethasone)and the three-combination group(40 patients treated with bortezomib and dexamethasone combined with lenalidomide)according to the treatment modalities.Real-time fluorescence quantitative polymerase chain reaction was used to detect HSP90 mRNA and miR-28-5p levels.Enzyme-linked immunosorbent assay was used to detect TRACP-5b and HMGB1 levels.The clinical efficacy of the 2 groups was compared.Levels of HSP90 mRNA,miR-28-5p,TRACP-5b,HMGB1,the immune cell function,renal function indexes and the incidence of adverse reactions were compared before and after treatment.Results The total effective rate of the three-combination group was higher than that of the two-combination groups(92.50%vs.75.00%,P＜0.05).Compared with the pretreatment,the levels of HSP90 mRNA,TRACP-5b,blood creatinine(SCr),and urea nitrogen(BUN)decreased in the 2 groups after treatment,and which was lower in the three-combination group than that in the two-combination groups.The levels of miR-28-5p,HMGB1,CD4+,CD3+and CD4+/CD8+were elevated in the 2 groups,and the levels were higher in the three-combination group than those in the two-combination group(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups.Conclusion Lenalidomide combined with bortezomib and dexamethasone is clinically effective,safe and reliable in the treatment of MM.

OBJECTIVE To provide standardized whole-process guidance on drug traceability codes for medical institutions in Sichuan province， ensuring medication safety and compliance with medical insurance supervision requirements. METHODS Based on evidence-based principles and expert consensus， Expert Consensus on Whole-process Management of Drug Traceability Codes in Medical Institutions of Sichuan Province （hereinafter referred to as the Consensus） was formulated through systematic literature review， field investigations， establishment of a multidisciplinary expert committee and multiple rounds of questionnare consultation via the modified Delphi method， and finalized through consensus meetings. RESULTS & CONCLUSIONS The Consensus clarifies key operating procedures for code verification， code assignment and code return， whole-process operational standards for drug warehouse acceptance and storage， drug warehouse outbound delivery and pharmacy acceptance check， drug distribution and dispensing in pharmacy and intravenous admixture center， medication administration in nursing units and examination departments， as well as drug return process. Key recommendations are proposed such as improving the core functions of the drug traceability system， unifying the hospital-wide traceability code database， strengthening the management of traceability codes for backup medications， establishing a management organization and institutional framework， and optimizing the architectural design and data governance requirements of the drug traceability system. The release of the Consensus will provide scientific， standardized and implementable practical guidelines for medical institutions of Sichuan province， helping to improve closed-loop management of the drug traceability system， strengthen medication safety and fulfil medical insurance fund supervision.

AIM:To compare the formation and release of neutrophil extracellular traps(NETs)af-ter exposure to the high-altitude hypoxic environ-ment for different periods,and their relationship with the dynamic changes of microcirculatory disor-ders associated with pulmonary edema.METH-ODS:SD rats were raised under normoxic condi-tions at an altitude of 400 m and under hypoxic conditions at an altitude of 4 200 m.The rats raised under hypoxic conditions at an altitude of 4 200 m for 7 days were returned to normoxic con-ditions at 400 m to observe the changes in physio-logical and pathological indicators of the rats.The dynamic changes of neutrophil extracellular traps(NETs)release and microcirculatory disorders relat-ed to pulmonary edema after high-altitude hypoxia exposure and after returning to the plain were ex-plored by blood routine determination,rat arterial blood gas analysis,ELISA experiment,lung water content determination,H&E staining,and immuno-histochemical staining.RESULTS:In the hypoxic en-vironment at 4 200 m,rats exhibited significant re-ductions in arterial oxygen saturation(SaO2)and partial pressure of oxygen(PO2)(P＜0.01),accompa-nied by a marked increase in lung-tissue water con-tent(P＜0.01).The complete blood count revealed elevated levels of red blood cells,white blood cells,lymphocytes,and neutrophils(P＜0.01).In addition,the formation and release of NETs in neutrophils in-creased,accompanied by an aggravation of the in-flammatory response.After returning to the low-al-titude normoxic area at 400 m,the above indica-tors gradually returned to normal levels on the 7th day.Pathological changes such as alveolar epitheli-al cell shedding and inflammatory cell infiltration were observed in the lung tissues of rats in the high-altitude area,and the pathological changes were restored after returning to the low-altitude normoxic environment.CONCLUSION:The release of NETs from neutrophils is closely related to the re-covery of pulmonary edema and pulmonary ede-ma-related microcirculatory disorders after high-al-titude hypoxia exposure.

Objective:This study aimed to evaluate the long-term efficacy and safety of rituximab(RTX)combined with calcineurin inhibitors(CNI)in the treatment of refractory nephrotic syndrome(RNS).Methods:A total of 80 patients with steroid-dependent/resistant RNS were prospectively enrolled and randomly assigned to an observation group(RTX+CNI,n=40)and a control group(CNI monotherapy,n=40).Patients were followed up for 24 months.Dynamic comparisons were made between the two groups regarding complete remission rate,relapse rate,24-hour urinary protein,kidney injury molecule-1(KIM-1),and adverse reactions.Results:The complete remission rate(CR)in the observation group was significantly higher than that in the control group at all time points(24-month CR:100％vs 90％,P＜0.05).The 24-month relapse rate was significantly lower in the observation group compared to the control group(0％vs 10％,P＜0.05).Combination therapy significantly reduced 24-hour urinary protein levels(6 months:2.13±0.63 vs 3.86±1.01 g/24 h,P＜0.001)and the renal injury marker KIM-1(6 months:1.53±0.41 vs 2.23±0.65 ng/mL,P＜0.001),and increased the CD4+/CD8+ ratio(24 months:2.03±0.52 vs 1.72±0.41,P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(15％vs 20％,P=0.556).Conclusion:RTX combined with CNI significantly improves the long-term remission rate and reduces the risk of relapse in RNS.Its dual immunomodulatory and multi-target renal protective effects provide evidence-based support for optimizing the treatment of refractory nephrotic syndrome.

This study explored the effects and underlying mechanism of Raf kinase inhibitory protein(RKIP)on apoptosis in mast cells sensitized by Echinococcus granulosus cyst fluid.Bone marrow-derived mast cells(BMMCs)were isolated and cultured from RKIP knockout(KO)and wild-type(WT)C57BL/6 mice.Cells were divided into control and sensitized groups.The sensitized group was incubated for 24 h in RPMI1640 medium containing 10%serum from mice infected with E.granulosus,then activated for 3 h or 6 h with E.granulosus cyst fluid.The control group was incubated for 24 h in RPMI1640 medium,and then received an equal vol-ume of PBS.Cells and supernatants were collected for analysis.Flow cytometry was used to detect the expression of CD117 and FcεRⅠα on BMMCs.The levels of β-hexosaminidase,IL-4,and TNF-α in the supernatant were quantified with ELISA.Western blot analy-sis was used to assess expression changes in RKIP,apoptosis-related proteins,and pathway proteins in BMMC before and after sensi-tization.Flow cytometry analysis revealed that after 4 weeks of induction,the CD117 and FcεRⅠα double-positivity rates on both WT and KO BMMC exceeded 90%.ELISA indicated that the E.granulosus cyst fluid resulted in significantly greater β-hexosaminidase re-lease(F=16.88,P<0.05),and levels of IL-4(F=16.51,P<0.05)and TNF-α(F=9.78,P<0.05)in the KO sensitized group than the WT sensitized group.With respect to the WT control group,the WT sensitized group showed significantly down-regulated pro-tein expression levels of RKIP(F=8.20,P<0.05)and Bcl-2(F=101.40,P<0.01)after 3 h,but significantly up-regulated levels of p-PI3K(F=8.04,P<0.05),p-Akt(F=32.52,P<0.01),p-P65(F=13.29,P<0.05),and cleaved-caspase-3(F=46.34,P<0.01).With respect to the WT sensitized group,the KO sensitized group showed significantly up-regulated protein expression of p-PI3K(F=8.45,P<0.05),p-Akt(F=8.58,P<0.05),p-P65(F=11.02,P<0.05),and Bcl-2(F=84.50,P<0.001)after 3 h,but significantly down-regulated expression of cleaved-caspase-3(F=15.66,P<0.05).In conclusion,RKIP may inhibit the PI3K/Akt/NF-κB pathway,thereby inducing apoptosis in mast cells sensitized by E.granulosus cyst fluid.This process may help ease aller-gic reactions caused by mast cells in echinococcosis,thus offering a promising new approach for preventing and treating such reactions.