AIM: To evaluate the safety and efficacy of allogeneic intrastromal lenticule implantation combined with corneal collagen cross-linking(CXL)in patients with moderate to advanced keratoconus.METHODS: A retrospective case series analysis was conducted. A total of 19 patients(20 eyes)with moderate to advanced keratoconus who underwent combined allogeneic intrastromal lenticule implantation and CXL at the Jinan Mingshui Eye Hospital from June 2021 to December 2023 were included. The uncorrected distance visual acuity(UCVA), thinnest corneal thickness, central corneal epithelial thickness, anterior corneal flat keratometry(Kf), steep keratometry(Ks), and mean keratometry(Km), as well as the first applanation time(A1T), the first applanation length(A1L), the velocity during the first applanation moment(VIN), the second applanation time(A2T), the second applanation length(A2L), the velocity during the second applanation moment(VOUT), highest concavity time(HCT), highest concavity radius(HCR), peak distance(PD), deformation amplitude(DA), stiffness parameter at first applanation(SP-A1), integrated radius(IR), central corneal thickness(CCT), intraocular pressure(IOP), corneal thickness-corrected IOP, biomechanically intraocular pressure IOP(bIOP), and corneal thickness variation rate(ARTH)were compared between the two groups before surgery and at 1 wk, 1, 3 and 6 mo after surgery.RESULTS: All patients successfully completed the surgery without any intraoperative complications. No significant differences were observed between pre-operative and post-operative measurements for UCVA or the corneal biomechanical parameters, including A1L, A2L, PD, A1T, A2T, VIN, VOUT, DA, IOP, and bIOP(all P>0.05). Significant differences were found between pre-operative and post-operative values for corneal thinnest point thickness, central corneal epithelial thickness, Kf, Ks, Km, and the corneal biomechanical parameters, including HCT, HCR, SP-A1, ARTH, IR, and CCT(all P<0.05). The anterior corneal curvature demonstrated an initial increase followed by a decrease post-operatively. Furthermore, significant differences were observed between pre-operative and post-operative values for HCT, HCR, SP-A1, ARTH, IR, and CCT(all P<0.005).CONCLUSION: Allogenic intrastromal lenticule implantation combined with corneal collagen cross-linking demonstrates favorable safety and stability in treating moderate-to-advanced keratoconus. This combined procedure effectively increases corneal thickness and rigidity, resulting in corneas that are more resistant to deformation postoperatively.

ObjectiveTo investigate the efficacy and underlying mechanisms of Gynostemma pentaphyllum alcohol extract in improving glucose and lipid metabolism disorders in db/db mice through transcriptomics and gut microbiota analysis. MethodsEighteen db/db mice were randomly assigned to the model（DM） group， metformin（MET） group， and G. pentaphyllum alcohol extract（GP） group， with six mice in each group， based on stratification of fasting blood glucose and body weight. An additional six db/m mice were selected as the normal control（NC） group. Mice in the NC and DM groups were administered deionized water （10 mL·kg^-1） daily. The MET group received metformin （0.195 g·kg^-1） by gavage. The GP group was treated with G. pentaphyllum alcohol extract （3.9 g·kg^-1） by gavage for six weeks. Fasting blood glucose was measured every two weeks. After six weeks of intervention， serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， and blood urea nitrogen （BUN） were assessed. Enzyme-linked immunosorbent assay （ELISA） was used to measure insulin （FINS）， adiponectin （ADP）， and tumor necrosis factor-α （TNF-α）. Hematoxylin-eosin （HE） staining was used to observe liver histomorphology， periodic acid-Schiff （PAS） staining was employed to assess hepatic glycogen synthesis， and Oil Red O staining was used to detect hepatic lipid deposition. Liver transcriptomic data were used to identify differentially expressed genes in the liver and conduct enrichment analysis. Real-time PCR was employed to verify the expression levels of adiponectin gene （Adipoq）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， AMP-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor α （PPARα）， glucokinase （GCK）， forkhead box （Fox）O1， FoxO3， phosphoenolpyruvate carboxykinase （PEPCK）， and glucose-6-phosphatase （G6PC）. Metagenomic sequencing was conducted to analyze changes in gut microbiota composition. ResultsCompared with the NC group， the DM group exhibited significantly elevated fasting blood glucose （P<0.01）， serum AST， ALT， TC， TG， LDL-C， and HDL-C （P<0.01）. FINS， homeostatic model assessment for insulin resistance （HOMA-IR）， and the inflammatory cytokine TNF-α were significantly increased （P<0.01）， while ADP was significantly decreased （P<0.05）. Histological analysis confirmed severe hepatic steatosis and excessive lipid accumulation in the DM group， along with markedly reduced glycogen synthesis. Compared with the DM group， the GP group showed significantly decreased fasting blood glucose （P<0.01）， reduced serum TC， LDL-C， and HDL-C levels （P<0.05）， significantly decreased serum TG and AST levels （P<0.01）， significantly reduced FINS， HOMA-IR， and TNF-α levels （P<0.01）， and significantly increased ADP （P<0.01）. Hepatic steatosis and lipid deposition were significantly alleviated， while glycogen synthesis was markedly enhanced. Transcriptomic differential and enrichment analyses suggested that the mechanisms by which G. pentaphyllum alcohol extract improved hepatic glucose and lipid metabolism in db/db mice may involve regulation of the AMPK and FoxO signaling pathways. Real-time PCR results confirmed that expression of PGC-1α， PEPCK， G6PC， FoxO1， and FoxO3 was significantly downregulated following treatment with G. pentaphyllum alcohol extract （P<0.05， P<0.01）， whereas mRNA expression of Adipoq， PPARα， GCK， and AMPK was significantly upregulated （P<0.05， P<0.01）. Metagenomic analysis showed that the relative abundance of Lactobacillus， Alistipes， and Akkermansia species was higher in the GP group than in the DM group. ConclusionG. pentaphyllum alcohol extract may improve glucose and lipid metabolism disorders in db/db mice by regulating the hepatic AMPK/PPARα pathway to suppress lipid deposition and alleviate hepatic steatosis， by inhibiting gluconeogenesis through the AMPK/PGC-1α and FoxO pathways to lower fasting blood glucose， and by increasing the abundance of beneficial gut bacteria such as Lactobacillus， Alistipes， and Akkermansia to restore gut microbiota balance.

ObjectiveTo investigate the efficacy and underlying mechanisms of Gynostemma pentaphyllum alcohol extract in improving glucose and lipid metabolism disorders in db/db mice through transcriptomics and gut microbiota analysis. MethodsEighteen db/db mice were randomly assigned to the model（DM） group， metformin（MET） group， and G. pentaphyllum alcohol extract（GP） group， with six mice in each group， based on stratification of fasting blood glucose and body weight. An additional six db/m mice were selected as the normal control（NC） group. Mice in the NC and DM groups were administered deionized water （10 mL·kg^-1） daily. The MET group received metformin （0.195 g·kg^-1） by gavage. The GP group was treated with G. pentaphyllum alcohol extract （3.9 g·kg^-1） by gavage for six weeks. Fasting blood glucose was measured every two weeks. After six weeks of intervention， serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， and blood urea nitrogen （BUN） were assessed. Enzyme-linked immunosorbent assay （ELISA） was used to measure insulin （FINS）， adiponectin （ADP）， and tumor necrosis factor-α （TNF-α）. Hematoxylin-eosin （HE） staining was used to observe liver histomorphology， periodic acid-Schiff （PAS） staining was employed to assess hepatic glycogen synthesis， and Oil Red O staining was used to detect hepatic lipid deposition. Liver transcriptomic data were used to identify differentially expressed genes in the liver and conduct enrichment analysis. Real-time PCR was employed to verify the expression levels of adiponectin gene （Adipoq）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， AMP-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor α （PPARα）， glucokinase （GCK）， forkhead box （Fox）O1， FoxO3， phosphoenolpyruvate carboxykinase （PEPCK）， and glucose-6-phosphatase （G6PC）. Metagenomic sequencing was conducted to analyze changes in gut microbiota composition. ResultsCompared with the NC group， the DM group exhibited significantly elevated fasting blood glucose （P<0.01）， serum AST， ALT， TC， TG， LDL-C， and HDL-C （P<0.01）. FINS， homeostatic model assessment for insulin resistance （HOMA-IR）， and the inflammatory cytokine TNF-α were significantly increased （P<0.01）， while ADP was significantly decreased （P<0.05）. Histological analysis confirmed severe hepatic steatosis and excessive lipid accumulation in the DM group， along with markedly reduced glycogen synthesis. Compared with the DM group， the GP group showed significantly decreased fasting blood glucose （P<0.01）， reduced serum TC， LDL-C， and HDL-C levels （P<0.05）， significantly decreased serum TG and AST levels （P<0.01）， significantly reduced FINS， HOMA-IR， and TNF-α levels （P<0.01）， and significantly increased ADP （P<0.01）. Hepatic steatosis and lipid deposition were significantly alleviated， while glycogen synthesis was markedly enhanced. Transcriptomic differential and enrichment analyses suggested that the mechanisms by which G. pentaphyllum alcohol extract improved hepatic glucose and lipid metabolism in db/db mice may involve regulation of the AMPK and FoxO signaling pathways. Real-time PCR results confirmed that expression of PGC-1α， PEPCK， G6PC， FoxO1， and FoxO3 was significantly downregulated following treatment with G. pentaphyllum alcohol extract （P<0.05， P<0.01）， whereas mRNA expression of Adipoq， PPARα， GCK， and AMPK was significantly upregulated （P<0.05， P<0.01）. Metagenomic analysis showed that the relative abundance of Lactobacillus， Alistipes， and Akkermansia species was higher in the GP group than in the DM group. ConclusionG. pentaphyllum alcohol extract may improve glucose and lipid metabolism disorders in db/db mice by regulating the hepatic AMPK/PPARα pathway to suppress lipid deposition and alleviate hepatic steatosis， by inhibiting gluconeogenesis through the AMPK/PGC-1α and FoxO pathways to lower fasting blood glucose， and by increasing the abundance of beneficial gut bacteria such as Lactobacillus， Alistipes， and Akkermansia to restore gut microbiota balance.

Objective To compare the effects of CalliSpheres drug-eluting beads transcatheter arterial chemoembolization(DEB-TACE)and conventional TACE(c-TACE)on liver fibrosis and liver function in the treatment of primary hepatocellular carcinoma(HCC).Methods A total of 40 patients diagnosed with HCC at Xuzhou Municipal Cancer Hospital of China between October 2020 and October 2022 were enrolled in this study.According to therapeutic scheme,the patients were divided into DEB-TACE group(n=20)and c-TACE group(n=20).The preoperative,and postoperative 5-day and one-month hyaluronidase(HA),type Ⅲ procollagen peptide(P Ⅲ NP),type Ⅳ collagen(CⅣ)and laminin(LN),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),albumin(Alb),and prothrombin time(PT)were compared between the two groups.Results The technical success rate was 100％in both groups,and tumor staining completely disappeared immediately after TACE in all patients.The postoperative 5-day levels of HA,LN,P Ⅲ NP,and CⅣ in both groups were remarkably higher than the preoperative ones(P＜0.05).One month after TACE,HA level in the DEB-TACE group was prominently higher than its preoperative value(P＜0.05);HA and LN levels in the c-TACE group were obviously higher than their preoperative values(P＜0.05);and the HA and LN levels in c-TACE group were significantly higher than those in DEB-TACE group(P＜0.05).Five days after TACE,in the DEB-TACE group the AST and PT levels were higher than their preoperative values while the Alb level was lower than its preoperative value(P＜0.05);in the c-TACE group the ALT,AST,TBiL and PT were higher than their preoperative values while the Alb level was lower than its preoperative value(P＜0.05);the ALT and AST levels in the c-TACE group were strikingly higher than those in the DEB-TACE group while Alb level was strikingly lower than that in the DEB-TACE group(P＜0.05).Conclusion Both CalliSpheres DEB-TACE and c-TACE can aggravate liver fibrosis and cause liver function damage.However,the degree of liver fibrosis and liver function damage caused by CalliSpheres DEB-TACE is less than that caused by c-TACE.(J Intervent Radiol,2024,33:259-263)

Keratoconus is a progressive disease that seriously affects the eyesight of young people. Keratoconus often causes high myopia, irregular astigmatism, and some patients with advanced corneal scar, visual acuity significantly decreased. In the course of diagnosis and treatment of keratoconus, refractive reconstruction of keratoconus is the focus of clinical attention. After years of research and exploration, a variety of treatment methods in different stages of disease(non-progressive, progressive, advanced)for keratoconus patients refractive reconstruction, so that they can obtain good visual function. This paper mainly reviews the refractive reconstruction schemes of keratoconus in different periods, analyzes the advantages and disadvantages of various treatment schemes at home and abroad, and summarizes the characteristics of different treatment methods, with a view to providing theoretical reference and new treatment ideas for the diagnosis and treatment of keratoconus.

Objective:To explore the characteristics of latent profiles of health literacy in elderly patients with multiple chronic conditions (MCCs), and to analyze the impacts of the profiles on patients′ health promoting lifestyle, and to provide reference for developing intervention strategies.Methods:From July 2022 to May 2023, elderly patients with multiple chronic conditions in Nanfang Hospital, Southern Medical University were selected as the survey subjects by cross-sectional survey method. The General Information Questionnaire, All Aspects of Health Literacy Scale and Health Promoting Lifestyle Profile-Ⅱ were used for investigation. The latent profile analysis was conducted with the 11 entries of health literacy in elderly patients with MCCs as the explicit indicators. The difference of clinical data in potential profiles of health literacy were compared, and regression mixture model was implemented to analyze the impacts of different profiles on health promoting lifestyle of patients.Results:Totally 198 valid questionnaires [127 males and 71 females with 60-80(64.57 ± 4.60) years old] were collected, with the effective recovery rate of 94.3%. The latent profiles of health literacy in elderly patients with MCCs was divided into 3 profiles, high literacy and high efficiency in health information application group 51 cases (25.8%), moderate literacy and moderate efficiency in health information application group 87 cases (43.9%), low literacy and low efficiency in health information application group 60 cases (30.3%). Education level [high school or technical secondary school: OR(95% CI)=0.134(0.034-0.531), college degree or above: OR(95% CI)=0.056(0.005-0.670)], per capita monthly income of families [3 000-5 000yuan: OR(95% CI)=0.176(0.052-0.593), >5 000 yuan: OR(95% CI)=0.095(0.024-0.370)], years of illness [>5years: OR(95% CI)=0.204(0.053-0.787)], and number of co-occurring diseases [4-5kinds: OR(95% CI)=3.500(1.324-4.252)] were the influencing factors of high literacy and high efficiency in health information application group (all P<0.05). Per capita monthly income of families [3 000-5 000yuan: OR(95% CI)=0.336(0.150-0.752)] and years of illness[1-5years: OR(95% CI)=0.266(0.098-0.721)] were the influencing factors of moderate literacy and moderate efficiency in health information application group (all P<0.05). There were statistically significant difference in the total score of Health Promoting Lifestyle Profile-Ⅱ and the scores of each dimension among elderly patients with MCCs between 3 latent profiles ( F=32.12-81.04, all P<0.05). Conclusions:The health literacy of elderly patients with MCCs is significantly heterogeneous, and there are significant differences in health promoting lifestyle among the profiles. Medical staff should formulate personalized intervention strategies based on the classification characteristics of health literacy of MCCs elderly patients to improve their health promoting lifestyle.

Objective:To explore application research of intimacy enhancement therapy in the rehabilition of depression patients, and to provide reference for carrying out depression nursing care.Methods:This study was a randomized controlled trial. From September 2022 to September 2023, a total of 84 depression patients and spouse were selected by convenience sampling method and assigned to the experimental group and control group with 42 cases in each group using the random number table method from Nanfang Hospital, Southern Medical University. The control group applied with routine nursing, and the experimental group implemented intimacy enhancement therapy. Before and 8 weeks after intervention, Hamilton Depression Scale (HAMD-17), Hamilton Anxiety Scale (HAMA-17) and Symptom checklist-90 (SCL-90) were used for assessment.Results:Finally, 81 patients completed the study, including 39 in the experimental group, 13 males and 26 females, aged (36.18 ± 10.93) years old, and 42 in the control group, 17 males and 25 females, aged (38.76 ± 10.90) years old. Before intervention, there was no significant difference in HAMD-17, HAMA-17 and SCL-90 (all P>0.05). After 8 weeks of intervention, the scores of HAMD-17, HAMA-17 scores in the experimental group were (21.00 ± 4.49), (25.38 ± 5.16) points, which were lower than (23.76 ± 6.24), (28.48 ± 5.88) points in the control group; the scores of somatization, interpersonal sensitivity, compulsion, anxiety, depression, others, total SCL-90 in the experimental group were (1.25 ± 0.19), (0.69 ± 0.35), (1.40 ± 0.23), (1.17 ± 0.29), (1.18 ± 0.14), (1.22 ± 0.18), (119.69 ± 9.09) points, which were also lower than (1.82 ± 0.26), (1.53 ± 0.36), (1.69 ± 0.39), (1.88 ± 0.38), (1.73 ± 0.35), (1.31 ± 0.17), (146.19 ± 8.97) points of the control group, the differences were statistically significant ( t values were 2.05-13.20, all P<0.05). Conclusions:Intimacy enhancement therapy can effectively alleviate somatic symptoms and improve prognosis of patients with depression.

OBJECTIVE To investigate the effect of gene polymorphism on opioid-induced constipation. METHODS The target genes related to opioid-induced constipation were screened out through searching guidelines， databases and evidence-based medical data， and then 100 cancer pain patients who received opioid drugs for analgesia were included as the study subjects. According to whether there were adverse effects of constipation after medication or not， they were divided into test group and control group， with 50 cases in each group. The target gene was detected by PCR or fluorescence in situ hybridization. The SNPStats program was used to carry out Hardy-Weinberg balance test and correlation analysis between gene polymorphism and opioid-induced constipation. The multivariate Logistic regression analysis was used to explore the relevant predictive factors of opioid-induced constipation， and receiver operating characteristic （ROC） curve of subjects was drawn to analyze the effectiveness of each predictive factor in predicting opioid-induced constipation. RESULTS CYP2D6， CYP3A5*3， ABCB1 and OPRM1 were selected as target genes for detection. The results of genotype detection showed that the frequency distribution of CYP2D6 （rs1065852， rs1135822， rs16947， rs28371725， rs28371735）， CYP3A5*3 （058rs776746）， ABCB1 （062rs1045642）， OPRM1 （047rs1799971） alleles were consistent with Hardy-Weinbergbalance test. The correlation analysis results showed that the proportion of genotype GG and AG in CYP3A5*3 （058rs776746， 163.com A＞G） and genotype AA and AG in OPRM1 （047rs1799971， A＞G） of patients was significantly higher in test group than that in the control group （P＜0.05）. Multivariate Logistic regression analysis showed that medication duration， CYP3A5*3 and OPRM1 gene polymorphism could be used as predictors of opioid- induced constipation in patients （P＜0.05）. The ROC curve analysis results showed that the areas under the ROC curves for medication duration and CYP3A5*3， OPRM1 gene polymorphism were 0.648， 0.640 and 0.670， respectively， with the optimal cutoff values of 124.0， 0.5 and 0.5， respectively. CONCLUSIONS Genotype GG and AG in CYP3A5*3 （058rs776746，A＞G） and genotype AA and AG in OPRM1 （047rs1799971，A＞G） are associated with opioid-induced constipation， which are expected to become clinical predictors of opioid-induced constipation， and more attention should be paid to the occurrence of constipation in patients who have been taking opioids for a long time.

Objective:To investigate the influence of long-term wear of soft contact lenses on corneal transparency.Methods:A cross-sectional study was conducted.The corneal optical density of female myopic patients who planned to undergo corneal refractive surgery in Jinan Mingshui Eye Hospital from January 2018 to December 2020 was examined.The patients were divided into ≥2-<5 years group, ≥5-<10 years group, and ≥10 years group according to the duration of wearing contact lenses.Age- and sex-matched patients without wearing soft contact lenses were enrolled as a control group.There were 50 eyes from 50 cases in each group.The cornea was divided into 0-2, 2-6, 6-10, and 10-12 mm corneal vertex-centered annuli.The cornea over each annulus was divided into a superficial layer (≤120 μm from the outer surface of the cornea), a deep layer (≤60 μm from the inner surface of the cornea) and a central layer (between the superficial and deep layers). Measurements of the right eye were taken for analysis.The corneal optical density of different layers over different corneal ring regions was compared.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Jinan Mingshui Eye Hospital (No.2018-005). Written informed consent was obtained from each subject before any medical examination.Results:The corneal optical density tended to decrease as the wearing duration of corneal contact lens extended.The corneal optical density values of control group, ≥2-<5 years group, ≥5-<10 years group, and ≥10 years group were 18.51±1.79, 18.25±2.10, 18.16±1.89 and 17.83±1.65, respectively, showing no significant difference ( F=1.152, P=0.329). There was no significant difference in the corneal optical density of the superficial layer over 0-2, 2-6, and 6-10 mm annuli among the four groups ( F=2.077, 2.080, 2.229; all at P>0.05). There was a significant difference in the corneal optical density of the superficial layer over 10-12 mm annulus among the four groups ( F=5.016, P=0.002), and the corneal optical density of the superficial layer was greater in ≥5-<10 years group than in ≥2-<5 years, and greater in ≥10 years group than in control group, showing statistically significant differences (both at P<0.05). There were significant differences in the corneal optical density of the central layer over 0-2 and 6-10 mm annuli ( F=3.808, 2.813; both at P<0.05), and the corneal optical density of the central layer was lower in ≥10 years group than in control group, showing a statistically significant difference ( P<0.05). There were significant differences in the corneal optical density of the deep layer over 0-2, 2-6, 6-10 and 10-12 mm annuli ( F=5.485, 5.625, 3.398, 2.775; all at P<0.05). The optical density of the deep layer was lower in ≥5-<10 years than in control and ≥2-<5 years groups over 0-2, 2-6, and 10-12 mm annuli, lower in ≥5-<10 years group than in control group over the 6-10 annulus, and lower in ≥10 years group than in control group over 0-2, 2-6, and 6-10 mm annuli, and the differences were statistically significant (all at P<0.05). Conclusions:For women, the long-term wear of soft contact lenses for 5 years does not affect corneal transparency, and long-term wear for more than 5 years can cause a decrease in the transparency of the superficial peripheral cornea.

Precisely delivering combinational therapeutic agents has become a crucial challenge for anti-tumor treatment. In this study, a novel redox-responsive polymeric prodrug (molecular weight, MW: 93.5 kDa) was produced by reversible addition-fragmentation chain transfer (RAFT) polymerization. The amphiphilic block polymer-doxorubicin (DOX) prodrug was employed to deliver a hydrophobic photosensitizer (PS), chlorin e6 (Ce6), and the as-prepared nanoscale system [NPs(Ce6)] was investigated as a chemo-photodynamic anti-cancer agent. The glutathione (GSH)-cleavable disulfide bond was inserted into the backbone of the polymer for biodegradation inside tumor cells, and DOX conjugated onto the polymer with a disulfide bond was successfully released intracellularly. NPs(Ce6) released DOX and Ce6 with their original molecular structures and degraded into segments with low MWs of 41.2 kDa in the presence of GSH. NPs(Ce6) showed a chemo-photodynamic therapeutic effect to kill 4T1 murine breast cancer cells, which was confirmed from a collapsed cell morphology, a lifted level in the intracellular reactive oxygen species, a reduced viability and induced apoptosis. Moreover, ex vivo fluorescence images indicated that NPs(Ce6) retained in the tumor, and exhibited a remarkable in vivo anticancer efficacy. The combinational therapy showed a significantly increased tumor growth inhibition (TGI, 58.53%). Therefore, the redox-responsive, amphiphilic block polymeric prodrug could have a great potential as a chemo-photodynamic anti-cancer agent.