OBJECTIVE To investigate the protective effect of cryptotanshinone on premature ovarian insufficiency （POI） rats and its potential mechanism based on stromal cell-derived factor-1 （SDF-1）/CXC subfamily receptor 4 （CXCR4） axis. METHODS POI rat model was established by intraperitoneal injection of vinylcyclohexene （VCD）. The successfully modeled rats were randomly divided into model group， cryptotanshinone low-dose group （50 mg/kg）， cryptotanshinone high-dose group （100 mg/kg）， and cryptotanshinone high-dose+AMD3100 group （100 mg/kg cryptotanshinone+2.5 mg/kg CXCR4 inhibitor AMD3100）， with 10 rats in each group. Another 10 rats were injected with normal saline instead of VCD as the control group. Rats in each drug group were given intragastrical or （and） intraperitoneal injection of the corresponding drug once a day for 4 weeks. The levels of estradiol （E2）， luteinizing hormone （LH） and follicle-stimulating hormone （FSH） in serum and reactive oxygen species （ROS）， malondialdehyde （MDA）， superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in ovarian tissue were detected in each group. The morphology of ovarian tissue was observed. The cell apoptosis of ovarian tissue， as well as the mRNA expressions of SDF-1， CXCR4 and the protein expressions of caspase-3， B cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， SDF- 1， CXCR4 were detected. RESULTS Compared with the control group， the ovarian atrophied， the number of primitive follicles decreased， the number of atretic follicles increased， and the damage was obvious in the model group. Serum E2 level， SOD and GSH-Px levels in ovarian tissue， the mRNA expressions of SDF-1 and CXCR4， and the protein expressions of Bcl-2， SDF-1 and CXCR4 in ovarian tissue were all significantly decreased or down-regulated； the levels of FSH and LH in serum， ROS and MDA levels in ovarian tissue， the cell apoptosis rate， and the protein expressions of caspase-3 and Bax in ovarian tissue mail：k26awn@163.com were increased or upregulated significantly （P＜0.05）. Compared with model group， the ovarian tissue lesions of rats in cryptotanshinone low-dose and high-dose groups were significantly improved， and each quantitative index was significantly improved （P＜0.05）. AMD3100 could significantly reverse the improvement effect of cryptotanshinone on the above indexes （P＜0.05）. CONCLUSIONS Cryptotanshinone can reduce ovarian cell apoptosis and oxidative stress in POI rats by activating the SDF-1/CXCR4 axis， regulating serum hormone levels， thereby improving ovarian injury.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.

Objective:To analyze the failure patterns and survival after stereotactic body radiotherapy (SBRT) in patients with T 1-2N 0M 0 non-small cell lung carcinoma (NSCLC). Methods:Clinical data of early-stage NSCLC patients who received SBRT at Zhejiang Cancer Hospital from January 2012 to September 2018 were retrospectively analyzed. The primary observed endpoint was the pattern of disease progression, which was divided into intra-field recurrence, regional lymph node recurrence and distant metastasis. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier method. Univariate analysis was conducted by log-rank test, and multivariate analysis was performed by Cox's model.Results:A total of 147 patients with 156 lesions were included. The median follow-up time was 44.0 months (16.5-95.5 months). A total of 57 patients (38.8%) progressed: 14 patients (24.5%) had recurrence with the 1-, 3-, and 5-year local recurrence rates of 2.0%, 10.9%, and 14.3%, respectively; 36 patients (63.2%) had Distant metastasis with the 1-, 3- and 5-year distant metastasis rates of 12.2%, 22.4% and 28.6%, respectively; and 7 patients (12.3%) had recurrence complicated with distant metastasis. The 3-, 5- and 7-year OS rates were 80.5%, 64.2% and 49.9% for all patients, respectively. The median OS was 78.4 months. The 3-, 5- and 7-year PFS rates were 64.8%,49.5% and 41.5%, with a median PFS of 57.9 months (95% CI: 42.3-73.5 months). Univariate and multivariate analyses showed that biologically equivalent dose and age were the factors affecting the efficacy of SBRT (both P<0.05). Conclusion:Distant metastasis is the main failure pattern in patients with T 1-2N 0M 0 NSCLC after SBRT. High-risk population should be selected for further systematic treatment to improve the efficacy.

ObjectiveTo analyze the expression of Lactate dehydrogenase A（LDHA） in both renal cell carcinoma （RCC） tissue and RCC cell lines， and to investigate the impact of LDHA expression on the progression of RCC. MethodsFrom June 2018 to June 2022， totally 52 cases of RCC tissue samples and 49 cases of para-cancerous tissue samples were collected through surgical procedures from our hospital. LDHA expression was detected using immunohistochemistry （IHC）. The expression levels of LDHA in vitro were also detected in the normal human proximal tubule epithelial cell line HK-2 and renal cell carcinoma cell lines A498， Caki-2， ACHN， and 786-O by using qRT-PCR and Western blot. A recombinant plasmid carrying LDHA-shRNA was constructed and then transfected into 786-O cells to down-regulate the expression of LDHA. Tumor proliferative capacity was monitored using CCK-8 assay， clonal formation assay and EdU assessments. Additionally， cell glycolytic activity was assessed through glucose uptake assay， lactate secretion assay， and ECAR analysis. ResultsIHC analysis revealed significantly higher expression of LDHA in RCC tissue compared to adjacent tissues（P<0.05）. Furthermore， RCC tissues with higher TNM stage exhibited greater expression of LDHA than those with lower TNM stage （P<0.05）. The results of qRT-PCR and Western blot demonstrated that the expression of LDHA in each RCC cell line was significantly higher than that in HK-2（P<0.05）. After blocking the expression of LDHA in 786-O， there was a significant down-regulation of cell proliferation and glycolysis capacity （P<0.05）. ConclusionsThe expression of LDHA in RCC tissue and RCC cell lines is significantly overexpressed compared with normal one， particularly in those with higher TNM stage. Knockdown of the expression of LDHA significantly suppresses cell proliferation and aerobic glycolysis capacity in 786-O.

Objective: To analyze the allocation of human resources for chronic disease prevention and control of district/county-level centers for disease control and prevention(CDC) in China in 2020. Methods: Survey subjects were from National Chronic Noncommunicable Disease and Risk Factor Surveillance Sites and National Demonstration Areas for Chronic Noncommunicable Disease Prevention and Control (demonstration areas). A survey examining the allocation of human resources for chronic disease prevention and control at district/county-level CDC was conducted in December 2021 through the National Demonstration Areas Management Information System. The number and rate of allocation of human resources for chronic disease prevention and control in district/county-level CDC were analyzed and the Wilcoxon rank sum test was used to compare the difference between demonstration and non-demonstration areas and between urban and rural areas. The Kruskal-Wallis H test was used to compare the difference in east, central and west regions. The Gini coefficient and Theil index were used to evaluate the balance of human resource for chronic disease prevention and control. Results: A total of 678 districts/counties were investigated, and 664 districts/counties responded effectively, with an effective response rate of 97.9%. The establishment rate of district/county-level CDC was 98.34% (653/664), and the establishment rate of chronic disease prevention and control departments of district/county-level CDC was 96.02% (627/653). In 627 district/county-level CDC with departments for chronic disease prevention and control, the median number of full-time technical personnel for chronic disease prevention and control was 4, the median number of full-time technical personnel in demonstration areas (4 persons) was higher than in non-demonstration areas (3 persons), highest in the east region (5 persons) than in the middle region (4 persons) and the west region (4 persons), higher in urban areas (4 persons) than in rural areas (4 persons) (all P values<0.05). The allocation rate was 0.71 people/100 000, which was higher in demonstration areas (0.73 people/100 000) than in non-demonstration areas (0.67 people/100 000), highest in the west region (0.82 people/100 000) than in the middle region (0.71 people/100 000) and east region (0.67 people/100 000), higher in rural areas (0.77 people/100 000) than in urban areas (0.68 people/100 000) (all P values<0.05). The Gini coefficient for the allocation by population size was 0.352 9. The total Theil index for demonstration and non-demonstration areas, different regions, and urban-rural areas were 0.067 8, 0.076 3, and 0.000 2, with the intra-group contribution of 97.35%, 99.52%, and 98.80%, respectively. Conclusion: In 2020, the allocation of human resources for chronic disease prevention and control in district/county-level CDC is relatively balanced. The variation in the allocation of human resources for chronic disease prevention and control exist between demonstration and non-demonstration areas, urban and rural areas, and across regions.
Humans ; Noncommunicable Diseases/prevention & control* ; Workforce ; China ; Risk Factors ; Chronic Disease

To investigate the effects of leonurine(Leo) on abdominal aortic constriction(AAC)-induced cardiac hypertrophy in rats and its mechanism. A rat model of pressure overload-induced cardiac hypertrophy was established by AAC method. After 27-d intervention with high-dose(30 mg·kg~(-1)) and low-dose(15 mg·kg~(-1)) Leo or positive control drug losartan(5 mg·kg~(-1)), the cardiac function was evaluated by hemodynamic method, followed by the recording of left ventricular systolic pressure(LVSP), left ventricular end-diastolic pressure(LVESP), as well as the maximum rate of increase and decrease in left ventricular pressure(±dp/dt_(max)). The degree of left ventricular hypertrophy was assessed based on heart weight index(HWI) and left ventricular mass index(LVWI). Myocardial tissue changes and the myocardial cell diameter(MD) were measured after hematoxylin-eosin(HE) staining. The contents of angiotensin Ⅱ(AngⅡ) and angiotensin Ⅱ type 1 receptor(AT1 R) in myocardial tissue were detected by ELISA. The level of Ca~(2+) in myocardial tissue was determined by colorimetry. The protein expression levels of phospholipase C(PLC), inositol triphosphate(IP3), AngⅡ, and AT1 R were assayed by Western blot. Real-time quantitative PCR(qRT-PCR) was employed to determine the mRNA expression levels of β-myosin heavy chain(β-MHC), atrial natriuretic factor(ANF), AngⅡ, and AT1 R. Compared with the model group, Leo decreased the LVSP, LVEDP, HWI, LVWI and MD values, but increased ±dp/dt_(max) of the left ventricle. Meanwhile, it improved the pathological morphology of myocardial tissue, reduced cardiac hypertrophy, edema, and inflammatory cell infiltration, decreased the protein expression levels of PLC, IP3, AngⅡ, AT1 R, as well as the mRNA expression levels of β-MHC, ANF, AngⅡ, AT1 R, c-fos, and c-Myc in myocardial tissue. Leo inhibited AAC-induced cardiac hypertrophy possibly by influencing the RAS system.
Angiotensin II/metabolism* ; Animals ; Cardiomegaly/genetics* ; Gallic Acid/analogs & derivatives* ; Hypertrophy, Left Ventricular/pathology* ; Myocardium/pathology* ; Rats

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use* ; Citrates ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Respiration, Artificial ; Retrospective Studies

DNA is a biological polymer that encodes and stores genetic information in all living organism. Particularly, the precise nucleobase pairing inside DNA is exploited for the self-assembling of nanostructures with defined size, shape and functionality. These DNA nanostructures are known as framework nucleic acids (FNAs) for their skeleton-like features. Recently, FNAs have been explored in various fields ranging from physics, chemistry to biology. In this review, we mainly focus on the recent progress of FNAs in a pharmaceutical perspective. We summarize the advantages and applications of FNAs for drug discovery, drug delivery and drug analysis. We further discuss the drawbacks of FNAs and provide an outlook on the pharmaceutical research direction of FNAs in the future.

Objective:To analyze the medication rule of TCM compound prescription in the treatment of Primary Liver Cancer (PLC) in the National Patent Database by the method of data mining.Methods:By searching for the compound prescriptions of TCM which were included in the National Patent Retrieval Platform for the treatment of PLC, and analyzing the frequency, association and cluster of those included compound prescriptions through the inheritance and assistance platform of TCM.Results:A total of 350 patent prescriptions for the treatment of PLC were included, involving 425 Chinese medicines; the top 10 frequently appeared herbal medicines were Hedyotis diffusa, Radix Astragali, Scutellaria barbata, Atractylodes macrocephala, Glycyrrhiza uralensis, Ginseng, Radix Bupleuri, Rhizoma Curcumae, Salvia miltiorrhiza and Angelica sinensis; according to the function of those medicines, the top three frequently appeared herbal medicines were those with deficiency-tonifying heat-clearing and detoxifying, promoting blood circulation and removing blood stasis functions; the property of the medicine were mainly cold, warm and mild; the taste of the medicine were mainly bitter, sweet and acrid; the meridians of the medicines mainly belong to liver, spleen and lung. It was found that there were 12 association rules, and the medicine pair that were closely correlated was " Hedyotis diffusa- Scutellaria barbata", and the most frequently appeared medicines could be grouped into 8 groups. Conclusions:The TCM patent compound prescriptions mainly play the role of replenishing qi and invigorating the spleen, supplemented by the products of clearing heat and detoxification, activating blood circulation and removing blood stasis, which is consistent with the basic treatment principle of PLC "invigorate the upright and dispel the evil, attack the evil and tonify the body". This study explores the basic medication rules of TCM patent compound prescription in the treatment of PLC, in order to provide guidance for clinical practice.