OBJECTIVE To analyze the characteristics of pediatric medicines with priority review and approval for marketing in China， providing a reference for promoting enterprise R&D and production， as well as improving the supply guarantee mechanism for pediatric medicines. METHODS Based on publicly available data sources such as List of Approved Information for Pediatric Medications Subject to Priority Review and Approval， Pharnexcloud biomedical database， and National Medical Insurance Drug Directory， this study conducted a comprehensive analysis of the main characteristics of pediatric medicines with priority review and approval for marketing. RESULTS As of June 30， 2024， a total of 68 pediatric medicines had been approved through the priority review and approval process， covering 12 therapeutic areas， with oral dosage forms accounting for 64.71%. The median time from application to inclusion in priority review was 35.50 days， with an average of 41.69 days. The median time from inclusion in priority review to market approval was 1.24 years， with an average of 1.42 years. This included 12 domestic new medicines， 21 domestic generic medicines， 35 imported medicines， as well as 29 pediatric-specific medicines and 21 orphan medicines. Additionally， 31 of these medicines had been included in the medical insurance catalog， representing a proportion of 45.59%. CONCLUSIONS Currently， a trend of differentiated competition is emerging between domestic and imported pediatric medicines. The therapeutic areas for pediatric medicines are continuously expanding， and the dosage forms are becoming more tailored to children’s needs. However， there are still issues such as slow progress in new medicine development， insufficient stability in the medicine review and approval process， and a need to increase the proportion of medicines included in medical insurance.

Objective To investigate the geographical distribution and seasonal fluctuations of visceral leishmaniasis vectors sandflies in Henan Province in 2023, so as to provide insights into the prevention and control of visceral leishmaniasis vectors. Methods A total of 23 counties (districts) were sampled from 18 cities of Henan Province from May to September, 2023 as sandfly surveillance sites, and sandflies were captured using human capture and light trapping methods. Following morphological identification, the changes in the sandfly density were calculated at different months and in different breeding habitats. Results A total of 406 light traps were set at sandfly surveillance sites in Henan Province from May to September, 2023, and a total of 3 137 female sandlies were captured, with an average density of 7.73 sandlies/(light·night). A total of 1 494 Phlebotomus chinensis sandflies were captured, including 1 222 female sandflies, with an average density of 3.01 sandflies/(light·night), and the highest density of P. chinensis was found in Gongyi City [17.00 sandflies/(light·night)]. A total of 5 544 sandflies were captured using the human capture method, including 230 P. chinensis, and the density of P. chinensis appeared a unimodal distribution, with a peak in early July [5.81 sandflies/(light·night)]. Among different breeding habitats, the highest P. chinensis density was detected in pigpens [4.50 sandflies/(light·night)]. Conclusions P. chinensis was predominantly distributed in hilly areas of northern and central-western Henan Province in 2023, and the sandfly density appeared a unimodal distribution. Intensified monitoring of visceral leishmaniasis vectors is recommended.

Objective To characterize the species of common sandflies in Henan Province using DNA barcoding with cytochrome c oxidase subunit I (COI) gene as the molecular marker, and to analyze the genetic polymorphisms of sandflies, so as to provide insights into visceral leishmaniasis prevention and control in Henan Province. Methods Sandfly specimens were sampled from 13 sandflies surveillance sites from 2021 to 2023 in Anyang City, Zhengzhou, Luoyang and Xuchang cities (Zhengzhou-Luoyang-Xuchang areas) where visceral leishmaniasis cases were reported and in Jiaozuo and Xinxiang cities (Jiaozuo-Xinxiang areas) without visceral leishmaniasis cases reported. Genomic DNA was extracted from a single sandfly, and COI gene was amplified. The amplification product was subjected to bidirectional sequencing. Following sequence assembly, the species of sandflies was characterized through sequence alignment using the BLAST tool. The intra-specific and inter-specific genetic distances of sandflies were estimated among different areas using the software Mega 11, and phylogenetic trees were created. The polymorphisms of nucleotide sequences in the sandflies COI gene were estimated using the software DnaSP. The fixation index (F_ST) of different geographical isolates of sandflies was calculated using the Arlequin software, and the gene flow value (Nm) was used to measure the gene flow in the sandflies populations. In addition, the population genetic structure of different geographical populations of Phlebotomus chinensis was analyzed using the STRUCTURE software. Results A total of 978 sandflies were collected from 13 sandflies surveillance sites in Zhengzhou-Luoyang-Xuchang areas, Jiaozuo-Xinxiang areas and Anyang City of Henan Province from 2021 to 2023, and 475 sandflies were randomly sampled for subsequent detections. A total of 304 Ph. chinensis, 162 Se. squamirostris and 9 Se. bailyi were identified based on molecular biological detection of the COI gene, and Se. bailyi was reported for the first time in Henan Province. The intraspecific genetic distances of sandflies were 0.000 to 0.040, and the inter-specific genetic distances ranged from 0.133 to 0.161. Phylogenetic analysis revealed that each of the three sandfly species was clustered into a clade. The genetic polymorphisms of Ph. chinensis populations varied among different areas, with the highest haplotype diversity (0.966 ± 0.007) and the greatest nucleotide diversity (0.011) in Zhengzhou-Luoyang-Xuchang areas, and the lowest haplotype diversity (0.720 ± 0.091) and nucleotide diversity (0.004) in Anyang City. The dominant haplotype of Ph. chinensis populations was Pch_Hap_2 in Anyang City and Jiaozuo-Xinxiang areas, with moderate genetic differentiation (0.05 < F_ST < 0.15) and frequent gene exchange (Nm value > 1) between Ph. chinensis populations sampled from Anyang City, and Jiaozuo-Xinxiang areas. Population genetic structure analysis showed that the dominant component of Ph. chinensis populations was K5 in Anyang City and Jiaozuo-Xinxiang areas. No obvious dominant haplotype was observed in Ph. chinensis populations sampled from Zhengzhou-Luoyang-Xuchang areas, which had very high genetic differentiation (F_ST > 0.25) and little gene exchange (Nm value < 1) with Ph. chinensis populations from Anyang City, and Jiaozuo-Xinxiang areas, with K3 as the dominant component. In addition, there was no significant difference in the genetic polymorphism level among Se. squamirostris populations from the three areas. Conclusions There are Ph. chinensis, Se. squamirostris and Se. bailyi in Henan Province, and S. bailyi is recorded for the first time in Henan Province by molecular biological assays. There are different levels of genetic differentiation and gene exchange among P. chinensis populations in different areas of Henan Province.

Objective To analyze the characteristics of visceral leishmaniasis cases in Henan Province, so as to provide insights into formulation of the visceral leishmaniasis control srtrategy. Methods All epidemiological data of reported visceral leishmaniasis cases in Henan Province from 2021 to 2023 were retrieved from the National Notifiable Disease Report Information Management System of Chinese Center for Disease Control and Prevention, and the epidemiological features and diagnosis of visceral leishmaniasis cases were descriptively analyzed. Results A total of 93 visceral leishmaniasis cases were reported in Henan Province from 2021 to 2023, with a male to female ratio of 2.58∶1, and including 2 imported cases from other provinces and 91 local cases. The number of visceral leishmaniasis cases peaked during the period between March and May, and between July and October. The reported visceral leishmaniasis cases had ages of 7 months to 74 years, with the largest number of cases found at ages of 0 to 9 years (26 cases, 27.96%), followed by at ages of 60 to 70 years (24 cases, 25.81%). Farmer (47 cases, 50.54%) and diaspora children (19 cases, 20.43%) were predominant occupations, and 91 local visceral leishmaniasis cases were found in 6 cities of Zhengzhou, Luoyang, Anyang, Hebi, Sanmenxia and Xuchang. The median duration from onset of visceral leishmaniasis to diagnosis was 20 days, and there were 25.81% (24/93) cases with 10 days and less duration from onset to diagnosis, 38.71% (36/93) cases receiving diagnosis at 11 to 30 days following onset, and 35.48% (33/93) cases receiving diagnosis for more than 30 days following onset. All cases were predominantly diagnosed in province- (60.00%) and city-level (28.89%) medical institutions. Conclusions The number of visceral leishmaniasis is on the rise in Henan Province, with a gradually expanding coverage. Intensified monitoring of visceral leishmaniasis cases, dogs, and vectors, dog management, sandflies control and improved individual protection are recommended to prevent the spread of visceral leishmaniasis.

Aim To investigate the protective effect of remimazolam(Re)combined with thoracic sympathetic nerve block(TSNB)on myocardial ischemia/reperfusion(MI/R)rats.Methods Rats were randomly separated into control group,MI/R group,Re group,TSNB group,and Re+TSNB group,with 12 rats in each group.Except for the control group,the remaining rats were subjected to left anterior descending coronary artery(LAD)ligation to construct an MI/R model.In the Re group,20 mg/kg Re was intraperitoneally injected 30 min before ischemia.In TSNB group,0.2％ropivacaine 50 μL was injected into the thoracic epidural catheter 30 min before ischemia.In the Re+TSNB group,20 mg/kg Re was intraperitoneally injected and 0.2％ropivacaine 50 μL was injected into the thoracic epidural catheter 30 min before ischemia.The control group and MI/R group were injected with normal saline only.Rats in each group were evaluated for cardiac function and infarct size.HE staining and TUNEL staining were applied to observe pathological changes in myocardial tissue and myocardial cell apoptosis.Serum myocardial injury markers creatine kinase(CK)and aspartate transaminase(AST),cardiac troponin(cTnⅠ),myocardial inflammatory factors interleukin-8(IL-8),tumor nec-rosis factor-α(TNF-α),and oxidative stress factors malondialdehyde(MDA),superoxide dismutase(SOD)were detec-ted.Western blot was applied to detect the expression of IL-8,TNF-α,B lymphoblastoma-2-associated X protein(Bax),and B-lymphoblastoma-2(Bcl-2)in myocardial tissue.Results Compared with the control group,the myocardial cells of rats showed edema and myocardial fiber disorder in the MI/R group,the left ventricular developmental pressure(LVDP),maximal left ventricular pressure rising rate(+dp/dtmax),maximal left ventricular pressure decreasing rate(-dp/dtmax),SOD activity,and level of Bcl-2 were significantly reduced,the myocardial infarction area,cell apoptosis rate,levels of cTnⅠ,CK,AST,IL-8,TNF-α,MDA,and Bax were increased(P＜0.05).Compared with the MI/R group,the morphology of myocardial fibers and myocardial cells was significantly improved in the Re group,TSNB group and Re+TSNB group,the LVDP,±dp/dtmax,SOD activity,and level of Bcl-2 were significantly increased,the myocardial infarction area,cell apoptosis rate,levels of cTnI,CK,AST,IL-8,TNF-α,MDA,and Bax were significantly decreased(P＜0.05).Compared with the Re group and TSNB group,the LVDP,±dp/dtmax,SOD activity,and level of Bcl-2 were significantly increased in the Re+TSNB group,the myocardial infarction area,cell apoptosis rate,levels of cTnⅠ,CK,AST,IL-8,TNF-α,MDA,and Bax were significantly decreased(all P＜0.05).Conclusion The combination of Re and TSNB may protect against MI/R injury by reducing myocardial infarction and myocardial cell apoptosis,and inhibiting inflammatory response and oxidative stress.

Objective:To investigate the specimen quality of intersphincteric resection with transabdominal transanal mixed approach for rectal cancer in the Chinese Transanal Total Mesorectal Excision Registry Collaborative (CTRC) database.Methods:The retrospective case-control study was conducted. Based on the concept of real-world research, the clinicopathological data of 281 pati-ents with rectal cancer in the CTRC database who underwent intersphincteric resection with trans-abdominal transanal mixed approach in 19 medical centers, including the Beijing Friendship Hospital of Capital Medical University et al, from November 15,2017 to December 31,2023 were collected. There were 196 males and 85 females, aged 61(range, 27-87)years. Observation indicators: (1) preoperative examinations; (2) neoadjuvant therapy; (3) postoperative examinations; (4) analysis of influencing factors for positive circumferential margin in surgical specimen of intersphincteric resec-tion for rectal cancer. Measurement data with normal distribution were represented as Mean±SD. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. The chi-square test was used for univariate analysis. Logistic regression model was used for multivariate analysis. Results:(1) Preoperative examinations. Of the 281 patients, 234 cases underwent preoperative pelvic magnetic resonance imaging (MRI) examina-tion. There were 2 cases in clinical stage T0, 3 cases in clinical stage T1, 58 cases in clinical stage T2, 137 cases in clinical stage T3, 24 cases in clinical stage T4, 3 cases in clinical stage Tx, 7 cases missing clinical T staging data. There were 87 cases in clinical stage N0, 68 cases in clinical stage N1, 60 cases in clinical stage N2, 9 cases in clinical stage Nx, 10 cases missing clinical N staging data. There were 30 cases with mesorectal fascia invasion, 53 cases with extramural venous invasion. The distance from lower margin of tumor to anal margin was 41.9(range, 1.0-80.0)mm. (2) Neoadjuvant therapy. Of the 281 patients, 125 cases underwent neoadjuvant therapy, including 39 cases receiving chemo-therapy alone, 6 cases receiving short-course simultaneous chemoradiotherapy, 5 cases receiving short-course simultaneous chemoradiotherapy and delayed surgery, 48 cases receiving long-course simultaneous chemoradiotherapy, 2 cases receiving other treatments, and 25 cases missing neoadju-vant therapy data. (3) Postoperative examinations. Of the 281 patients, 249 cases achieved R 0 resection, 9 cases achieved R 1 resection, and there were 23 cases missing surgical margin data. The maximum tumor diameter, the number of lymph nodes harvested and positive rate of vessel carcinoma embolus were 30.0(range, 0.5-200.0)mm, 13(range, 0-70) and 27.55%(73/265) in 281 patients. There were 252 patients with circumferential margin records, showing positive in 15 cases, with a positive rate as 5.95%(15/252). The minimum distance from deep part of tumor to circumferential margin was 7.0(range, 0-150.0)mm in 252 patients. There were 85 cases with distal margin records, showing positive in 1 case, and the distance from lower margin of tumor to distal margin was 10.0(range, 0-202.0)mm. There were 273 patients with specimen integrity records, which showed intact specimen in 208 cases, fair specimen in 58 cases, poor specimen in 4 cases, unevaluated specimen in 3 cases. There were 7 cases with rectal perforation. Of the 281 patients, cases in pathological stage T0, Tis, T1, T2, T3, T4 were 14, 5, 22, 107, 113, 12, respectively, and there were 8 cases missing pathological T staging data. Of the 281 patients, cases in pathological stage N0, N1a, N1b, N1c, N2a, N2b were 176, 27, 27, 11,20, 12, respectively, and there were 8 cases missing pathological N staging data. Of the 281 patients, there were 4 cases with distant metastasis, 262 cases without distant metastasis, 5 cases not evaluated, and 10 cases missing tumor metastasis data. Of the 125 patients undergoing neoadjuvant therapy, there were 85 cases with tumor regression grade records, including 16 cases as grade 1, 27 cases as grade 2, 19 cases as grade 3, 15 cases as grade 4, 8 cases as grade 5. (4) Analysis of influencing factors for positive circumferential margin in surgical specimen of intersphincteric resection for rectal cancer. Results of univariate analysis showed that preoperative T staging on preoperative pelvic MRI, mesorectal fascia invasion, extramural venous invasion, pathological T staging, and pathological N staging were related factors for positive circumferential margin in surgical specimen of intersphincteric resection for rectal cancer ( P<0.05). Conclusions:Intersph-incteric resection with transabdominal transanal mixed approach has good specimen quality and low positive rate of surgical margin. T staging on preoperative pelvic MRI may be related to positive circumferential margin after intersphincteric resection for rectal cancer.

Objective:To investigate the association of serum cholinesterase(ChE) with insulin resistance(IR) in patients with type 2 diabetes mellitus(T2DM).Methods:General information and laboratory results of 376 hospitalized patients with type 2 diabetes were collected from the Endocrinology Department of Xuzhou Medical University Affiliated Hospital from June 2020 to November 2022. Based on quartile levels of serum cholinesterase(ChE), the patients were divided into four groups: Q1 group(≤7 912 IU/L), Q2 group(7 913-9 083 IU/L), Q3 group(9 084-10 304 IU/L), and Q4 group(≥10 305 IU/L). The Homeostasis model was used to evaluate insulin resistance(HOMA-IR) for each group, and the correlation between ChE and HOMA-IR was analyzed. Results:As ChE levels increased, HOMA-IR levels significantly increased( P<0.05). Spearman correlation analysis showed that ChE was positively correlated with body mass index, diastolic blood pressure, high-sensitivity C-reactive protein, HbA 1C, total cholesterol, triglycerides, low density lipoprotein-cholesterol(LDL-C), aspartate aminotransferase, alanine aminotransferase(ALT), glutamyl transpeptidase, prealbumin, albumin, uric acid, and HOMA-IR( P<0.05). ChE was negatively correlated with age, duration of diabetes, and blood urea nitrogen( P<0.05). Multivariat stepwise linear regression analysis showed that disease duration, body mass index, HbA 1C, ALT, and ChE were independent influencing factors of HOMA-IR( P<0.01). Logistic regression analysis showed that compared to the Q1 group, the risks of developing IR in the Q4, Q3, and Q2 groups were 3.969(1.791-8.797), 2.100(1.059-4.164), and 2.026(1.071-3.833), respectively. Conclusion:Serum ChE is closely associated with IR in patients with T2DM.

Marsdenia tenacissima injection, a standard Marsdenia tenacissima extract (MTE), has been approved as an adjuvant therapeutic agent for various cancers. Our previous study showed that MTE inhibited the proliferation and metastasis of prostate cancer (PCa) cells. However, the underlying mechanisms and active ingredients of MTE against PCa were not completely understood. This study revealed that MTE induced significant decreases in cell viability and clonal growth in PCa cells. In addition, MTE induced the apoptosis of DU145 cells by reducing the mitochondrial membrane potential and increasing the expression of Cleaved Caspase 3/7, Cyt c, and Bax. In vivo, DU145 xenografted NOD-SCID mice treated with MTE showed significantly decreased tumor size. TUNEL staining and Western blot confirmed the pro-apoptotic effects of MTE. Network pharmacology analysis collected 196 ingredients of MTE linked to 655 potential targets, and 709 PCa-associated targets were retrieved, from which 149 overlapped targets were screened out. Pathway enrichment analysis showed that the HIF-1, PI3K-AKT, and ErbB signaling pathways were closely related to tumor apoptosis. Western blot results confirmed that MTE increased the expression of p-AKT^Ser473 and p-GSK3β^Ser9, and decreased the expression of p-STAT3^Tyr705in vitro and in vivo. A total of 13 compounds in MTE were identified by HPLC-CAD-QTOF-MS/MS and UPLC-QTOF-MS/MS. Molecular docking analysis indicated that six compounds may interact with AKT, GSK3β, and STAT3. In conclusion, MTE induces the endogenous mitochondrial apoptosis of PCa by regulating the AKT/GSK3β/STAT3 signaling axis, resulting in inhibition of PCa growth in vitro and in vivo.
Mice ; Animals ; Male ; Humans ; Mice, Inbred NOD ; Mice, SCID ; Marsdenia ; Proto-Oncogene Proteins c-akt ; Glycogen Synthase Kinase 3 beta ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Tandem Mass Spectrometry ; Prostatic Neoplasms ; Apoptosis ; STAT3 Transcription Factor

Objective To analyze the epidemiological characteristics of echinococcosis cases reported in the National Notifiable Disease Report System in Henan Province from 2010 to 2011, so as to provide insights into for echinococcosis control and surveillance. Methods The data pertaining to reported echinococcosis cases in Henan Province from 2010 to 2021 were retrieved from the National Notifiable Disease Report System, and a descriptive epidemiological analysis was performed using the software SPSS 22.0. Results A total of 150 echinococcosis cases were reported in Henan Province from 2010 to 2021, including 88 confirmed cases (58.67%) and 62 clinically diagnosed cases (41.33%), 77 cases reported by Henan Province (51.33%) and 73 cases reported by other provinces (48.67%). Echinococcosis cases were reported in each month, with 8 to 21 cases reported in each month, and the number of reported echinococcosis cases appeared no remarkable temporal changes. The echinococcosis cases were reported across 18 cities of Henan Province, with the highest number of cases reported in Zhoukou (17.33%) and Nanyang cities (17.33%) and the lowest number reported in Sanmenxia City (0.67%). The reported echinococcosis cases had a male to female ratio of 1.17:1, and the cases were found at each age group, with the the highest number of cases seen at ages of 20 to 59 years (73.33%). Farmer was the predominant occupation (63.33%), followed by housekeepers and the unemployed (12.67%). Of all reported echinococcosis cases, there were 25 local cases (16.67%) and 125 imported cases (83.33%), 144 cases reported by medical institutions (96.00%) and 6 cases reported by centers for disease control and prevention (4.00%). Conclusions Although imported echinococcosis cases were the predominant source of echinococcosis cases reported in the National Notifiable Disease Report System in Henan Province from 2010 to 2021, there were still sporadic local cases, and the emergence of local sources of infection cannot be excluded. Further expanded field surveys and surveillance of echinococcosis are required.

Objective:To explore the correlation between preoperative nutritional status and postoperative complications in elderly patients with right-sided colon cancer.Methods:A prospective registry database of 1, 196 patients undergoing curative surgery for right-sided colon cancer was collected from 52 top-tier hospitals nationwide between September 2021 and June 2022. The cohort included 627 males and 569 females, with an age range of 64(53, 71) years. Among these, 136 patients developed complications, while 1, 060 did not. Patients were divided into two groups based on age: the elderly group(≥65 years, n=571) and the middle-aged group(<65 years, n=625). Preoperative nutritional assessment indicators, clinical pathological data, and the incidence of complications within 30 days post-surgery were collected. For normally distributed quantitative data, mean ± standard deviation( ± s) was used, and the t-test was applied for intergroup comparisons. Non-normally distributed quantitative data were represented as M( Q1, Q3) and analyzed using the Wilcoxon rank-sum test; categorical data were compared using the chi-square test or Fisher′s exact test. In the analysis of risk factors for postoperative complications in elderly patients, univariate analysis was first conducted on all potential risk factors, followed by the inclusion of statistically significant variables from univariate regression into a multivariate logistic regression model. Results:The overall incidence of postoperative complications was 11.37%(136/1 196), with common complications includin wound infection(2.26%), intestinal obstruction (2.26%), anastomotic leakage(1.42%), deep vein thrombosis(1.42%), and chylous leakage(1.42%). In the elderly group, the proportion of patients with preoperative nutritional risk who developed complications was significantly higher than those without complications(66.20% vs. 53.40%, P=0.043). In the multivariate analysis, body mass index( OR=1.058, 95% CI: 1.005-1.117, P=0.031) and nutritional risk( OR=1.803, 95% CI: 1.066-3.126, P=0.031) were identified as independent risk factors for postoperative complications in elderly patients. Conclusions:There is a correlation between preoperative nutritional status and the occurrence of postoperative complications in elderly colon cancer patients, particularly with respect to body mass index and nutritional risk. These findings underscore the importance of preoperative nutritional assessment and intervention in elderly patients to reduce the risk of postoperative complications.