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.

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 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.

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.

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.

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

Objective:To investigate the clinical characteristics of patients with keratoconus, and to explore the factors influencing keratoconus severity.Methods:A cross-sectional study was performed.A total of 908 patients (1 476 eyes) with primary keratoconus were enrolled in Henan Eye Hospital from January 2019 to December 2021.The medical history data of patients were collected by face-to-face questionnaire survey.Refractive parameters were measured by subjective optometry.Intraocular pressure (IOP) was measured by a non-contact tonometer, and corrected IOP was calculated by Dresden formula.Corneal topography parameters was obtained using Pentacam HR.The subgroup analysis of clinical characteristics of all patients was performed by age (<21 years, 21~<31 years, ≥31 years) and gender.Disease severity was graded based on steep keratometry (Ks), namely mild (Ks<48 D), moderate (48 D≤Ks<55 D) and severe (Ks≥55 D). The influencing factors of disease severity in keratoconus were analyzed by ordered Logistic regression.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[5]). All subjects or guardians were informed of the purpose and significance of the study and written informed consent was obtained.Results:Of the 908 patients, 622 were with bilateral keratoconus and 286 were with unilateral keratoconus.The median age of onset was 20(17, 26) years, and the median age of diagnosis was 21(18, 27) years.The ratio of males to females was 3.05∶1.There were 9.80%(89/908) of the patients having a history of allergy, 25.55%(232/908) having a history of other systemic diseases, and 1.98%(18/908) having a family history of keratoconus.Of the 1 476 affected eyes, 27.57%(407/1 476) were diagnosed as severe keratoconus, and 61.94%(568/917) had a history of eye rubbing.The medians of sphericity, cylindricity, IOP, corrected IOP, Ks, thinnest corneal thickness (TCT), anterior corneal surface elevation (AE) and posterior corneal surface elevation (PE) were -4.00(-7.00, -1.75)D, -3.50(-6.00, -1.50)D, 12.00(10.30, 13.80)mmHg, 15.40(13.60, 17.00)mmHg, 49.85(46.40, 54.90)D, 460.00(425.00, 490.00)μm, 21.00(13.00, 34.75)μm, 51.00(33.00, 75.00)μm, respectively.The spherical refraction, IOP and corrected IOP were lower and the cylindrical refraction was higher in patients at age <21 years than in patients at age 21~<31 years, and the TCT of patients at age <21 years was higher than that at age ≥31 years, and the differences were statistically significant (all at P<0.05). Compared with female patients, male patients had younger onset age, lower spherical refraction, IOP and corrected IOP, as well as higher cylindrical refraction, AE and PE, showing statistically significant differences (all at P<0.05). The spherical refraction and IOP of male patients were lower than those of female patients at age <21 years, and the cylindrical refraction was higher in males than in females among the patients at age 21~<31 years, and the differences were statistically significant (both at P<0.05). Among the patients with onset age <21 years and diagnosis age <21 years, the ratio of males to females in patients with severe keratoconus was higher than those with mild and moderate disease, and the difference was statistically significant (both at P<0.05). Older age of onset was a protective factor for disease severity in keratoconus (odds ratio=0.981, 95% confidence interval: 0.963~0.999). Conclusions:The younger the onset age of keratoconus patients, the more severe the disease.Among the patients with severe keratoconus, there were more male patients, and males have a younger onset age and severer conditions.It is suggested that early screening of keratoconus in children and adolescents should be strengthened in clinical work, and more active prevention and treatment measures should be taken for younger patients, especially males.

Leucine-rich alpha-2 glycoprotein 1 (LRG1) is a highly conserved member of the family of leucine-rich repeat (LRR) proteins. LRG1 has been reported to be closely related to the occurrence and development of malignant tumors. Recent studies have shown that LRG1 is abnormally expressed in many digestive system tumors, including esophageal cancer, gastric cancer, liver cancer, pancreatic cancer, and colorectal cancer. LRG1 has also been reported to be closely related to tumor cell proliferation, invasion, migration, apoptosis, and poor prognosis. This paper reviews the research progress of LRG1 in many digestive system tumors, providing new ideas for LRG1-based anti-tumor treatment.