Keratoconus is a blinding corneal disease characterized by central or paracentral corneal thinning and conical ectasia, and usually happens in adolescence. Currently, the etiology of keratoconus is unclear. Multiple studies have identified an association between genetics, eye rubbing, allergic diseases, ultraviolet exposure and keratoconus. Recently, several studies identified that sex hormones also played important roles in the pathogenesis of keratoconus. The disturbance of sex hormones may increase the risk of occurrence and progress of keratoconus. This review aims to summarize the pathophysiological effects of sex hormones on the cornea, clarify the effects of sex hormones on keratoconus and its related inflammatory or immune mechanisms, and explore the role of sex hormones in the early diagnosis and treatment of keratoconus, providing reference and help for clinical work.

OBJECTIVE To study the pharmacokinetics and tissue distribution of cannabidiol（CBD）-cholesterol succinate monoester-g-carboxymethyl chitosan （CCMC） nano-micelles in rats， and to evaluate its anti-inflammatory effect. METHODS CBD- CCMC nano-micelles were prepared by dialysis method and the properties were characterized. SD rats were divided into CBD group and CBD-CCMC nano-micelles group with 6 rats in each group. The rats were given 100 mg/kg CBD and CBD-CCMC nano- micelle by intragastric administration， respectively （based on the CBD load）. Blood was collected from the posterior ophthalmic venous plexus at 0.5， 1， 1.33， 1.5， 1.75， 2， 4， 8， 24， 48 h after administration. The heart， liver， spleen， lung， kidney and muscle tissues of rats were separated at 0.25， 1.5， 10 and 24 h after administration of CBD and CBD-CCMC nano-micelle with the same dose. The drug content in plasma and tissues was determined， the pharmacokinetic parameters were calculated， and the tissue distribution was analyzed. The inflammatory model of Caco-2 cells was induced by lipopolysaccharide， after 24 h of treatment with 5， 10， and 15 µg/mL CBD and CBD-CCMC nanomicelles （based on loaded CBD）， its anti-inflammatory activity was investigated by measuring cell viability， transepithelial electrical resistance （TEER） and inflammatory cytokines IL-1β， IL-8 and TNF-α. RESULTS The prepared CBD- CCMC nano-micelles had a particle size of （230.6±1.8） nm， a polydispersity index of 0.170±0.053， a Zeta potential of （－13.5± 1.2） mV， an encapsulation rate of （86.35±0.56）% and a drug loading of （9.18±0.32）%， respectively； the solubility was 68.240 μg/mL. The pharmacokinetic results showed that the AUC0-48 h， AUC0-∞， half-life time and peak concentration of CBD-CCMC nano- micelle group were significantly increased/extended compared with CBD group （P＜0.05 or P＜0.01）. The results of the tissue distribution study showed that at the same time point， the drug distribution concentration of CBD-CCMC nanomicelles in the rat tissue was higher than that in the CBD group. Research on anti-inflammatory effects shows that compared with CBD of the same mass concentration, CBD-CCMC nano-micelles can significantly increase cell viability （P＜0.05 or P＜0.01）， enhance TEER， and reduce the levels of IL-8， IL-1β and TNF-α in cells （P＜0.01）， and the secretion levels of inflammatory cytokines IL-8， IL-1β and TNF- α were significantly decreased （P＜0.01）. CONCLUSIONS CBD-CCMC nano-micelles can increase the plasma concentration and tissue distribution concentration of CBD， and improve anti-inflammatory activity of CBD.

Objective:To investigate the repeatability of corneal topographic parameters with the Pentacam HR in patients with keratoconus of different severity.Methods:A diagnostic test study was performed.A total of 120 eyes from 98 patients with subclinical keratoconus or keratoconus were enrolled at Henan Eye Hospital from January 2019 to March 2022.The patients were divided into subclinical keratoconus group, mild keratoconus group, moderate keratoconus group and severe keratoconus group, with 30 eyes in each group.An additional 30 eyes of 30 subjects undergoing refractive surgery were selected as a control group.Three consecutive Pentacam HR measurements were performed by the same clinician.The recordings included a total of 53 parameters in anterior corneal surface, posterior corneal surface, thickness, composite index, and corneal densitometry.The within-subject standard deviation (Sw), repeatability limit ( r) and tolerance index (TI) were calculated to evaluate the repeatability of the parameters between different groups.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[5]).All subjects were informed of the purpose and significance of the study and signed an informed consent form before enrollment. Results:Compared with the control group, the TI of the subclinical, mild, moderate and severe keratoconus groups were 54.71%(29/53), 66.04%(35/53), 90.57%(48/53) and 94.34%(50/53), respectively, higher than 0.31.The steep keratometry (Ks), the maximum keratometry (Kmax) of the anterior corneal surface, the anterior corneal radius of curvature, the flat keratometry (Kf) of the posterior corneal surface, the posterior corneal radius of curvature (PRC), the thinnest corneal thickness (TCT), the average densitometry for the anterior 120 μm in the 0-2 mm area (A.0-2 mm), average densitometry for the anterior 120 μm in the 2-6 mm area (A.2-6 mm), average densitometry for the central tissue in the 0-2 mm area (C.2-6 mm), average densitometry for the total cornea in the 0-2 mm area (T.0-2 mm) and average densitometry for the total cornea in the 2-6 mm area (T.2-6 mm) showed good repeatability in the subclinical and mild keratoconus groups (TI<0.31).Kmax Zonal Mean 3 mm, posterior corneal surface mean keratometry, central keratoconus index showed good repeatability in subclinical, mild and moderate keratoconus groups.Kmax Zonal Mean 4 mm and Kmax Zonal Mean 5 mm showed good repeatability in all groups (TI<0.31).Conclusions:For patients with subclinical and mild keratoconus, Kf of the posterior corneal surface, PRC and TCT are recommended to monitor disease progression.To monitor the condition of patients with moderate and severe keratoconus, we may focus on the detection of Kmax Zonal Mean 4 mm and Kmax Zonal Mean 5 mm.

Objective To analyze the causal relationship between statins and type 1 or type 2 diabetes mellitus by using Mendelian randomization(MR).Methods Based on the collected data of genome-wide association studies(GWAS),single nucleotide polymorphism(SNP),which were independent of each other and highly correlated with statins and diabetes mellitus,were selected as tool variables.MR-Egger regression,weighted median,inverse variance weighting(IVW),simple mode and weighted mode were used for two-sample MR analyses to evaluate the causal relationship between statins and type 1 or type 2 diabetes respectively,and heterogeneity tests,multiplicity analyses,and sensitivity analysis to evaluate the reliability of the study.Results A total of 78 SNPs independently associated with statins were included as tool variables in this study at the genome-wide significance level(P＜5×10-8).The results of IVW analysis showed that statins were causally associated with an increased risk of type 1 diabetes mellitus(OR=1.524,95％CI 1.077 to 2.157,P=0.017),and there was also a causal relationship between statins and the increased risk of type 2 diabetes(OR=1.261,95％CI 1.165 to 1.366,P＜0.001).The results were not affected by multiplicity and heterogeneity,and the reliability of the results was verified by sensitivity analysis.Conclusion Statins may be a risk factor for increasing the risk of type 1 or type 2 diabetes.However,further studies with larger sample sizes of GWAS data are still needed to verify the causal association.

Drug use monitoring and evaluation play a key role in promoting drugs to return to clinical value,optimizing the basic medicine system,and improving the drug supply guarantee system.In order to promote the implementation of drug use monitoring and evaluation in medical institutions,the Pharmaceutical Affairs Committee of the Chinese Hospital Association led the efforts of organizing relevant domestic experts to follow the group standard development process.It successfully formulated the group standard of Drug Use Monitoring and Evaluation through the steps of problem sorting,framework construction,evidence collection,draft writing,opinion consultation,and standard formation.This article introduces the standard formulation process in detail,and explains and analyzes the content of the standard,aiming to help readers better understand the connotation of drug use monitoring and evaluation,and provide practical guidance.

Objective:To investigate the effect of high-frequency repetitive transcranial magnetic stimulation combined with sertraline on depressive symptoms and self-injurious behaviors in adolescents with depression and non-suicidal self-injury.Methods:This study was a prospective study. A total of 112 adolescent patients with depression and non-suicidal self-injury who received treatment at the Third Hospital of Quzhou from January 2021 to September 2023 were included in this study. These patients were divided into a control group and a study group, with 56 patients per group, using the random digital table method. The control group was treated with sertraline, while the study group was treated with high-frequency repetitive transcranial magnetic stimulation combined with sertraline. The depression scores [assessed using the 24-item Hamilton Depression Scale (HAMD-24) and the Self-Rating Depression Scale (SDS)], self-injury status, and inflammatory factor levels (tumor necrosis factor-α, interleukin-10, and interleukin-1β levels) were compared before and after the intervention.Results:Before intervention, there were no statistically significant differences in HAMD-24 scores and SDS scores between the two groups (both P > 0.05). After intervention, both HAMD-24 scores and SDS scores decreased significantly in both groups (both P < 0.05). Additionally, the HAMD-24 scores [(13.46 ± 3.98) points] and SDS scores [(50.28 ± 5.13) points] in the study group were significantly lower than those in the control group [(19.89 ± 4.23) points, (71.62 ± 6.88) points, t = -8.28, -18.61, both P < 0.05]. Before intervention, there were no statistically significant differences in the number of self-injury incidents and self-injurious behavior scores between the two groups (both P > 0.05). After intervention, the number of self-injury incidents and the score of self-injurious behaviors significantly decreased in the study group compared with before intervention (both P < 0.05). After intervention, the number of self-injury incidents in the control group was decreased compared with before intervention ( P < 0.05), while the score of self-injurious behaviors did not differ significantly compared with before intervention ( P > 0.05). After intervention, the number of self-injury incidents [(2.15 ± 1.06) times] and the score of self-injurious behaviors [(2.41 ± 0.65) points] in the study group were significantly lower than those in the control group [5.43 ± 3.61) times, (12.04 ± 3.01) points, t = -7.78, -23.40, both P < 0.05]. Before intervention, there were no statistically significant differences in interleukin-1β, tumor necrosis factor-α, and interleukin-10 levels between the two groups (all P > 0.05). After intervention, interleukin-1β and tumor necrosis factor-α levels in the study group were significantly lower than those before intervention (both P < 0.05), while interleukin-10 levels in the study group were significantly higher than those before intervention ( P < 0.05). There were no statistically significant differences in the levels of interleukin-1β, tumor necrosis factor-α, and interleukin-10 between the pre- and post-intervention measurements in the control group (all P > 0.05). After intervention, interleukin-1β levels [(57.15 ± 6.33) ng/L] and tumor necrosis factor-α levels [(13.87 ± 5.91) ng/L] in the study group were significantly lower than those in the control group [(73.61 ± 8.52) ng/L, (17.12 ± 5.28) ng/L], while interleukin-10 levels [(1.62 ± 0.66) ng/L] were significantly higher than those in the control group [(1.19 ± 0.63) ng/L, t = -11.60, 3.53, -3.07, all P < 0.05]. Conclusion:High-frequency repetitive transcranial magnetic stimulation combined with sertraline can significantly reduce depressive symptoms and self-injurious behaviors in adolescents with depression and non-suicidal self-injury. The reason may be due to the decrease in inflammatory factor levels in patients.

Objective:To investigate the effect of high-frequency repetitive transcranial magnetic stimulation combined with fluvoxamine treatment on improving depression, impulsivity, and self-injury levels in adolescent patients with depression.Methods:A total of 124 adolescent patients with depression who received treatment at the Department of Psychiatry, The Third Hospital of Quzhou, China from January 2022 to November 2023 were included in this study. The patients were randomly divided into a control group and an observation group, with 62 patients per group, using the random number table method. Patients in the control group received treatment with fluvoxamine, while patients in the observation group underwent high-frequency repetitive transcranial magnetic stimulation and treatment with fluvoxamine. Clinical efficacy and the scores of the Hamilton Depression Scale, Hamilton Anxiety Scale, the Barratt Impulsiveness Scale-ll revised version, and the Non-Suicidal Self-Injury Assessment Tool revised version were compared between the two groups.Results:The total response rate in the observation group was 90.32% (56/62), which was significantly higher than that in the control group [72.58% (45/62), χ2 = 6.46, P < 0.05]. After treatment, scores of the Hamilton Depression Scale and Hamilton Anxiety Scale in the observation group were (12.08 ± 1.97) points and (11.58 ± 1.59) points, respectively, which were significantly lower than those in the control group [(16.42 ± 2.33) points, (14.42 ± 1.94) points, t = -8.28, -18.61, both P < 0.05]. After treatment, the scores of the Barratt Impulsiveness Scale-ll revised version and Non-Suicidal Self-Injury Assessment Tool revised version in the observation group were significantly lower than those in the control group [(28.25 ± 3.91) points, (9.23 ± 2.12) points, t = 5.42, 9.44, both P < 0.05]. Conclusion:High-frequency repetitive transcranial magnetic stimulation combined with fluvoxamine treatment can significantly reduce depressive symptoms, impulsivity, and self-injury levels in adolescent patients with depression.

OBJECTIVE: To explore the clinical and genetic characteristics of two children with Williams-Beuren syndrome (WBS). METHODS: Two children who had presented at the Department of Pediatrics, General Hospital of Ningxia Medical University respectively on January 26 and March 18, 2021 were selected as the study subjects. Clinical data and results of genetic testing of the two patients were analyzed. RESULTS: Both children had featured developmental delay, characteristic facies and cardiovascular malformation. Child 1 also had subclinical hypothyroidism, whilst child 2 had occurrence of epilepsy. Genetic testing revealed that child 1 has harbored a 1.54 Mb deletion in the 7q11.23 region, whilst child 2 has a 1.53 Mb deletion in the same region, in addition with a c.158G>A variant of the ATP1A1 gene and a c.12181A>G variant of the KMT2C gene. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.158G>A and c.12181A>G variants were rated as variants of unknown significance (PM1+PM2_Supporting+PP2+PP3；PM2_Supporting). CONCLUSION Both children had characteristic features of WBS, for which deletions of the 7q11.23 region may be accountable. For children manifesting developmental delay, facial dysmorphism and cardiovascular malformations, the diagnosis of WBS should be suspected, and genetic testing should be recommended to confirm the diagnosis.
Child ; Humans ; Williams Syndrome/diagnosis* ; Genetic Testing ; Facies ; Epilepsy/genetics* ; Chromosomes, Human, Pair 7/genetics* ; Chromosome Deletion

OBJECTIVE To develop a whole-process intelligent model of pharmaceutical care for peritoneal dialysis （PD） patients， and to provide a reference for clinical pharmacists to provide standardized PD pharmaceutical care. METHODS The pharmaceutical care mode of PD patients at home and abroad was investigated and analyzed. Based on the actual situation of the First Affiliated Hospital of Soochow University （hereinafter referred to as “our hospital”）， with “home→PD center outpatient→ inpatient department” as the main node， the recycling process of medication reconciliation was optimized. The whole-process intelligent pharmaceutical care model of PD was illustrated by improving the Chinese version of the drug-related problems （DRPs） classification tool， developing the corresponding pharmaceutical care process， and presenting specific cases. RESULTS Based on the medication therapy management （MTM） platform， our hospital had built a closed-loop PD whole-process intelligent pharmaceutical care model of “in-hospital pharmaceutical care （building document）-PD outpatient MTM-home pharmaceutical care （online App management）”. A “double cycle” workflow of “admission→discharge→outpatient” medication reconciliation cycle and “discovery-analysis-intervention-follow-up-record-evaluation” DRPs cycle was formed. CONCLUSIONS The establishment of the whole-process intelligent pharmaceutical care model for PD in our hospital provides experience for standardizing pharmaceutical care for PD patients， and can reduce DRPs.

ObjectiveTo investigate the expression of lysophosphatidic acid （LPA） in patients with liver cancer， as well as its influence on malignant biological behavior of liver cancer and related regulatory mechanism. MethodsFrom January 2016 to December 2022， 26 patients with liver cancer， 28 patients with liver cirrhosis， and 28 individuals undergoing physical examination were enrolled. ELISIA was used to measure the content of LPA in plasma and peritoneal effusion of the patients with liver cancer or liver cirrhosis accompanied by peritoneal effusion， and the content of LPA was measured in plasma of the normal population at the same time， so as to clarify the difference in the expression of LPA in different populations， such as the patients with liver cancer and those with liver cirrhosis. MTT cell proliferation assay and cell migration assay were used to observe the influence of LPA and its inhibitor pertussis toxin （PTX） on the proliferation， migration， and invasion of SMMC7721 cells. In order to investigate the effect of LPA on the expression of RhoA and its upstream and downstream molecules FAK and P53 after binding to its receptor， qPCR and Western blot were used to observe the effect of LPA on the mRNA and protein expression levels of P53， FAK， and RhoA in SMMC7721 cells. A one-way analysis of variance was used for comparison of the means of continuous data between multiple groups， and the SNK-q test was used for comparison between two groups. ResultsCompared with the patients with liver cirrhosis， the patients with liver cancer had a significantly higher concentration of LPA in plasma （4.99±0.55 μmol/L vs 2.63±0.43 μmol/L， P<0.05） and peritoneal effusion （5.19±0.63 μmol/L vs 2.91±0.46 μmol/L， P<0.05）， and the patients with liver cancer also had a significantly higher level of plasma LPA than the normal population （4.99±0.55 μmol/L vs 1.61±0.39 μmol/L， P<0.05）. The cell proliferation assay showed that LPA significantly promoted the proliferation of SMMC7721 cells， and cell proliferation rate increased with the increase in dose and time； in particular， the middle-and high-dose groups had a significantly higher proliferation rate than the control group （P<0.05）. PTX inhibited the proliferative capacity of SMMC7721 cells in a time-dependent manner， and there was a significant difference between the groups （P<0.05）. The proliferation rate of the 72-hour high-dose LPA group was 3.6 times that of the control group， while the proliferation rate of the PTX group was 0.6 times that of the control group； the proliferation rate of the 72-hour high-dose LPA+PTX group was 1.2 times that of the control group. In addition， LPA increased the migration ability of hepatoma cells， while PTX inhibited their migration， in a time-dependent manner， and there was a significant difference between the groups （P<0.05）. The migration rate of the 72-hour high-dose LPA group was 3.09 times that of the control group， while the migration rate of the PTX group was 0.4 times that of the control group； the migration rate of the 72-hour high-dose LPA+PTX group was 0.99 times that of the control group. qPCR and Western blot showed that there were significant reductions in the mRNA and protein expression levels of P53 in SMMC7721 cells after LPA treatment， while there were significant increases in the mRNA and protein expression levels of FAK and RhoA； there was a significant difference between the LPA group and the control group （P<0.05）. ConclusionThere is an abnormal increase in the expression of LPA in patients with liver cancer， and LPA can promote the proliferation of liver cancer cells and increase their migration ability. At the same time， LPA changes the expression levels of P53， FAK， and RhoA， which may be associated with the promotion of tumor development and progression by LPA.