Multi-conjugate vaccine and polyvalent vaccine can reduce the number of vaccinations, improve vaccination efficiency, and provide wider protection against diseases, and can not only brings convenience to recipients but also reduce healthcare costs, making it a key focus in modern vaccine development. However, even if the components of the vaccine are derived from already approved monovalent vaccines, it must still be considered as a new vaccine and undergo randomized controlled clinical trials to evaluate their safety and efficacy in humans. Due to the inclusion of multiple antigens, clinical evaluation must consider the potential interactions between or among the components, as well as the impacts of adjuvants, preservatives, and other ingredients on the vaccines' safety and efficacy. These factors introduce certain specific challenges in the clinical evaluation of multi-conjugate vaccine and polyvalent vaccine. This article summarizes the key elements and methods of clinical study design for multi-conjugate vaccine and polyvalent vaccine in terms of safety, immunogenicity, and protective efficacy, and discuss the problems and challenges exisitng in vaccine clinical evaluation to provide reference for the standardization of clinical study design of multi-conjugate vaccine and polyvalent vaccine.

The impact of vaccines on public health and their effectiveness in controlling infectious diseases partly depends on their coverage rate, which refers to the proportion of individuals vaccinated within a specific population. Vaccination coverage is foundational data for vaccine immunization programs, a key parameter for evaluating and monitoring the implementation of vaccination plans, and an important data point in real-world post-market studies of vaccines. Additionally, research on vaccination coverage is becoming increasingly prevalent in vaccine evaluation, primarily used to establish the risk of disease incidence in populations with different vaccination coverage rates in order to assess the protective effectiveness of vaccines. This paper reviews the research methods used to assess vaccine coverage both domestically and internationally, as well as their applications in evaluating vaccine effectiveness. It also analyzes and compares the advantages and disadvantages of different research methods for measuring vaccination coverage and discusses the significance of monitoring and improving vaccine coverage rates. The goal is to promote research and application of vaccination coverage rates in China, providing a scientific basis for post-market vaccine studies and for local administrative departments to formulate immunization policies.

Multi-conjugate vaccine and polyvalent vaccine can reduce the number of vaccinations, improve vaccination efficiency, and provide wider protection against diseases, and can not only brings convenience to recipients but also reduce healthcare costs, making it a key focus in modern vaccine development. However, even if the components of the vaccine are derived from already approved monovalent vaccines, it must still be considered as a new vaccine and undergo randomized controlled clinical trials to evaluate their safety and efficacy in humans. Due to the inclusion of multiple antigens, clinical evaluation must consider the potential interactions between or among the components, as well as the impacts of adjuvants, preservatives, and other ingredients on the vaccines' safety and efficacy. These factors introduce certain specific challenges in the clinical evaluation of multi-conjugate vaccine and polyvalent vaccine. This article summarizes the key elements and methods of clinical study design for multi-conjugate vaccine and polyvalent vaccine in terms of safety, immunogenicity, and protective efficacy, and discuss the problems and challenges exisitng in vaccine clinical evaluation to provide reference for the standardization of clinical study design of multi-conjugate vaccine and polyvalent vaccine.

The impact of vaccines on public health and their effectiveness in controlling infectious diseases partly depends on their coverage rate, which refers to the proportion of individuals vaccinated within a specific population. Vaccination coverage is foundational data for vaccine immunization programs, a key parameter for evaluating and monitoring the implementation of vaccination plans, and an important data point in real-world post-market studies of vaccines. Additionally, research on vaccination coverage is becoming increasingly prevalent in vaccine evaluation, primarily used to establish the risk of disease incidence in populations with different vaccination coverage rates in order to assess the protective effectiveness of vaccines. This paper reviews the research methods used to assess vaccine coverage both domestically and internationally, as well as their applications in evaluating vaccine effectiveness. It also analyzes and compares the advantages and disadvantages of different research methods for measuring vaccination coverage and discusses the significance of monitoring and improving vaccine coverage rates. The goal is to promote research and application of vaccination coverage rates in China, providing a scientific basis for post-market vaccine studies and for local administrative departments to formulate immunization policies.

Objective:To investigate the clinicopathological characteristics and prognostic factors of gastrointestinal stromal tumor (GIST) with initial surgical resection.Methods:The retro-spective cohort study was conducted. The clinicopathological data of 847 GIST patients who under-went initial surgical resection in Tianjin Medical University Cancer Institute & Hospital from January 2011 to December 2020 were collected. There were 405 males and 442 females, aged (60±10)years. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the nonparameter rank sum test. The Kaplan-Meier method was used to calculate survival rates. Univariate analysis was conducted using the Log-rank test. Multivariate analysis was conducted using the COX regression model. Results:(1) Clinicopatholo-gical characteristics. Of 847 patients, the tumor primary location was stomach in 585 cases, jejunum and ileum in 142 cases, duodenum in 76 cases, colorectum in 10 cases, esophagus in 3 cases, and extra-gastrointestinal in 31 cases. There were 13 cases with liver metastasis and 22 cases with abdominal metastasis. The tumor maximum diameter was (7±5)cm, and the number of nuclear divisions was 4(range, 0-60) cells/50 high-power field or 5 mm 2. According to risk classification of National Institutes of Health (NIH), 31 cases were of extremely low risk, 238 cases were of low risk, 213 cases were of moderate risk, 365 cases were of high risk. There were 839 of 847 patients positive for CD117, 788 cases positive for Dog-1, 710 cases positive for CD34, respectively. There were 272 cases with Ki-67 <5%, 214 cases with Ki-67 of 5%- 9%, 198 cases with Ki-67 ≥10%, 163 cases with missing data. R 0 resection was in 814 cases and non-R 0 resection was in 33 cases. (2) Gene testing and postoperative adjuvant therapy of GIST patients. ① Gene testing. Of 847 patients, 424 underwent genetic testing. The proportion of genetic testing was 1.89%(1/53) in 2011, 9.76%(8/82) in 2012, 8.45%(6/71) in 2013, 15.66%(13/83) in 2014, 50.00%(40/80) in 2015, 55.26%(42/76) in 2016, 73.86%(65/88) in 2017, 68.27%(71/104) in 2018, 80.65%(75/93) in 2019, 88.03%(103/117) in 2020, respectively. Of 424 with genetic testing, 338 cases had KIT mutation, 31 cases had PDGFRA mutation, 55 cases were wild type. ② Adjuvant therapy. Of 847 patients, 253 patients underwent postoperative adjuvant therapy. The proportions of postoperative adjuvant therapy were 8.82%(21/238), 41.78%(89/213), 39.18%(143/365) in patients of low risk, moderate risk, high risk. Of 578 patients with moderate to high risk, the proportion of postoperative adjuvant therapy was 15.15%(5/33) in 2011, 14.71%(10/68)in 2012, 22.45%(11/49) in 2013, 29.09%(16/55) in 2014, 41.38%(24/58) in 2015, 46.15%(24/52) in 2016, 32.81%(21/64)in 2017, 60.00%(45/75) in 2018, 60.42%(29/48) in 2019, 61.84%(47/76) in 2020, respectively. Of 253 patients underwent postoperative adjuvant therapy, 247 cases received imatinib had 6 cases received sunitinib. (3) Comparison of clinicopathological characteristics of GIST with non-gastric origin and gastric origin. Of 847 patients, 262 cases had non-gastric origin and 585 cases had gastric origin. There were significant differences in gender, the number of tumor, tumor maximum diameter, Ki-67 index, risk classification of NIH, and R 0 resection between the two groups ( χ2=8.62, 8.40, 12.97, 6.57, Z=-6.15, χ2=17.19, P<0.05). (4) Analysis of influencing factors for recurrence-free survival rate in GIST patients. Results of multivariate analysis showed that the year of initial diagnosis, primary site, tumor maximum diameter, mitotic image, risk classification of NIH, R 0 resection, genetic testing and postoperative adjuvant therapy were independent factors influencing recurrence-free survival rate in GIST patients with initial surgical resection ( hazard ratio=0.58, 0.61, 2.00, 1.71, 5.81, 2.56, 0.65, 0.38, 95% confidence interval as 0.39-0.85, 0.45-0.83, 1.46-2.74, 1.24-2.35, 3.16-10.69, 1.63-4.02, 0.46-0.94, 0.25-0.56, P<0.05). Conclusions:GIST with initial surgical resection is common located in stomach, with high positive rate in CD117 and Dog-1. The number of people undergoing genetic testing and targeted therapy for GIST is increasing year by year. There are significant differ-ences in clinicopathological characteristics between GIST with non-gastric origin and gastric origin. The year of initial diagnosis, primary site, tumor maximum diameter, mitotic image, risk classifica-tion of NIH, R 0 resection, genetic testing and postoperative adjuvant therapy are independent factors influencing recurrence-free survival rate in GIST patients with initial surgical resection.

Circulating tumor cells(CTCs)are cells that dissociate from the tumor tissue and enter the lymphatic system or bloodstream with close association with tumor metastasis and recurrence.CTCs contain complete pathological information,which can be extracted by isolation,enrichment,and analysis of the CTCs to guide cancer diagnosis and treatment,thereby significantly improving the monitoring efficiency and prognosis of cancer.Compared with tissue biopsy,liquid biopsy with CTCs as a biomarker enables specific and dynamic detection of tumor growth with a less painful experience.For detection of CTCs,the cells must be captured from body fluids,followed then by their release and enrichment.This review summaries the latest research progress in responsive isolation of CTCs(e.g.with light,dielectrophoresis,acoustophoresis and magnetophoresis),chemical isolation(specific molecules and topological structure)and responsive release(e.g.,light,electric,thermal,pH,enzyme responsiveness,and substrates break).Responsive isolation utilizes the differences in physical properties between CTCs and blood cells,while chemical isolation utilizes specific recognition mechanisms to capture the CTCs.These techniques result in low cell damage with a high specificity to facilitate further analysis.Currently,CTC detection has been applied for early diagnosis and prognostic assessment of multiple cancers including lung cancer,liver cancer,colorectal cancer,and prostate cancer.

Circulating tumor cells(CTCs)are cells that dissociate from the tumor tissue and enter the lymphatic system or bloodstream with close association with tumor metastasis and recurrence.CTCs contain complete pathological information,which can be extracted by isolation,enrichment,and analysis of the CTCs to guide cancer diagnosis and treatment,thereby significantly improving the monitoring efficiency and prognosis of cancer.Compared with tissue biopsy,liquid biopsy with CTCs as a biomarker enables specific and dynamic detection of tumor growth with a less painful experience.For detection of CTCs,the cells must be captured from body fluids,followed then by their release and enrichment.This review summaries the latest research progress in responsive isolation of CTCs(e.g.with light,dielectrophoresis,acoustophoresis and magnetophoresis),chemical isolation(specific molecules and topological structure)and responsive release(e.g.,light,electric,thermal,pH,enzyme responsiveness,and substrates break).Responsive isolation utilizes the differences in physical properties between CTCs and blood cells,while chemical isolation utilizes specific recognition mechanisms to capture the CTCs.These techniques result in low cell damage with a high specificity to facilitate further analysis.Currently,CTC detection has been applied for early diagnosis and prognostic assessment of multiple cancers including lung cancer,liver cancer,colorectal cancer,and prostate cancer.

This paper discusses the theoretical basis of traditional Chinese medicine （TCM） for the treatment of cancer-related fatigue （CRF） based on the principle of treating overstrain with warming in the Huangdi's Internal Classic 《黄帝内经》 and the role of hypothalamic-pituitary-adrenal （HPA） axis dysregulation in CRF， aiming to provide new ideas for the clinical treatment of CRF. In the pulsatile regulation of the HPA axis， cortisol， which is synthesized and released by the adrenal cortex， plays an essential role in the life activities. The abnormal circadian rhythm and reduced serum level of cortisol are major factors leading to CRF. Therefore， increasing the serum level and stimulating the biological activity of cortisol and restoring the normal function of HPA axis are important targets for the treatment of CRF and also the key to the TCM treatment of this disease. According to the TCM principle of treating overstrain with warming， we interpreted the etiology and clinical manifestations of overstrain and further explored the causes of CRF. It is believed that the depletion of Qi and blood， Yin and Yang， and fluid in the kidney， spleen， and liver is the key of the disease， which results in symptoms such as fatigue. Further， we elaborated on the theoretical connotation of warming and summarized the two main treatment principles of tonifying with warm-natured herbs and relieving fever with sweet- and warm-natured herbs. According to the different characteristics of the organs affected by pathogen， we proposed the treatment method of warming kidney to cultivate essence， warming stomach and nourishing spleen to replenish Qi， nourishing liver and tonifying blood to promote Qi movement， and relieving fever with sweet- and warm-natured herbs to alleviate fatigue. The warming method can elevate the serum level and invigorate the biological functions of cortisol in CRF patients， which provides a new theoretical basis for alleviating the symptoms and improving the quality of life of cancer patients in clinical practice.

Objective: To effectively reduce the concentration of poisons in cleanroom, protect the health of workers, realize the optimization and automatic control of the new return air device. And the influence of initial concentration, air volume, temperature and relative humidity of formaldehyde on the purification effect of the new return air device was explored. Methods: The purification effect of the new return air device installed with the activated carbon and the photocatalyst purification net or ordinary activated carbon purification network was tested in a 60 m³ simulated cleanroom. The concentration of formaldehyde was determined by solution absorption-phenol reagent spectrophotometry. Based on the single factor experiment to determine the combination of two purification nets. The effects of air volume, initial formaldehyde concentration, temperature and relative humidity on the purification effect of the new return air device were investigated by orthogonal test. Then, the performance parameters of the return air device to purify formaldehyde were determined. Results: The formaldehyde purification efficiency of the two types of purification nets in the new return air device was higher than that of the ordinary activated carbon purification network (P<0.05) . The combination of activated carbon and photocatalyst purification net has no effect on the formaldehyde purification efficiency of the return air device (P>0.05) . According to the direct analysis and variance analysis, air volume was the most sensitive factor (F value is 18.894, P<0.05) , followed by initial concentration (F value is 16.128, P<0.05) , while temperature and relative humidity have little effect (F value is 0.041 and 0.599, respectively, P>0.05) . LSD analysis showed that there was no significant difference in the purification efficiency of formaldehyde between 475 m³/h and 626 m³/h (P>0.05) . From the perspective of formaldehyde purification efficiency and energy saving, when the air volume is set to 475 m³/h, the new return air device has higher purification efficiency for high concentration of formaldehyde. Conclusion The new return air device consisting of activated carbon and photocatalyst purification net can play a good purification role in cleanroom with different temperatures and different humidity. Its formaldehyde purification efficiency is affected by air volume and initial concentration.

Objective: To analyze the epidemiological characteristics and pathogen types of viral diarrhea in children under 5 years of age in Shandong province, and provide reference for the prevention and control of viral diarrhea. Methods: A total of 1 017 fecal samples were collected from all children aged 5 years and younger with diarrhea who were admitted to the sentinel hospital of Shandong province from 2012 to 2017 within 3 days. Rotavirus antigen was detected by using an ELISA method . Rotavirus G/P typing was performed by RT-PCR; Norovirus (GI and GII), Sapovirus, and Astrovirus were detected by multiplex RT-PCR, and adenovirus was detected by PCR. Results: In the 1 017 fecal specimens, the overall positive rate was 51.62% (525/1017), and viral nucleic acids were detected in at least 421 samples, and mixed virus infection was found in 104 sampes. The mixed infection accounted for 10.23% (104/1017) of all infections. The positive detection rates of Rotavirus, Calicivirus, Adenovirus and Astrovirus were 34.22% (348/1017), 16.91% (172/1017), 2.56% (26/1017), and 9.64% (98/1017)). The total detection rate of diarrhea virus and the detection rate of Rotavirus were the highest at 12 to 17 months of age, which was 51.72% (105/203) and 20.20% (41/203), respectively. The positive rate of diarrhea in children aged 2 years and younger was 49.36% (502/1017), which was much higher than the positive rate of diarrhea in children over 2 years old (2.26% (23/1017)). The peak of viral diarrhea was found to occur between November and April of the following year. The genotype of rotavirus was dominated by G9 (82.76%), the P genotype was dominated by P[8] (80.46%), and the G/P combination was dominated by G9P[8] (83.87%). Norovirus was the main infection in the Calicivirus (87.21%). Conclusions From 2012 to 2017, viral diarrhea in children under 5 years of age in Shandong Province was mainly caused by Rotavirus infection, followed by Norovirus. The overall prevalence of viral diarrhea in Shandong was moderate in China, and autumn and winter were the main epidemic season for viral diarrhea.