OBJECTIVE To investigate the mechanism of gossypol acetic acid （GAA） in the treatment of uterine fibroids. METHODS Human leiomyoma cells SK-UT-1 were selected as objects to investigate the effects of different concentrations （5， 10， 20， 40， 80， 160 μmol/L） of GAA on the activities of cell proliferation. 4D-DIA proteomic detection and bioinformatics analysis were carried out to screen differential proteins. Gene ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway analysis were performed. The expressions of top 3 proteins [N-myc downstream regulated gene 1 （NDRG1）， epidermal growth factor receptor feedback inhibitor 1 （ERRFI1）， CXC chemokine ligand 3 （CXCL3）] with differential fold changes in SK-UT-1 cells were determined. RESULTS 10-160 μmol/L GAA could significantly reduce the survival rate of SK- UT-1 cells （P＜0.05）. Proteomics results showed that a total of 921 differentially expressed proteins were obtained， including 254 up-regulated proteins and 667 down-regulated proteins. The differentially expressed proteins were mainly distributed in mitochondria， nucleus， extracellular matrix， etc. Bioinformatics results showed that differentially expressed proteins were mainly involved in signaling pathways such as PI3K/AKT （phosphoinositide 3-kinase/protein kinase B）， MAPK （mitogen-activated protein kinase）， TNF （tumor necrosis factor）， etc.， which mainly involved cell apoptosis， aging， and movement. GAA significantly decreased protein expressions of NDRG1 and CXCL3 （P＜0.05）， but increased protein expression of ERRFI1 （P＜0.05）. CONCLUSIONS The improvement effect of GAA on uterine fibroids may involve signaling pathways such as PI3K/AKT， MAPK， TNF， etc. It can improve the occurrence and development of uterine fibroids by downregulating the expressions of NDRG1 and CXCL3 proteins， upregulating the expression of ERRFI1 protein， and affecting the proliferation and apoptosis of uterine fibroid cells.

Objective:To summarize the clinical characteristics of patients with combined pneumocystis jiroveci pneumonia (PJP ) after allogeneic hematopoietic stem cell transplantation (allo-HSCT ). Methods:The clinical manifestations,laboratory tests,imaging findings,and treatment outcomes of 21 allo-HSCT patients with PJP diagnosed at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematology Hospital from July 2018 to July 2023 were retrospective analyzed.Results:Among the 21 patients,the male-to-female ratio was 2.5:1,and the median age was 36 years old with a range of 15-62 years.The median time to diagnosis of PJP after transplantation was 225 days.The clinical manifestations lack specificity,and the main clinical symptoms include respiratory symptoms (dyspnea,cough,sputum,etc.) and fever.Laboratory examination revealed peripheral blood lymphocyte counts decreased in 15 cases,CD4+T lymphocyte absolute values less than 200 cells/μl in 19 patients,C-reactive protein levels significantly increased in 20 patients,lactate dehydrogenase levels increased in 14 patients,and 1,3-β-D-glucan detection levels increased in 14 patients.Chest CT manifestations can be divided into three types:ground glass type,nodular type,and mixed type.Among them,the incidence of ground glass type was the highest (18/21),with 2 cases of nodular type and 1 case of mixed type.The sequence number of Pneumocystis jiroveci was detected through mNGS (15-57570),and 11 patients had mixed infections.In terms of treatment,TMP-SMX,Caspofungin,and methylprednisolone were administered,and 17 patients achieved improvement in their condition.Four patients died,all of whom died from respiratory failure.Conclusion:PJP is a critically ill condition after hematopoietic stem cell transplantation,and diagnosis is difficult.Early diagnosis can achieve better prognosis.The sensitivity of mNGS in diagnosing PJP is high,providing the possibility of early and accurate diagnosis for clinical practice,which is worthy of application and promotion.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To evaluate the therapeutic effects of Yufu ointment for acute radiation-induced skin injury. Methods:We enrolled a total of 104 patients with malignant tumors who developed acute skin injury of grade 2-3 during or after the first course of radiotherapy from June 2019 to February 2023. The observation group ( n=53) and control group ( n=51) received external application of Yufu ointment and Shirun Shaoshang ointment, respectively. We recorded the changes in the grade of skin injury and associated symptoms (such as pain, itching, and burning sensation) and healing speed and time for the two groups. Results:A total of 102 patients completed the study, with 53 cases in the observation group and 49 cases in the control group. The incidence rate of moisture skin lesions in the observation group was significantly lower than that in the control group (62.26% vs. 83.67%, P<0.05). The healing speed of moisture skin ulcerations was significantly faster in the observation group than in the control group (1.67 cm 2/d vs. 0.55 cm 2/d, P<0.05). The observation group had a significantly shorter time to skin injury healing than the control group (10.40 d vs. 14.41 d, P<0.05), significantly different for skin injury of grade 2 (10.21 d vs. 17.57 d, P<0.05) but not for skin injury of grades 2.5 and 3 ( P>0.05). Regarding clinical symptoms, both groups experienced significant reductions in pain and burning sensation scores after treatment ( P<0.05); the grade of itching was significantly decreased for the observation group ( P<0.05), but had no significant change for the control group after treatment ( P>0.05). Conclusions:Yufu ointment can significantly alleviate secondary damage for patients with acute radiation-induced skin injury, by accelerating the healing process and relieving symptoms such as pain, itching, and burning sensation with good tolerability, which deserves further promotion.

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

Objective:To investigate the morbidity of cerebrovascular disease among residents ≥30 years in Pengzhou, Sichuan Province, and analyze the effect of physical activity level on the risk of morbidity of cerebrovascular disease.Methods:From 2004 to 2008, people from Pengzhou, Sichuan Province were randomly selected. All the local people aged 30-79 were asked to receive a questionnaire survey, physical examination, and long-term follow-up to determine the morbidity of cerebrovascular disease. The physical activity level and the morbidity of cerebrovascular disease were described, and Cox proportional hazard regression models were used to evaluate the association of domain-specific physical activity with the risk of morbidity of cerebrovascular disease.Results:In 55 126 participants, there were 5 290 new cases of cerebrovascular disease, with a cumulative incidence of 9.60%. After the adjustment for multiple confounding factors, multivariate Cox proportional hazard regression analysis showed that increased levels of occupational, transportation, and total physical activity reduced the risk of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). The highest group of occupational physical activity level had the lowest risk of cerebrovascular disease, with a hazard ratio ( HR) value of 0.81 (95% CI: 0.75-0.88), the highest group of transportation physical activity level had the lowest risk of cerebrovascular disease, with an HR value of 0.84 (95% CI: 0.78-0.91), the highest group of total physical activity level had the lowest risk of cerebrovascular disease, with an HR value of 0.87 (95% CI: 0.80-0.94), compared with the lowest group of corresponding physical activity. No association was found between the household/leisure-time physical activity level and the risk of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). Conclusions:In project areas of Pengzhou, Sichuan Province, increased physical activity has been associated with reduced morbidity of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). Increased levels of physical activity in adults are encouraged for health benefits.

Humans ; Multiple Myeloma/drug therapy* ; Thalidomide/therapeutic use* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Neoplasm Recurrence, Local/drug therapy*

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.
Male ; Humans ; Middle Aged ; Atorvastatin/therapeutic use* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Hypercholesterolemia/drug therapy* ; Cholesterol, LDL/therapeutic use* ; Anticholesteremic Agents/therapeutic use* ; Treatment Outcome ; Triglycerides ; Apolipoproteins B/therapeutic use* ; Double-Blind Method ; Pyrroles/therapeutic use*

Objective: To analyze the trends of the age of menarche among Chinese Han girls aged 9 to 18 years from 2010 to 2019. Methods: Data were extracted from the Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019. A total of 253 037 Han girls aged 9 to 18 years with complete data on menarche were selected in this study. They were asked one-on-one about their menstrual status, age and residence information. The median age of menarche was estimated by probability regression. U tests were used to compare the difference in median age at menarche in different years. Results: The median age at menarche (95%CI) among Chinese Han girls was 12.47 (12.09-12.83) years in 2010, 12.17 (11.95-12.38) years in 2014 and 12.05 (10.82-13.08) years in 2019, respectively. Compared with that in 2010, the median age at menarche in 2019 decreased by 0.42 years (U=-77.27, P<0.001). The annual average changes were-0.076 years from 2010 to 2014 (U=-57.19, P<0.001) and-0.023 years from 2014 to 2019 (U=-21.41, P<0.001), respectively. The average annual changes in urban areas in the periods of 2010 to 2014 and 2014 to 2019 were-0.071 years and 0.006 years, respectively, while those in rural areas were-0.082 years and-0.053 years, respectively. The average annual changes in the regions of north, northeast, east, south central, southwest and northwest were-0.064, -0.099, -0.091, -0.080, -0.096 and-0.041 years in the period of 2010 to 2014 and 0.001, -0.040, -0.002, -0.005, -0.043 and-0.081 years in the period of 2014 to 2019. Conclusion: The age of menarche among Chinese Han girls aged 9 to 18 years shows an advanced trend from 2010 to 2019, and the trends in urban and rural areas and different regions have different characteristics.

Objective: To analyze the long-term trend of the age of spermarche among Chinese Han boys aged 11 to 18 from 2010 to 2019 and its association with nutritional status. Methods: The data from Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019 were used. The age, residence and spermarche of the participants were collected by questionnaire, and their height and weight were measured. A total of 184 633 Han boys aged 11‒18 years with complete data on spermarche, height, and weight were included in this study. The probability regression method was used to calculate the median age (95%CI) at spermarche in different areas, and the trend of age at spermarche in different groups was compared. The multivariate logistic regression model was used to analyze the association between nutritional status and spermarche of Chinese Han boys aged 11‒18 years. Results: The median age of spermarche (95%CI) was 13.85 (13.45-14.22) years old among Chinese Han boys aged 11‒18 years in 2019, with 0.18 years earlier than that in 2010. The median age at spermarche in urban and rural boys was 13.89 and 13.81 years, respectively. Compared with that in 2010, the age at spermarche in urban and rural boys was 0.08 and 0.27 years earlier, respectively. After adjusting for age, province and urban/rural areas, compared with normal weight, spermarche was negatively associated with wasting and positively associated with overweight and obesity, with OR (95%CI) about 0.73 (0.67-0.80), 1.09 (1.02-1.17) and 1.09 (1.01-1.18), respectively. Conclusion: The age of spermarche generally shows an advanced trend among Chinese Han boys and is associated with nutritional status.