ObjectiveTo evaluate the effect of sex on phenotypic stability in mouse models of chemotherapy-induced alopecia (CIA) induced by cyclophosphamide (CYP) or paclitaxel (PTX), and to explore potential mechanisms underlying phenotypic heterogeneity in female mice. MethodsTwenty-eight wild-type specific pathogen-free (SPF) C57BL/6J mice (half male and half female) aged 6-8 weeks were selected for synchronous back hair removal. On the 9th day after hair removal (T0), the mice were randomly divided into a wild-type female CYP group, a wild-type male CYP group, a female negative control group and a male negative control group. Mice in the CYP groups were intraperitoneally injected with a single dose of 120 mg/kg CYP, and mice in the negative control groups were intraperitoneally injected with the same volume of normal saline. Subsequently, the phenotypic changes of the CIA model induced by CYP were continuously observed and photographed. Eleven 6-week-old SPF female C57BL/6J mice underwent bilateral ovariectomy (OVX group). Following successful surgery, these mice and five XY (Sry⁻) mice bred from Four Core Genotypes breeding stock were used to establish the chemotherapy-induced alopecia (CIA) model using the same protocol. Serum was collected from mice in the OVX group, wild-type female CYP group, and wild-type male CYP group on T7 after CYP administration for steroid hormone analysis by mass spectrometry to evaluate the effects of gonadal estrogen and sex chromosome background changes on the stability of the CYP-induced female alopecic phenotype. Finally, twenty SPF C57BL/6J mice aged 6-8 weeks (half male and half female) were randomly divided into a PTX low-dose group and a PTX high-dose group. On the 9th day after simultaneous hair removal, PTX was injected intraperitoneally at a single dose of 80 mg/kg or 120 mg/kg, respectively. Mice from the PTX low-dose group and the PTX high-dose group were continuously observed and photographed to compare the intra-group consistency of the phenotypes of female and male mice. Six SPF C57BL/6J mice (half male and half female) aged 6-8 weeks were used to repeat the construction method of the PTX low-dose group, and the hair follicle histological examination was performed at T0, T4, T7, T14 and T21, respectively, to observe the damage caused by PTX to hair follicle regeneration. ResultsThe phenotypes of CYP-induced male CIA mice are stable and reproducible. There are obvious individual differences in the alopecia phenotype in the CYP-induced female CIA model mice, which may be mainly caused by the differences in the relevant estrogens in the estrous cycle. The difference between OVX+CYP group and XY (Sry⁻) +CYP group disappeared, suggesting that ovarian-derived hormones and XY (Sry⁻) sex chromosome background may be involved in the formation of phenotypic heterogeneity of CYP-induced alopecia in female mice. The mice in the high-dose PTX group and the low-dose PTX group showed a relatively consistent alopecia and regrowth process, and there was no significant sex difference. ConclusionCYP-induced CIA is strongly influenced by sex, and ovariectomy or alteration of the sex chromosome background can improve the consistency of CYP-induced alopecic phenotypes in female mice. PTX-induced CIA shows good phenotypic consistency in both female and male mice, indicating broad applicability across sexes. Taken together, the choice of animal sex in CIA model construction, mechanistic studies, and evaluation of anti-alopecia interventions should take into account the type of chemotherapeutic agent, the study objective, and the required degree of phenotypic stability. Sex should therefore be considered an important variable in model standardization and interpretation of experimental findings.

Objective Patients with lung cancer often experience interrelated symptoms such as fatigue, pain, and sleep disturbances during chemotherapy, forming a core symptom cluster that significantly impacts daily functioning, treatment experience, and quality of life. Currently, evidence on non-pharmacological management of this core symptom cluster is scattered, and there is a lack of standardized, patient- and caregiver-friendly guidance tools that are easy to understand and implement. This patient guideline aims to provide decision support for self-management of the core symptom cluster in patients undergoing chemotherapy for lung cancer. Methods Guided by evidence-based methodology, qualitative interviews and on-site questionnaire surveys were conducted to identify the health-related needs of stakeholders. Domestic and international guideline websites, relevant professional association websites, and comprehensive databases were systematically searched according to the inclusion and exclusion criteria. The included literature was evaluated for quality, and recommendations were extracted, integrated, and graded to form a summary of the best evidence. Based on the identified health issues and evidence summary, preliminary recommendations for the patient guideline were developed. The recommendations were then revised through two rounds of Delphi expert consultation, and consensus was reached on the strength of recommendations, forming the final version of the patient guideline. Results The patient guideline covered four major sections: screening and assessment of core symptom clusters, daily management, intervention measures, and timing of referral. The core content included nine aspects: screening of core symptom clusters, assessment, lifestyle habits, dietary interventions, sleep environment, exercise interventions, psychological interventions, Traditional Chinese Medicine interventions, and referral indications. In total, the guidelines addressed 16 health issues and provided 25 recommendations. Conclusion The development process of this patient guideline is rigorous and fully considered the needs of patients. Expert review concludes that the recommendations are highly feasible and appropriate.

Objective: To investigate the distribution of pupil diameter and its association with myopia in school age children, providing ideas into the mechanisms of the role of pupil diameter in the onset and development of myopia. Methods: Adopting a combination of stratified cluster random sampling and convenience sampling method, 3 839 children from six schools in Shandong Province were included in September 2021. Pupil diameters distribution was analyzed by age, sex, and myopic status. Pearson correlation analysis was used to assess the relationship between pupil diameter and cycloplegic spherical equivalent (SE), as well as axial length (AL) and other variables. Propensity score matching (PSM) was applied to match myopic and non myopic children at a 1∶1 ratio based on age and sex. A generalized linear model (GLM) was constructed with pupil diameter as the dependent variable to identify independent factors influencing pupil size and its association with myopia. Results: The mean pupil diameter of school age children was (5.77±0.80)mm. Pupil diameter exhibited a significant increasing trend with age ( F =49.34， P trend ＜ 0.01). Myopic children had a significantly larger mean pupil diameter [(6.10±0.73)mm] compared to non myopic children [(5.62±0.79)mm] with a statistically significant difference( t=18.10, P <0.01). Multivariable GLM analysis, adjusted for age, amplitude of accommodation, and uncorrected visual acuity, revealed a negative correlation between pupil diameter and cycloplegic SE (before PSM: β =-0.089, after PSM: β =-0.063, both P ＜0.01). Conclusions Myopic school age children exhibite larger pupil diameters than their non myopic counterparts. Pupil diameter may serve as a potential indicator for monitoring myopia development in school age children.

OBJECTIVES: This study aims to investigate factors influencing dental arch development in patients aged 0-6 years with cleft palate after Sommerlad-Furlow (SF) palatoplasty. METHODS: A total of 183 patients who underwent primary SF repair for cleft lip and palate before 18 months of age were included. Follow-ups were conducted at different ages, and digital dental casts of the maxillary dental arch were obtained using 3-matic Research 12.0 software. The length and width of the dental arch and palate were measured to explore developmental changes in the maxillary dental arch of the patients after the procedure. The study also investigated the influence of gender, age, cleft palate type, and relaxation incision on maxillary dental arch development. RESULTS: After SF, maxillary dental arch measurements showed statistically significant differences between children aged 0-2 years and those aged 3-6 years (P<0.05). However, no statistically significant differences were observed among different age groups within the 3-6 years range. Statistically significant differences were detected between males and females, with males having greater width of the posterior dental arch and palate (P=0.001) and shorter length of the anterior dental arch and entire dental arch (P<0.05). The unilateral cleft lip and palate group had shorter dental arch length (P<0.01) and wider posterior palate (P<0.01) than the cleft palate only group. Maxillary dental arch measurements had no statistically significant differences between groups with or without a relaxing incision. CONCLUSIONS Gender and age influence the width of the maxillary dental arch in children aged 0-6 years after SF, while age and cleft palate type affect dental arch length.
Humans ; Child, Preschool ; Male ; Cleft Palate/surgery* ; Female ; Child ; Infant ; Dental Arch/growth & development* ; Maxilla/growth & development* ; Cleft Lip/surgery* ; Age Factors ; Sex Factors ; Palate/surgery* ; Infant, Newborn

Objective To explore the predictive value of combined detection of serum CXC chemokine lig-and 12(CXCL12),caspase-cleaved cytokeratin 18(CCCK-18)and matrix metalloproteinase-9(MMP-9)for short-term poor prognosis in patients with acute hemorrhagic stroke.Methods A total of 138 patients with a-cute hemorrhagic stroke admitted to a hospital from October 2021 to March 2023 were selected as the study objects.Serum CXCL12,CCCK-18 and MMP-9 levels were detected after admission and before treatment.Pa-tients were followed up for 6 months after treatment and were divided into good prognosis group and poor prognosis group according to the modified Rankin scale score.Clinical data and serum CXCL12,CCCK-18 and MMP-9 levels of the two groups were compared to analyze the factors affecting the short-term poor prognosis of patients with acute hemorrhagic stroke.Receiver operating characteristic(ROC)curve was drawn to evalu-ate the predictive value of single and combined detection of serum CXCL12,CCCK-18 and MMP-9 in patients with acute hemorrhagic stroke.Results Among 138 patients,there were 52 cases in the poor prognosis group and 86 cases in the good prognosis group,and the poor prognosis rate was 37.68%.Serum CXCL12,CCCK-18 and MMP-9 levels,age,blood loss at admission,National Institutes of Health Stroke Scale(NIHSS)score at admission,systolic blood pressure and diastolic blood pressure at admission in the poor prognosis group were higher than those in the good prognosis group.The score of Glasgow Coma Scale(GCS)at admission was lower than that of good prognosis group,and the difference was statistically significant(P<0.05).Multivari-ate Logistic regression analysis showed that high level of serum CXCL12,high level of CCCK-18,high level of MMP-9,older age,large amount of blood loss upon admission,high NIHSS score and high systolic blood pres-sure were all risk factors for short-term poor prognosis of acute hemorrhagic stroke(P<0.05).High GCS score on admission was a protective factor(P<0.05).ROC curve analysis showed that the area under the combined prediction curve of serum CXCL12,CCCK-18 and MMP-9 was higher than that of the single and pairwise combined prediction of each index(P<0.05).Conclusion The combined detection of serum CX-CL12,CCCK-18 and MMP-9 has a good value in predicting the short-term poor prognosis of patients with a-cute hemorrhagic stroke.

[Objective]To explore the etiology,pathogenesis,syndrome and treatment of coronary heart disease with depression based on the theory of"the pathways of spirit".[Methods]Starting from the theory of"the pathways of spirit",the relationships among insufficient control of spirit,obstructed the pathways of spirit and impaired heart-spirit functioning in coronary heart disease with depression were analyzed,and the treatment principles at different stages were summarized.[Results]The evolution of coronary heart disease with depression is based on the deficiency of Qi and blood and the insufficient control of spirit.At this stage,Guipi Decoction,Guizhi Longgu Muli Decoction and Jiji Decoction should be used to supplement Qi and blood.The root cause of coronary heart disease with depression is the combination of blood stasis and toxin,which leads to the obstruction of the pathways of spirit.At this stage,Xuefu Zhuyu Decoction or Simiao Yong'an Decoction should be used to dissipate blood stasis and detoxing,combined with large dosage of Astragalus membranaceus to strengthen the healthy Qi without retaining pathogens.The important reason for the deterioration of coronary heart disease with depression is stagnation of Qi which causes impaired heart-spirit functioning.At the obvious stage of Qi stagnation,modified prescriptions such as Bupleurum based formulas and Yueju Pill should be flexibly applied to promote Qi circulation and relieve depression,combined with acupuncture in order to prevent the deterioration of the disease.[Conclusion]"The pathways of spirit"is the way of heart spirit interaction,and communication and coordination between the heart and other organs.Insufficient control of spirit,obstructed pathways of spirit,and impaired heart-spirit functioning are important pathogenesis for the occurrence and development of coronary heart disease with depression.Based on the theory of"the pathways of spirit",it helps to understand the disease evolution process of coronary heart disease with depression,improve the staged diagnosis and treatment rules and specific prescriptions for coronary heart disease with depression.

BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.

N6-methyladenosine(m6A)methylation modification is the most common post-transcriptional modification in eukaryotic RNA and plays an important role in RNA metabolism,immune cell stability,and immunomodulation.Systemic lupus erythematosus(SLE)is a diffuse,systemic autoimmune disease caused by the binding of autoantibodies to corresponding autoimmune antigens to form immune complex deposits.The pathogenesis of SLE is complex.With the continuous deepening of research,it has been discovered in recent years that m6A methylation modification can participate in the occurrence of SLE by regulating immune cells and promote the development of SLE from aspects such as oxidative stress and inflammatory response.This article reviews the research progress on the three proteins modified by m6A methylation and their relationship with the pathogenesis of SLE.

Objective:To analyze the correlation between near work, screen time, outdoor time and myopia in children based on objective monitoring technology and to explore the influencing factors related to myopia in children.Methods:A cross-sectional study was conducted.From October 2022 to March 2023, the purposive sampling method was used to select 596 children in Grade 2 and Grade 3 from two primary schools in Shandong Province as study subjects.Eye-Monitor technology of eye-use behavior based on artificial intelligence was used to quantify parameters of near work, screen time and outdoor time.The eye-use behavior parameters were compared within each subject and between non-myopic and myopic children on weekdays and weekends.A multivariate binary logistic regression model was constructed to analyze the influencing factors related to myopia.The study protocol was approved by the Medical Ethics Committee of the Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine (No.HEC-HY-2022023KY).Written informed consent was obtained from the legal guardian of each subject.Results:For each subject, the proportion of near work time on weekdays was greater than on weekends, the proportion of time spent looking at cell phones, computer screens, and outdoor activities was smaller, the duration of single continuous near eye use was longer, the tilt angle of the head in sitting position was greater, and the light intensity was stronger, showing statistically significant differences ( t=19.427, -9.964, -5.916, -10.470, 2.211, 2.898, 15.061; all P<0.05).During weekdays, compared with the non-myopia group, the myopia group had longer total near work duration, longer single continuous near eye use duration, shorter outdoor activity duration, closer eye use distance, larger proportion of near work time, and smaller proportion of outdoor activity time, showing statistically significant differences (all P<0.05).During weekends, compared with the non-myopia group, the myopia group had longer time spent looking at cell phones and computer screens, shorter outdoor activity time, greater proportion of time spent looking at cell phones and computer screens, and smaller proportion of outdoor activity time, with statistically significant differences (all P<0.05).During weekdays, after adjusting for confounding factors, longer single continuous near eye use duration ( OR=1.138, 95% CI: 1.086-1.192, P<0.001) was the risk factor for myopia, and longer working distance ( OR=0.906, 95% CI: 0.847-0.970, P=0.004) and longer outdoor activity time ( OR=0.127, 95% CI: 0.023-0.703, P=0.018) were protective factors for myopia.During weekends, after adjusting for confounding factors, longer time spent on looking at cell phone screens ( OR=2.437, 95% CI: 1.460-4.068, P<0.001) and longer time spent on looking at computer screens ( OR=2.260, 95% CI: 1.283-3.979, P=0.005) were risk factors for myopia, and longer outdoor activity time ( OR=0.624, 95% CI: 0.416-0.934, P=0.022) was the protective factor for myopia. Conclusions:The eyes with continuous near work, prolonged use of smartphone and computer screens, closer eye use distance, and less time spent outdoors have been confirmed to be significantly correlated with myopia based on objective monitoring data.When formulating intervention measures for myopia prevention and control in children, it is advocated to further pay attention to control the distance and duration of near work on weekdays and strengthen screen time management on weekends.

Objective To explore the clinical efficacy of single-port laparoscopy combined with gonado-tropin-releasing hormone agonist(GnRH agonist)in the treatment of deep infiltrating endometriosis and its influence on serum circATRNL1 levels,and analyze its predictive value for patient prognosis.Methods 220 patients with deep infiltrating endometriosis from June 2021 to October 2023 were enrolled as study subjects and divided into an experimental group(n=110)and a control group(n=110)according to different surgical methods.The experimental group received single-port laparoscopy surgery combined with GnRH agonist treatment,while the control group only received single-port laparoscopy surgery.The changes in circATRNL1 expression level before and after treatment between the two groups were compared,the short-term efficacy and long-term prognosis of the two groups were evaluated.Spearman correlation analysis was conducted to explore the relationship between circATRNL1 expression levels after treatment and long-term prognosis.All patients were regrouped based on whether they relapsed during follow-up into a relapse group(n=42)and a non-relapse group(n=178).The circATRNL1 levels before and after treatment were compared between the two groups,and the predictive value of circATRNL1 expression levels after treatment for long-term relapse after treatment in patients with endometriosis was analyzed using a receiver operating characteristic curve(ROC curve).Results After treatment,the serum circATRNL1 levels in the experimental group was significantly lower than that in the control group,the difference was statistically significant(P<0.05).The postoperative pain VAS score of the experimental group was significantly lower than that of the control group,and the quality of life was significantly better than that of the control group,the recurrence rate was significantly lower than that of the control group,and the differences were statistically significant(P<0.05).The pregnancy rate of the experimental group was higher than that of the control group,and the postoperative dysmenorrhea rate was lower than that of the control group,but the differences were not statistically significant(P>0.05).Spearman correlation analysis showed that circATRNL1 expression levels after treatment was positively correlated with relapse among long-term prognosis indicators(r=0.290,P<0.05),but had no significant correlation with pregnancy rate(r=0.060,P>0.05).Compared to patients in the non-relapse group,the relapse group had significantly higher serum circATRNL1 expression levels after treatment,the difference was statistically significant(P<0.05).ROC curve analysis showed that the area under the curve(AUC)for serum circATRNL1 expression levels in predicting long-term postoperative relapse in patients with endometriosis after treatment was 0.746,with a sensitivity of 64.29%and a specificity of 82.02%,indicating good predictive value.Conclusion The treatment regimen combining single-port laparoscopy with GnRH agonist can significantly reduce patients'pain levels,improve their quality of life,and decrease the recurrence rate.Furthermore,this combined therapy also notably decreases serum circATRNL1 levels.The serum circATRNL1 expression levels have good predictive value for the long-term recurrence of deep-infiltrating endometriosis patients post-surgery.