Objective:To explore the impact on safety and prognosis in patients with right-sided colon cancer participating in surgical clinical research.Methods:This retrospective cohort study utilized data from a randomized controlled trial (RELARC study) conducted by the colorectal surgery group at Peking Union Medical College Hospital in which laparoscopic complete mesocolic excision (CME) was compared with D2 radical resection for the management of right-sided colon cancer. The eligibility criteria were age 18–75 years, biopsy-proven colon adenocarcinoma, tumor located between the cecum and right 1/3 of the transverse colon, enhanced chest, abdomen, and pelvic CT scans suggesting tumor stage T2–T4N0M0 or TanyN+ M0, and having undergone radical surgical treatment from January 2016 to December 2019. Exclusion factors included multiple primary colorectal cancers, preoperative stage T1N0 or enlarged central lymph nodes, tumor involving surrounding organs requiring their resection, definite distant metastasis or otherwise unable to undergo R0 resection, history of any other malignant tumors within previous 5 years, intestinal obstruction, perforation, or gastrointestinal bleeding requiring emergency surgery, and assessed as unsuitable for laparoscopic surgery. Patients who had participated in the RELARC study were included in the RELARC group, whereas those who met the inclusion criteria but refused to participate in the RELAEC study were included in the control group. The main indicators studied were the patient's baseline data, surgery and perioperative conditions, pathological characteristics, adjuvant treatment, and postoperative follow-up (including average frequency of follow-up within the first 3 years) and survival (including 3-year disease-free survival rate (DFS) and 3-year overall survival rate (OS). Differences in these indicators between the RELARC and control groups were compared.Results:The study cohort comprised 290 patients, 173 in the RELARC group (RELARC-CME group, 82; RELARC-D2 group, 91) and 117 in the control group (CME control group, 72; D2 control group, 45). There was a significantly higher proportion of overweight patients (BMI ≥24 kg/m 2) in the RELARC-CME than in the CME control group (67.1% [55/82] vs. 33.3% [24/72], χ 2=17.469, P<0.001). There were no other statistically significant differences in baseline characteristics (all P>0.05). No significant disparities were found between the CME and D2 groups in terms of operation duration, intraoperative blood loss, rate of conversion to open surgery, combined organ resection, intraoperative blood transfusion, or intraoperative complications (all P>0.05). There was a trend toward Clavien–Dindo grade II or higher postoperative complications in the RELARC-CME group (24.4% [20/82]) than in the CME control group (18.1% [13/72]); however, this difference was not statistically significant (χ 2=0.914, P=0.339). Similarly, the difference in this rate did not differ significantly between the RELARC-D2 group (25.3% [23/91]) and D2 control group (24.4% [11/45], χ 2=0.011, P=0.916). The median duration of postoperative follow-up was significantly shorter in the RELARC groups than in the corresponding control groups. Specifically, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-CME and 7.2 (6.0, 9.0) months in the CME control group ( Z=-10.608, P<0.001). Similarly, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-D2 group as opposed to 8.3 (6.6, 9.0) months in the D2 control group ( Z=-10.595, P<0.001). The 3-year DFS rate (91.5%) and OS rate (96.3%) tended to be higher in the RELARC-CME group than in the CME control group (84.7% and 90.3%, respectively). The 3-year DFS rate (87.9%) and OS rate (96.7%) tended to be higher in the RELARC-D2 group than in the D2 control group (81.8% and 88.6%, respectively); however, these differences were not statistically significant (all P>0.05). Subgroup analysis according to pathological stage revealed that patients in the RELARC-D2 group with pN0 stage achieved a significantly superior 3-year OS rate than did those in the D2 control group (100% vs. 88.9%, P=0.008). We identified no statistically significant differences in survival rates between the remaining subgroups (all P>0.05). Conclusions:A high-quality surgical clinical trial with close follow-up can achieve perioperative safety and a trend toward improved survival outcomes.

Objective:To explore the impact on safety and prognosis in patients with right-sided colon cancer participating in surgical clinical research.Methods:This retrospective cohort study utilized data from a randomized controlled trial (RELARC study) conducted by the colorectal surgery group at Peking Union Medical College Hospital in which laparoscopic complete mesocolic excision (CME) was compared with D2 radical resection for the management of right-sided colon cancer. The eligibility criteria were age 18–75 years, biopsy-proven colon adenocarcinoma, tumor located between the cecum and right 1/3 of the transverse colon, enhanced chest, abdomen, and pelvic CT scans suggesting tumor stage T2–T4N0M0 or TanyN+ M0, and having undergone radical surgical treatment from January 2016 to December 2019. Exclusion factors included multiple primary colorectal cancers, preoperative stage T1N0 or enlarged central lymph nodes, tumor involving surrounding organs requiring their resection, definite distant metastasis or otherwise unable to undergo R0 resection, history of any other malignant tumors within previous 5 years, intestinal obstruction, perforation, or gastrointestinal bleeding requiring emergency surgery, and assessed as unsuitable for laparoscopic surgery. Patients who had participated in the RELARC study were included in the RELARC group, whereas those who met the inclusion criteria but refused to participate in the RELAEC study were included in the control group. The main indicators studied were the patient's baseline data, surgery and perioperative conditions, pathological characteristics, adjuvant treatment, and postoperative follow-up (including average frequency of follow-up within the first 3 years) and survival (including 3-year disease-free survival rate (DFS) and 3-year overall survival rate (OS). Differences in these indicators between the RELARC and control groups were compared.Results:The study cohort comprised 290 patients, 173 in the RELARC group (RELARC-CME group, 82; RELARC-D2 group, 91) and 117 in the control group (CME control group, 72; D2 control group, 45). There was a significantly higher proportion of overweight patients (BMI ≥24 kg/m 2) in the RELARC-CME than in the CME control group (67.1% [55/82] vs. 33.3% [24/72], χ 2=17.469, P<0.001). There were no other statistically significant differences in baseline characteristics (all P>0.05). No significant disparities were found between the CME and D2 groups in terms of operation duration, intraoperative blood loss, rate of conversion to open surgery, combined organ resection, intraoperative blood transfusion, or intraoperative complications (all P>0.05). There was a trend toward Clavien–Dindo grade II or higher postoperative complications in the RELARC-CME group (24.4% [20/82]) than in the CME control group (18.1% [13/72]); however, this difference was not statistically significant (χ 2=0.914, P=0.339). Similarly, the difference in this rate did not differ significantly between the RELARC-D2 group (25.3% [23/91]) and D2 control group (24.4% [11/45], χ 2=0.011, P=0.916). The median duration of postoperative follow-up was significantly shorter in the RELARC groups than in the corresponding control groups. Specifically, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-CME and 7.2 (6.0, 9.0) months in the CME control group ( Z=-10.608, P<0.001). Similarly, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-D2 group as opposed to 8.3 (6.6, 9.0) months in the D2 control group ( Z=-10.595, P<0.001). The 3-year DFS rate (91.5%) and OS rate (96.3%) tended to be higher in the RELARC-CME group than in the CME control group (84.7% and 90.3%, respectively). The 3-year DFS rate (87.9%) and OS rate (96.7%) tended to be higher in the RELARC-D2 group than in the D2 control group (81.8% and 88.6%, respectively); however, these differences were not statistically significant (all P>0.05). Subgroup analysis according to pathological stage revealed that patients in the RELARC-D2 group with pN0 stage achieved a significantly superior 3-year OS rate than did those in the D2 control group (100% vs. 88.9%, P=0.008). We identified no statistically significant differences in survival rates between the remaining subgroups (all P>0.05). Conclusions:A high-quality surgical clinical trial with close follow-up can achieve perioperative safety and a trend toward improved survival outcomes.

OBJECTIVE To prepare a self-microemulsifying drug delivery system(SMEDDS) for the oral administration of nebivolol hydrochloride(NBH) and to conduct in vitro evaluation. METHODS The solubility of NBH was determined using various oil phases, surfactants, and co-surfactants. The composition of the blank self-microemulsifying formulation was determined using pseudo-ternary phase diagrams. A centralcomposite design-response surface method was employed to screen and optimize the formulation variables, and an excess amount of NBH raw material was incorporated to determine the drug loading capacity. RESULTS The optimized composition of the NBH-SMEDDS formulation consisted of medium-chain glycerides, capryl caproyl macrogol glycerides, and 2-(2-ethoxyethoxy) ethyl acetate at a ratio of 20∶48∶32, with a drug loading capacity of 20.05 mg. The particle size, self-emulsification time, and particle size distribution range of the formulation were in agreement with the predicted values. Dissolution testing demonstrated that the overall dissolution trend of NBH-SMEDDS in the medium was higher than that of NBH powder and NBH ordinary tablet. The stability of NBH-SMEDDS was found to be satisfactory under accelerated conditions for 1, 2, and 3 months. CONCLUSION The SMEDDS shows potential for enhancing the in vitro dissolution of NBH and demonstrates good stability.

OBJECTIVE To solve the problem of insolubility of itraconazole, improve its dissolution in vitro, and provide a reference for further industrial scale-up of the itraconazole multiparticle system. METHODS Itraconazole multiparticle system pellets were dissolved in an organic solvent and prepared in a fluidized bed by bottom spraying. Itraconazole and hydroxypropyl methylcellulose were sprayed onto the surface of the sucrose pellet core to form a uniform solid dispersion. The preparation parameters of the fluidized bed bottom spray coating were investigated by single factor method. The mass ratio of drug to carrier and core weight gain of the itraconazole multiparticle system were optimized by central composite design and response surface methodology with accumulative dissolution rate, application efficiency and adhesion rate as response values. Samples were prepared to verify the optimized prescription, the microscopic hierarchical structure of the itraconazole multiparticle system was observed by scanning electron microscope, and the solid dispersion in the itraconazole multiparticle system pellets was characterized by differential scanning calorimetry(DSC) and X-ray diffraction(XRD). The dissolution curves of itraconazole pellets and the physical mixture in 0.1 mol·L−1 HCl dissolution medium were compared to verify the solubilization effect. RESULTS Single factor method was used to determine the bottom spray coating parameters of the fluidized bed. The pumping speed was set as 3.0−5.0 mL·min−1, the atomization pressure was set as 1.5 bar, the inlet air volume was set as 110 m3·h−1, and the material temperature was set as 35 ℃. According to the central composite design and response surface methodology, the mass ratio of drug to carrier of the optimized prescription was 1∶1.5 and the core weight of the pill was 75%, and the response values reached the expected value. The result of scanning electron microscopy showed that the diameter of the itraconazole multiparticle system pellet was about 910 µm, the diameter of the sucrose pellet core was about 570 µm, the thickness of the drug loading layer was about 110 µm, and the thickness of encapsulation layer was about 11 µm. The results of DSC and XRD showed that itraconazole formed a uniform solid dispersion in the itraconazole multiparticle system pellets, which was amorphous. In the dissolution medium of 0.1 mol·L−1 HCl, the accumulative dissolution rate of the multiparticle system after 90 min was about 10 times that of the physical mixture, which showed that the solubilization effect was remarkable. CONCLUSION The dissolution of itraconazole in vitro can be significantly improved by processing itraconazole into pellets with multiparticle system and forming solid dispersion.

Objective:To study the clinical and genetic features of neonatal Schaaf-Yang Syndrome (SYS).Methods:The clinical data of a newborn with SYS admitted to our hospital in October 2022 were retrospectively analyzed. Using "Schaaf-Yang syndrome", "newborn", "preterm", "neonate" as keywords, we searched the CNKI, Wanfang Database, VIP database, Chinese Medical Journal Full Text Database, PubMed, Embase, Web of Science and the Cochrane Library for literature published during the date of establishment to March 24th, 2023. The clinical and genetic features of neonatal SYS from published literature were summarized.Results:The patient in this case was a female preterm infant with a gestational age of 33 +3 weeks, characterized by epiglottic collapse, hypotonia, poor response, weak sucking and swallowing, respiratory failure, and abnormalities such as bilateral low ear position and short limbs. The patient received symptomatic treatment, often failed to withdraw the ventilator, and had difficulty intubating. Meanwhile, whole exome sequencing identified a de novo truncated variant c.2892del (p.Trp965Glyfs*3) in the MAGEL2 gene of the patient. At 30 d after birth, the patient died after giving up treatment by her family. A total of 11 retrieved literatures had neonatal records, including 17 cases. The clinical features involved joint contracture (15/17), hypotonia (14/17), respiratory failure (12/17), and feeding difficulties (12/17). Most of the gene variation was truncated mutation, and only 1 heterozygote deletion mutation was found. These gene variation included c.1996dupC(p.Gln-666Profs*47) variation in 7 cases, c.1912C>T(p.Q638X) variation in 3 cases, c.1996C>T(p.Q666*) in 1 case, c.2847-2883del37 in 1 case, c.2118delT(p.Leu708Trpfs*7) in 1 case, c.1850G>A(p.RP617*) in 1 case, c.2167delG (p.Ala723Profs*4) in 1 case, c.2005C>T(p.Gln669) in 1 case, c.2892del(p.Trp965Glyfs*3) in 1 case, respectively. Conclusions:The main manifestations of neonatal SYS included hypotonia, feeding difficulties, respiratory failure and joint contracture. Most of the mutations were truncated mutations of c.1996dupC (p.Gln-666Profs*47).

ObjectiveCongenital heart disease （CHD） is a common birth defect in children， with its incidence increasing annually. Because of their special health status， the vaccination situation for children with CHD has become a focal point of attention. This paper systematically reviews the current status of vaccination among children with CHD in China to identify existing issues in vaccination efforts for children with CHD， provide guidance for increasing vaccination rates among children with CHD， reduce the incidence of vaccine-preventable diseases， and provide ideas for subsequent research. MethodsLiterature on the vaccination of children with CHD in China was searched in both Chinese and English databases， including CNKI， Wanfang Data Knowledge Service Platform， VIP， Chinese Biomedical and Web of Science， PubMed， EmBase， and the Cochrane Library. Relevant literature was identified based on inclusion and exclusion criteria， and data extraction was carried out to summarize the research results. ResultsA total of 15 studies were included. Three articles focusing on expert consensus （guideline recommendations） for vaccination of children with CHD in China all agreed that vaccination is both feasible and necessary for children with CHD. Systematic analysis found that the overall timely vaccination rate for children with CHD was between 34% and 50%， with a notable delay in vaccination. However， after professional outpatient assessment， the vast majority of children with CHD were advised to be vaccinated according to the national recommended schedule， with only about 2% of them being advised to delay vaccination. The proportion of children with CHD who reported suspected adverse events following immunization （AEFI） was low and not significantly different from that of healthy/control children. ConclusionThe safety of vaccinations for children with CHD in China is relatively high， but the total timely vaccination rate is currently low. In order to improve the coverage and timeliness of vaccination in children with CHD， it is recommended that relevant departments provide vaccination policy support. There is a lack of research on the effectiveness of vaccination in children with CHD， so further studies are urgently needed to further improve the vaccination strategy for children with CHD in China.

Alginate composite hydrogel is one of the research hotspots of tumor drug delivery system materials at present. Alginate hydrogel has good biocompatibility and regeneration properties. However, the natural alginate saline gel may not achieve the expected results in the body environment due to the slow degradation and instability of the gel. Alginate has found extensive application in cancer therapy through its combination with other materials and the utilization of ionic cross-linking, covalent cross-linking, and free radical polymerization to form hydrogels. Based on the composite system of alginate brine gel, this paper summarizes the structure and properties of alginate hydrogel, with a focus on recent research into alginate composite hydrogel in common cancer treatments application, summarizes the current research focus and discuss the existing problems of alginate composite hydrogel, so as to provide reference for further expanding the research of alginate composite hydrogel in clinical cancer treatment.

Objective:To investigate the prognostic significance of D-dimer level in patients with diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of 70 newly diagnosed DLBCL patients who were admitted to Tianjin People's Hospital from January 2015 to June 2019 were retrospectively analyzed. The optimal cut-off value of D-dimer for survival was determined according to the receiver operating characteristic (ROC) curve, and the patients were grouped. The differences of coagulation related indexes and clinicopathological features between patients with different D-dimer levels were compared. Kaplan-Meier method was used for univariate analysis of overall survival (OS), and Cox regression model was used for multivariate analysis of OS.Results:According to ROC curve, the best cut-off value of D-dimer for survival was 0.75 mg/L. The proportion of patients with different clinical staging, international prognostic index score, lactate dehydrogenase level had statistically significant differences between the D-dimer ≥0.75 mg/L group (36 cases) and <0.75 mg/L group (34 cases) (all P < 0.05). The prothrombin time of D-dimer ≥ 0.75 mg/L group and < 0.75 mg/L group were (13.5±0.9) s and (13.0±0.8) s, respectively, and the activated partial thromboplastin time were (37±5) s and (34±6) s, respectively,and the differences were statistically significant (all P < 0.05). Univariate analysis showed that the 5-year OS rates of DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ, international prognostic index score > 2, lactate dehydrogenase level > 240 U/L, B symptoms, D-dimer level ≥0.75 mg/L were decreased (all P < 0.05). Multivariate Cox regression analysis showed that D-dimer ≥0.75 mg/L was an independent risk factor for OS of DLBCL patients ( HR=0.368, 95% CI 0.144-0.944, P= 0.038). Conclusion:The level of D-dimer can be used as a clinical indicator to judge the prognosis of DLBCL patients, and the prognosis of patients with high D-dimer level is poor.

Objective:To investigate the effect of exercise both before and after myocardial infarction (MI) on microvessel density in the left ventricle, and on the mRNA and protein expression of vascular endothelial growth factor (VEGF) and its receptors.Methods:Ninety-six male Sprague-Dawley rats were randomly divided into a sedentary sham operation group (Sed-Sh), a pre-MI exercise sham operation group (PreE-Sh), a sedentary MI group (Sed-MI), a pre-MI exercise group (PreE-MI), a post-MI exercise group (PostE-MI) and a combined exercise group (ComE-MI). The rats of the exercise groups underwent 60min of treadmill training daily five times a week for five weeks, while those of the Sed-Sh and Sed-MI groups remained sedentary. Then all of the rats underwent either an operation to induce an acute MI (Sed-MI, PreE-MI, PostE-MI and ComE-MI groups) or a sham MI operation (Sed-Sh and PreE-Sh groups). Four weeks after the operation, the exercise groups underwent five days adaptive training, followed by 8 weeks of 60min of treadmill training daily, five times a week. All of the rats were then sacrificed. The microvessel densities in the infarcted and uninfarcted volumes were detected using Factor VIII-related antigen staining, while the mRNA expressions of VEGF and its receptors were examined using a real-time polymerase chain reaction. The protein expressions of VEGF and its receptors were measured using western blotting.Results:Compared with Sed-MI group, the average microvessel densities of the PostE-MI and ComE-MI groups had increased significantly, with the average density of the PostE-MI group significantly higher than that of the PreE-MI group, but significantly lower than the ComE-MI group′s average. Compared with the Sed-MI group, the average mRNA expression of VEGF and its receptors in the PostE-MI and ComE-MI groups was significantly higher, without significant differences between the two groups.Conclusions:Pre-MI exercise does not significantly improve left ventricular function or microvessel density, while post-MI exercise does, as it can upregulate the expression of VEGF and its receptors to activate VEGF signaling. The increase in microvessel density may benefit left ventricular remodeling and cardiac function.

Nanocrystals are nanoscale (1-1000 nm) dispersion systems in which small numbers of surfactants or polymers are used as stabilizers to disperse insoluble drug particles in water or oil. Nanocrystals enjoy not only high drug content, but also a simple and mature preparation process. At present, 24 nanocrystals products that have been marketed mainly focus on enhancing the solubility and bioavailability of poorly soluble drugs. And recent years have witnessed an increasing number of research reports on target drug delivery of nanocrystals through particle size control and surface modification. This paper mainly introduces three targeting strategies for prolonging the in vivo circulation time of nanocrystals, increasing the affinity for tumor cells and achieving the response to internal and external stimuli, and discusses the current challenges in the application of nanocrystal technology to targeted anti-tumor drugs.