ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

The blood-brain barrier(BBB)is a semi-permeable biological barrier between brain tissue and plasma,however,its physical,enzymatic and immune properties,as well as its unique transport mechanism severely limit the entry of therapeutic drugs and diagnostic agents into the brain,which poses great challenges for the prevention and treatment of brain diseases.Hence,this review summarizes and discusses the complex structural components and various transport mechanisms of BBB,and interprets the difficulties and feasible ways of drug delivery across BBB.Furthermore,the latest research progress and future development trends of various delivery systems for brain drug delivery are introduced and discussed to provide references for further perfecting their design and driving their transformation.Finally,this review discusses the pathological changes of BBB in brain diseases and the design of drug delivery strategies for pathological BBB.Collectively,this review highlights the design and optimization of drug delivery strategies across the BBB based on nano-delivery system and provides accessible guide for current opportunities and challenges of intracerebral drug delivery.

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.

Gei Herba is a traditional folk herbal medicine with a variety of functions such as replenishing Qi and invigorating spleen， tonifying blood and nourishing Yin， moistening lung and resolving phlegm， activating blood and alleviating edema， moving Qi， and activating blood. The reports about the pharmacological effects of this herbal medicine have been increasing in recent years. By reviewing the ancient and modern literature about Gei Herba， we systematically organized the name， original plants， nature， taste， and functions of this herbal medicine， and summarized the modern pharmacological studies and clinical applications of Gei Herba in cardiovascular and cerebrovascular diseases. Gei Herba was first recorded in the name of "Dijiao" in the Geng Xin Yu Ce（《庚辛玉册》） written in the Ming Dynasty. It is derived from Geum japonicum var. chinense （Rosaceae） and sometimes confused with Adina rubella （Rubiaceae）. This medicine had numerous synonyms in the local materia medica books. Gei Herba is widely distributed and harvested in summer and autumn， with the dried whole grass used as medicine. The historical records of the nature， taste， meridian tropism， main functions， and indications of Gei Herba are not consistent. It is generally believed that Gei Herba is pungent， bitter， sweet， cool， and has tropism to the liver， spleen， and lung meridians. Based on the effects of tonifying Qi， activating blood， and nourishing Yin， modern pharmacological studies have reported that the extracts of Gei Herba and the tannin phenolic acid compounds and triterpenoids isolated from Gei Herba have therapeutic effects on cardiovascular and cerebrovascular diseases such as hypertension， myocardial ischemia， cerebral ischemia， and vascular dementia. This study provides a reference for discovering the clinical advantages of Gei Herba and developing new drugs.

Objective : Cas9-RNP biomimetic nanoparticles cas9-RNP@ MMs were prepared by encapsulating the Cas9 Ribonucleoprotein complex (RNP) using mouse macrophage membranes，with the aim of utilizing this biomimetic nanoparticle to deliver the Cas9-RNP complex for gene editing ，and further study the endocytosis of Cas9- RNP@ MMs and its gene editing effect in mouse macrophage RAW264. 7 in vitro ，providing evidence for the development oflow-toxicity biomimetic nanoparticle carriers that inhibit NLRP3 therapeutic targets． Methods : The purified mouse macrophage membrane was mixed with the prepared cas9-RNP mixture，and after ultrasound，the CAS9- RNP@ MMS was obtained by liposome extrusion instrument ; The particle size of Cas9-RNP@ MMswas measured by nanoparticle tracking analysis，and the particle morphology of Cas9-RNP@ MMs was observed under transmission electron microscope．Laser confocal Fluorescence microscope imaging was used to analyze the endocytosis Cas9-RNP @ MMs．The Biocompatibility of Cas9-RNP@ MMs was measured by MTT assay．The expression of NLRP3 was detected by qPCR and Western blot to verify the knockdown effect of Cas9-RNP@ MMs on NLRP3 gene. Results: The average particle diameter of Cas9-RNP@ MMs prepared from macrophages was about 216 nm．Under laser confocal fluorescence microscope，the Cas9-RNP@ MMs could be successfully endocysed by Raw246. 7 cell．MTT assay indicated that the Cas9-RNP@ MMs-treated mouse macrophage RAW246. 7 had good biocompatibility．qPCR and Western blot showed that two NLRP3-specific guide RNA were mediated by Cas9-RNP@ MMs，with good effect of knockdown NLRP3 gene expression． Conclusion Nano-scale vesicles Cas9-RNP@ MMs loaded with Cas9-RNP complexes were successfully prepared by biomimetic nanoparticles． Cas9-RNP@ MMs have good biocompatibility and can be efficiently endocytosed by RAW246. 7 cells．Cas9-RNP@ MMs containing NLRP3-specific sgRNA can specifically knock down NLRP3 gene expression.

Objective: To evaluate the quality of tandem mass spectrometry (MSMS) screening for neonatal inherited metabolic diseases in Zhejiang Province from 2009 to 2021. Methods: The data pertaining to MSMS screening for neonatal inherited metabolic diseases in Zhejiang Province from 2009 to 2021 were collected from the database created by Zhejiang Provincial Center for Neonatal Disease Screening. The percentage of MSMS screening, percentage of recall of suspected screening-positive infants and incidence of neonatal inherited metabolic diseases were analyzed retrospectively to evaluate the quality of MSMS screening for inherited metabolic diseases. Results: A total of 4 706 916 newborns were screened among 8 297 039 live births by MSMS in Zhejiang Province from 2009 to 2021, and the percentage of MSMS screening increased from 5.48% to 97.54%, with a mean percentage of 56.73%. Of 46 838 suspected screening-positive infants, 45 527 infants were recalled, and the percentage of recall increased from 94.57% to 98.62%, with a mean percentage of 97.20%. A total of 1 038 infants were definitively diagnosed with inherited metabolic diseases in Zhejiang Province from 2009 to 2021, with an overall incidence rate of 1/4 535, and the incidence rates of amino acid metabolic disorder, fatty acid oxidation metabolic disorder and organic acid metabolic disorder were 1/11 767, 1/13 763 and 1\15 902, respectively. Of the 11 cities in Zhejiang Province, the highest percentage of tandem mass spectrometry screening for inherited metabolic diseases was found in Hangzhou City (83.01%), and the highest percentage of recall of suspected screening-positive infants was se en in Zhoushan City (99.08%). Conclusions A high percentage of MSMS screening for neonatal inherited metabolic diseases was observed in Zhejiang Province from 2009 to 2021; however, there was a region-specific percentage of screening, and the recall of suspected screening-positive infants remains to be improved.

Abstract Transport of filter paper-dried blood spot samples is a critical procedure during the screening of neonatal inherited metabolic diseases, which is of great significance for the screening accuracy. In order to ensure the timing and safety of sample transport, the cold chain positioning system was initiated by Zhejiang Provincial Center for Quality Control of Neonatal Disease Screening since March 2015. Based on the framework of neonatal disease screening information management system, the function of the logistics transport management system was included in this positioning system, with aims to achieve the monitoring and tracking of sample transport processes through real-time positioning of the sample transport box via China Unicom 4G logistics card and global positioning system/BeiDou Navigation Satellite System. The samples are maintained in a transport environment at 2 to 8 °C via the temperature-controlled box made of 5 °C phase-changed cold-stored materials and general packet radio service (GPRS) temperature recorders. The mean pretest turnover duration reduced from 8.44 days to 5.03 days following introduction of the cold chain positioning system, and the percentage of timely sample delivery increased from 31.69% to 77.90%, while the withdrawal rate of unqualified samples reduced from 0.12% to 0.08%. The cold chain positioning system meets the requirements of transport of filter paper-dried blood spot samples, which has a high potential in screening of neonatal inherited metabolic diseases.

Objective: To analyze the occurrence features of adverse events following immunization (AEFI) of Seasonal Influenza Vaccines (InfV) used in China, 2015-2018 influenza season. Methods: InfV (including concurrent administered with other vaccines) AEFI data were collected through the Chinese national AEFI information system during 2015.9.1-2018.8.31 (excluding Chinese Hong Kong, Macao and Taiwan data). The vaccine lot release data were collected from National Institutes for Food and Drug Control published database. Time periods of three influenza season were 2015.9.1-2016.8.31, 2016.9.1-2017.8.31, 2017.9.1-2018.8.31. The vaccines used and included in this analysis were trivalent inactivated influenza vaccine (IIV3)-Split, IIV3-Split (Children) and IIV-subnit. The incidence of AEFI were calculated (per 100 000 release doses), and epidemiological characteristic were analyzed using descriptive methodology. Results: A total of 8 464 InfV AEFIs were collected in 2015-2018 influenza season from National AEFI Information System, in which 5 646 were IIV3-split, with the rate of 10.64/100 000 release doses, 2 818 were IIV3-split (Children), with the rate of 9.355/100 000 release doses. The most common symptom was fever (axillary temperature ≥37.1 ℃) within vaccine reactions, with a number of 6 207 cases. In which, there were 3 554 cases with fever (axillary temperature ≥38.6 ℃) and the estimated reporting rate was 4.274/100 000 release doses. In all rare vaccine reactions, the most common diagnosis was anaphylactic rash(442, 0.531/100 000 release doses) and angioedema (70, 0.084/100 000 release doses). Even the rates of serious rare vaccine reactions were low, febrile Convulsion (27, 0.032/100 000 release doses) and Henoch-Schönlein Purpura(HSP) (21, 0.025/100 000 release doses) were relatively common in serious rare vaccine reactions during the study period. Conclusion The estimated rate of rare vaccine reactions related toInfV was relatively low. In all vaccine reactions, fever was the most common symptoms. The most common diagnosis of non-serious rare vaccine reaction were anaphylactic rash and angioedema. The incidence of serious rare vaccine reactions was low.