Aim To investigate the role of metabolites of eicosapentaenoic acid (EPA) in promoting the transdifferentiation of pancreatic α cells to β cells. Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin (STZ) for five consecutive days to establish a type 1 diabetes (T1DM) mouse model. After two weeks, they were randomly divided into model groups and 97% EPA diet intervention group, 75% fish oil (50% EPA +25% DHA) diet intervention group, and random blood glucose was detected every week; after the model expired, the regeneration of pancreatic β cells in mouse pancreas was observed by immunofluorescence staining. The islets of mice (obtained by crossing GCG

Objective: To analyze the longitudinal association between mobile phone dependence and depressive symptoms in college students, so as to provide a theoretical basis for psychological health education among college students. Methods: From November 2021 to June 2023, 2 515 first year students from 2 universities in Yunnan Province were surveyed with a questionnaire by a cluster random sampling method, including baseline survey (November 2021, T1) and three follow up visits (June 2022, T2; November 2022, T3; June 2023, T4). The Self rating Questionnaire for Adolescent Problematic Mobile Phone Use and the Depression Anxiety Stress Scales-21 (DASS-21) were used to evaluate mobile phone dependence and depressive symptoms of college students. The χ 2 test was used to analyze the difference in depressive symptoms among different demographic groups, and a generalized estimation equation model was established to analyze the association between mobile phone dependence symptoms and depressive symptoms. Results: The detection rates of depressive symptoms among university students in Yunnan Province at time points T1, T2, T3, and T4 were 23.02%, 33.36%, 34.79% and 35.51%, respectively. There were statistically significant differences in the detection rates of depressive symptoms among college students with different sacademic burden (T1, T2, T3, T4), different number of close friends (T1, T2, T3), as well as their father s educational level (T1), mothers educational level (T2, T4), gender (T4), major (T3, T4), education (T2, T3, T4), family residency (T1, T2), and family economic conditions (T1, T2, T4) ( χ 2= 59.68 , 49.38, 16.70, 39.31; 55.35, 26.01, 16.69; 10.22; 14.87, 11.51; 14.90; 27.81, 50.28; 9.75, 7.42, 24.76; 6.06, 4.47 ; 15.88, 14.58, 15.85, P < 0.05 ). After controlling for demographic variables and confounding factors in the generalized estimation equation model, mobile phone dependence ( β =0.11), withdrawal symptoms of mobile phone dependence ( β =0.14), and the physical and mental effects of mobile phone dependence ( β =0.14) were all positively correlated with depressive symptoms ( P <0.01). Further gender analysis showed that depressive symptoms in both boys ( β =0.13, 0.13, 0.18) and girls ( β =0.10, 0.13, 0.13 ) were associated with mobile phone dependence, withdrawal symptoms of mobile phone dependence and the physical and mental effects of mobile phone dependence ( P <0.01). Conclusions Depressive symptoms of college students are positively correlated with mobile phone dependence, and family economic conditions, academic burden and number of close friends are factors that continued to affect depressive symptoms. College students should be guided to pay attention to the impact of excessive use of mobile phones on their physical and mental health, use mobile phones reasonably to reduce the incidence of depressive symptoms among college students.

Objective:To establish the pig model of cardiac arrest and resuscitation, and then investigate the protective role of sivelestat (SV) on the heart after resuscitation and its relation with β-catenin signaling pathway.Methods:Twenty-five healthy male white pigs were purchased. The animals were randomly divided into the Sham group ( n=6), cardiopulmonary resuscitation group (CPR, n=10), and CPR+SV group ( n=9). The experimental animal model was established by 9 min of cardiac arrest induced by the method of ventricular fibrillation and then 6 min of CPR in the CPR and CPR+SV groups. At 5 min after successful resuscitation, a dose of 10 mg/kg of SV was infused in a duration of 1h via the femoral vein with a micro-infusion pump in the CPR+SV group. Myocardial function evaluated by the values of stroke volume (SV) and global ejection fraction (GEF) was measured by PiCCO at baseline, and at 0.5, 1, 2, 4 h after resuscitation. The serum concentrations of cardiac injury biomarkers including cardiac troponin I (cTnI) and creatine kinase isoenzymes (CK-MB) were measured by ELISA using blood samples drawn from the femoral vein at baseline, and at 1, 2, 4, and 24 h after resuscitation. The animals were euthanized at 24 h after resuscitation, and then cardiac tissue samples were harvested to measure the protein expression levels of β-catenin, Cyclin D1, c-Myc, cleaved caspase-9, and cleaved caspase-3 by Western blot and the degree of cell apoptosis by TUNEL. Results:Prior to cardiac arrest, myocardial function and cardiac injury biomarkers were maintained at the same levels, and no differences were observed among the three groups (all P> 0.05). After resuscitation, myocardial dysfunction and cardiac injury were observed in the CPR and CPR+SV groups, in which the values of SV and GEF were significantly decreased and meanwhile the serum concentrations of cTnI and CKMB were significantly increased when compared with the Sham group (all P< 0.05). However, myocardial dysfunction and cardiac injury were significantly milder in the CPR+SV group, in which the value of SV at 4h post-resuscitation and the values of GEF starting 1h post-resuscitation were significantly increased, and the serum concentrations of cTnI and CKMB were significantly decreased at 4 and 24 h post-resuscitation when compared to the CPR group (all P< 0.05). Tissue measurements indicated that the change of β-catenin signaling pathway and the occurrence of cell apoptosis were observed in the heart at 24 h post-resuscitation in the CPR and CPR+SV groups, which were indicated by significant increases in the protein expression levels of β-catenin, Cyclin D1, c-Myc, cleaved caspase-9, and cleaved caspase-3, and marked elevation in the index of cell apoptosis when compared with the Sham groups (all P< 0.05). However, the expression levels of proteins mentioned above were significantly decreased in the heart at 24 h post-resuscitation and the index of cell apoptosis was significantly reduced in the CPR+SV group when compared to the CPR group (all P< 0.05). Conclusion:SV has the protective role in alleviating post-resuscitation myocardial dysfunction and cardiac injury, in which the protective mechanism is possibly related to the alleviation of cell apoptosis through the inhibition of β-catenin signaling pathway activation.

Objective To investigate the factors influencing the pregnancy outcomes during frozen-thawed embryo transfer(FET)cycles in patients with polycystic ovary syndrome(PCOS).Methods A retrospective analysis was conducted on patients'data from 882 FET cycles.According to the pregnancy outcome,the patients were divided into non-implantation group(Group A),abortion group(Group B1)and live birth group(Group B2).Clinical data and laboratory parameters were compared among the three groups,and ordered Logistic regression analysis was used to study the factors influencing pregnancy outcomes after FET.Patients were also divided into four groups(C1-C4)based on the number of high-quality embryos obtained(0-3,4-6,7-10,≥11),and their clinical data and laboratory parameters were compared.Results The clinical pregnancy rate,live birth rate,and miscar-riage rate in the 882 treatment cycles were 71.09%(627/882),61.68%(544/882),and 13.24%(83/627),respectively.Single-factor analysis showed significant differences in body mass index(BMI),infertility type,hu-man chorionic gonadotropin(hCG)day estradiol(E2)level,number of retrieved oocytes,and number of high-quality embryos among Groups A,B1,and B2(P<0.05).Further multiple Logistic regression analysis revealed that BMI(OR=1.046,95%CI:1.001-1.093,P=0.044)and a history of previous pregnancy(OR=1.417,95%CI:1.030-1.950,P=0.032)were independent risk factors for successful FET in PCOS patients,while an in-creased number of high-quality embryos was an independent protective factor for successful pregnancy.Based on the results of Group B2,compared to Group A,OR=0.920,95%CI:0.880-0.962,P=0.000;compared to Group B1,OR=0.923,95%CI:0.862-0.988,P=0.022.Compared with the other three groups(C1-C3),the total amount of gonadotropin(Gn)in the C4 group was the lowest and the number of oocytes obtained was the high-est(P<0.05).Multiple comparisons showed that Group C4 had lower BMI,follicle-stimulating hormone(FSH),very low-density lipoprotein(vLDL)levels,a higher luteinizing hormone and follicle-stimulating hormone(LH/FSH)ratio compared to Group C1(P<0.05).Group C4 had lower fasting insulin(FINS)and homeostasis model assessment of insulin resistance(HOMA-IR)levels compared to Group C3,and higher high-density lipoprotein-cholesterol(HDL-C)and apolipoprotein A1(Apo A1)levels compared to Groups C2 and C3(P<0.05).Con-clusion BMI,the history of previous pregnancy and the number of high-quality embryos were both independent factors for predicting pregnancy outcomes in PCOS patients undergoing FET cycles.Patients with a higher number of high-quality embryos have a higher clinical pregnancy rate during FET cycles.

Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

AIM To explore the clinical effects of Shuilu Erxian Pills combined with Modified Didang Decoction on patients with early and middle stage diabetic nephropathy.METHODS Eighty-three patients were randomly assigned into control group(42 cases)for 12-week administration of Irbesartan Tablets,and observation group(41 cases)for 12-week administration of Shuilu Erxian Pills,Modified Didang Decoction and Irbesartan Tablets.The changes in clinical effects,TCM syndrome scores,blood glucose indices(FBG,HbA1c),blood lipid indices(TC,TG),renal function indices(BUN,Scr,24 h UTP,eGFR),inflammatory factors(IL-1β,hs-CRP,IL-6,TNF-α,IL-18,TGF-β1),immune function indices(lymphocyte,neutrophil,CD8+,CD3+,CD4+,CD4+/CD8+)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the observation group displayed decreased TCM syndrome scores,blood glucose indices,blood lipid indices,BUN,Scr,24 h UTP,inflammatory factors,CD8+(P＜0.05),reduced lymphocyte,neutrophil(P＜0.05),and increased eGFR,CD3+,CD4+,CD4+/CD8+(P＜0.05),which were more obvious than those in the control group(except for HbA1c,TG,SCr,24 h UTP,lymphocyte,neutrophil)(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with early and middle stage diabetic nephropathy,Shuilu Erxian Pills combined with Modified Didang Decoction can safely and effectively improve clinical symptoms,whose mechanism may contribute to the reduction of inflammatory levels and improvement of immune functions.

Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

Objective To study the effect and pathological mechanisms of the neuro-immune response to viral encephalomyelitis caused by virulence reversion following the intrathalamic neurovirulence test for poliomyelitis vaccine in rhesus macaques.Methods Stock solutions(≥7000 lgCCID50/L)of inactivated polio vaccines(Vero cells)of type I,type Ⅱ,and type Ⅲ Sabin strains and 10-1 dilution of each type of polio vaccine were given to macaques,which were subjected to a intrathalamic neurovirulence test.Using immunohistochemical method,the pathological changes caused by polio,as determined by the distribution of CD 155 and CD4+receptor T lymphocytes,CD20+B lymphocytes,and CD68+microglia,were detected.Results Lesions were observed on the virulence-reverted polio cases.Inflammatory cell infiltration,neuronal degeneration and necrosis,satellite phenomena,perivascular cuffing,and glial cell proliferation were observed in the spinal cord.The inflammatory cells in the perivascular cuffing and proliferative glial nodules were mainly CD4+T lymphocytes,CD20+B lymphocytes,and CD68+microglia.There was no significant difference in the distribution of the poliovirus receptor CD 155 in the neurons and glial cells of monkeys with and without polio,and no expression was observed in their vascular endothelial cells.Conclusions Polio caused by virulence reversion of the intrathalamic neurovirulence test is viral encephalomyelitis.

OBJECTIVE: To investigate the occurrence of CSF3R mutation in patients with t(8;21) acute myeloid leukemia (AML) and its correlation with some clinical parameters. METHODS: The clinical and laboratory data of 167 newly diagnosed AML patients with t(8;21) translocation were analyzed retrospectively. High-throughput DNA sequencing technology combined with Sanger sequencing method was used to detect 112 gene mutations. The occurrence of CSF3R gene mutation and its influence on the remission rate after chemotherapy were analyzed. RESULTS: Among 167 patients with t(8;21) AML, 15 patients (9.0%) carried CSF3R mutations, including 6 cases of membrane proximal region mutations and 9 cases of truncation mutations in the cytoplasmic tail. The most common coexisting mutations of CSF3R were KIT (40.0%), TET2 (33.3%), DNMT3A (26.7%), FLT3 (20.0%), CBL (20.0%), IDH1 (13.3%), etc. Compared with the wild type, the CSF3R mutant group had a higher mutation rate of DNA methylation-related genes（P <0.001）. The median peripheral white blood cell (WBC) count of patients with CSF3R gene mutation was 5.80 (3.20-8.56)×10⁹/L at initial diagnosis, which was significantly lower than 8.80 (5.26-19.92)×10⁹/L of the CSF3R wild-type patients (P =0.017). There was no significant difference between the two groups in sex, median age, FAB classification, hemoglobin level, platelet count, etc. (P >0.05). The CR rate of the CSF3R gene mutation group (100%) was significantly higher than that of the wild-type group (86.8%), but the difference was not statistically significant (P >0.05). The CSF3R gene mutation group had a significantly higher CD19 positive rate and a higher -X rate than the wild group (86.7% vs 47.4%, P =0.004; 33.3% vs 13.2%, P =0.037). CONCLUSION There is a high incidence of CSF3R mutation in t (8;21) AML patients. The clinical characteristics and coexisting mutation genes of CSF3R mutation-positive patients are different from those of wild-type patients.
Humans ; Retrospective Studies ; Prognosis ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Signal Transduction ; Receptors, Colony-Stimulating Factor/genetics*

Objective:To investigate the effect of sodium butyrate (NaB) on renal and intestinal injury after cardiac arrest and cardiopulmonary resuscitation (CA-CPR) and its related mechanism.Methods:Twenty-four domestic healthy male swines were randomly divided into 3 groups: sham group ( n=6), CA-CPR group ( n=10) and NaB group ( n=8). The animals only underwent operational preparation in the sham group. The animal model of CA and CPR was established by 9 min of ventricular fibrillation induced by electrical stimulation in the ventricle and then 6 min of CPR in the CA-CPR and NaB groups. At 5 min after resuscitation, a dose of 75 mg/kg of NaB was intravenously infused for 1 h in the NaB group, and meanwhile the same volume of vehicle was intravenously infused in the sham and CA-CPR groups. At 1, 2, 4, and 24 h after resuscitation, blood samples were collected to detect the renal and intestinal injury biomarkers, such as creatinine (Cr), blood urea nitrogen (BUN), intestinal fatty acid binding protein (IFABP), and diamine oxidase (DAO). At 24 h after resuscitation, renal and intestinal tissue specimens were harvested to detect the protein markers of cell autophagy including microtubule-associated protein light chain 3 Ⅱ (LC3Ⅱ) and p62 expression, and also renal and intestinal apoptosis. Statistical analysis was performed by SPSS software, and continuous variables were compared with one-way analysis of variance among the groups. Results:After CA-CPR, the renal and intestinal injury biomarkers including Cr, BUN, IFABP, and DAO were significantly increased at all time points after resuscitation in the CA-CPR and NaB groups compared with the sham group (all P<0.05). The injury biomarkers mentioned-above were significantly lower at all time points after resuscitation in the NaB group than in the CA-CPR group [Cr (μmol/L): (90±5) vs. (127±9) at 1 h, (135±14) vs. (168±9) at 2 h, (174±10) vs. (211±12) at 4 h, (192±10) vs. (253±13) at 24 h; BUN (mmol/L): (10.5±1.0) vs. (12.3±1.0) at 1 h, (12.2±1.2) vs. (15.3±0.9) at 2 h, (13.6±1.3) vs. (18.3±1.2) at 4 h, (15.4±1.4) vs. (21.5±1.4) at 24 h; IFABP (pg/mL): (502±33) vs. (554±32) at 1 h, (574±52) vs. (644±41) at 2 h, (646±44) vs. (732±43) at 4 h, (711±42) vs. (828±42) at 24 h; DAO (U/mL): (8.6±1.0) vs. (10.5±0.9) at 1 h, (10.6±1.2) vs. (12.8±1.0) at 2 h, (12.1±1.0) vs. (15.0±1.0) at 4 h, (14.1±1.1) vs. (17.6±1.0) at 24 h, (all P<0.05)]. Renal and intestinal tissue detection indicated that cell autophagy and apoptosis were significantly increased after resuscitation in the CA-CPR and NaB groups compared with the sham group, which was indicated by significantly increased LC3Ⅱ and decreased p62 expression, and markedly elevated apoptosis index (all P<0.05). However, cell autophagy and apoptosis in the kidney and intestine were significantly milder after resuscitation in the NaB group than in the CA-CPR group [renal LC3 Ⅱ: (1.15±0.17) vs. (2.23±0.31), p62: (1.60±0.10) vs. (1.17±0.08), apoptosis index (%): (21.2±5.3) vs. (50.9±7.9); intestinal LC3 Ⅱ: (1.03±0.17) vs. (1.71±0.21), p62: (1.30±0.29) vs. (0.79±0.29), apoptosis index (%): (25.6±6.1) vs. (61.7±10.7), all P<0.05]. Conclusions:NaB could alleviate the severity of renal and intestinal damage after CA-CPR in swine, and its protective mechanism may be related to the inhibition of cell autophagy and apoptosis.