As one of the most common solid organ malignant tumors in the world， hepatocellular carcinoma has climbed to the fourth place in incidence rate and the second place in mortality in China， which seriously threatens people’s health. Terpenoids are natural active substances widely present in nature， among which sesquiterpenoids are numerous. They exhibit a variety of pharmacological activities， such as anti-tumor， antibacterial， anti-inflammatory， antiviral and antioxidant activities. This article reviews the research progress on the anti-hepatocellular carcinoma mechanism of sesquiterpenes from 2015 to 2024. The results showed that 24 sesquiterpenoids for the treatment of hepatocellular carcinoma have been reported in the literature in the past 10 years， and these compounds have shown potential in treating hepatocellular carcinoma by inhibiting cancer cell proliferation， inducing apoptosis， preventing invasion and metastasis， regulating immunity， and enhancing anti-drug resistance. The mechanism of anti-hepatocellular carcinoma mainly involves three regulatory pathways: phosphatidylinositol 3-kinase/protein kinase B/ mammalian target of rapamycin signaling pathway， nuclear factor kappa-B signaling pathway， and mitochondrial pathway. In the future， it is necessary to continue to explore new anti-hepatocellular carcinoma drugs with high research value， conduct in-depth analysis on the mechanism of synergistic anti-hepatocellular cancer effects of multiple components， targets， pathways， and accelerate the development of finished products in order to be widely used in clinical practice.

OBJECTIVE To analyze the chemical constituents and components absorbed into plasma of the extract of Ardisia crenata and to elucidate its possible pharmacodynamic material basis. METHODS Overall， 12 rats were randomly assigned to the blank group （n＝6） and A. crenata group （n＝6） by the paired comparison method. The drug was administered once daily in the morning and afternoon for three days. Serum samples were prepared from serum after redosing on 4th day. The UPLC-QE-HF-MS/ MS was used to analyze and identify the chemical constituents in A. crenata extract and serum samples. Compound Discoverer 3.0 was employed for retention time correction， peak identification， and peak extraction. According to the secondary mass spectrometry information， the Thermo mzCloud online and Thermo mzVault local databases， referring to the relevant literature and control quality spectrum information were used to preliminarily identify the chemical constituents and components absorbed into plasma of A. crenata. RESULTS A total of 34 compounds were identified from the extract of A. crenata， mainly coumarins， flavonoids， organic acids， amino acids， including bergenin， quercetin， gallic acid， L-pyroglutamic acid， etc. Besides， 5 components absorbed into plasma were identified from serum samples: L-pyroglutamic acid， syringic acid， bergenin， cinnabar root saponin A， and mycophenolic acid. CONCLUSIONS L-pyroglutamic acid， syringic acid， bergenin， cinnabar root saponin A， and mycophenolic acid may act as the pharmacodynamic material basis of A. crenata.

ObjectiveTo investigate the effects and mechanism of Zuogui Jiangtang Tongmai prescription （ZJTP） on human umbilical vein endothelial cells （HUVECs） damaged by high glucose combined with lipopolysaccharide （LPS）. MethodThe survival rate of cells was determined by cell counting kit-8 （CCK-8）， and the level of tumor necrosis factor-α （TNF-α） was determined by enzyme-linked immunosorbent assay （ELISA） to determine the optimal injury concentration and action time of LPS， as well as the optimal action concentration of ZJTP drug-containing serum. HUVECs were divided into a blank control group， a model group， a ZJTP drug-containing serum group， and an SCFA mixed liquid group. ELISA was used to detect the level of endothelin-1 （ET-1）， nitric oxide （NO）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and TNF-α. Western blot was performed to detect the protein expression of G protein-coupled receptor43 （GPR43）， β-suppressor protein-2 （β-arrestin-2）， nuclear factor-κB suppressor α （IκBα）， and nuclear factor κB p65 （NF-κB p65）. The nucleation of NF-κB p65 was observed by immunofluorescence staining （IF）. The role of GPR43 in the regulation of inflammatory injury was observed by means of small interfering ribonucleic acid （siRNA）. The cells after intervention were divided into an empty carrier group， a ZJTP drug-containing serum group， a Si-GPR43 group， and a Si-GPR43 + ZJTP drug-containing serum group. The content of IL-1β， IL-6， and TNF-α was detected by ELISA. The protein expression of pathways was detected by Western blot. IF was used to observe the nucleation of NF-κB p65. ResultThe optimal molding condition was 1 mg·L^-1 LPS for 24 h. The optimal drug intervention condition was 5% ZJTP drug-containing serum for 24 h. Compared with the blank control group， the content of ET-1 in the model group was significantly increased， and the content of NO was significantly decreased （P<0.01）. The levels of inflammatory factors were significantly increased （P<0.01）. The expressions of GPR43 and IκBα were significantly decreased， while the protein expressions of β-arrestin-2 and NF-κB p65 were significantly increased （P<0.01）. NF-κB p65 protein was transferred from the extranuclear to the intranuclear （P<0.01）. Compared with the model group， the content of ET-1 in the ZJTP drug-containing serum group was decreased， and the content of NO was increased （P<0.05）. The levels of inflammatory factors decreased （P<0.05）. The protein expressions of GPR43 and IκBα were increased， while the expressions of β-arrestin-2 and NF-κB p65 were decreased （P<0.05）. The amount of NF-κB p65 transferred from the intranuclear to the extranuclear decreased （P<0.01）. The mechanism study showed that compared with the Si-GPR43 group， the content of IL-1β， IL-6， and TNF-α were significantly decreased after treatment with ZJTP drug-containing serum （P<0.01）. The protein expressions of GPR43 and IκBα were significantly increased （P<0.01）， while the protein expressions of β-arrestin-2 and NF-κB p65 were significantly decreased （P<0.01）. The amount of NF-κB p65 transferred from the extranuclear to the intranuclear decreased （P<0.01）. ConclusionZJTP has a protective effect on HUVECs with high glucose and LPS-induced inflammatory injury， which may be related to the regulation of GPR43/β-arrestin-2/IκBα/NF-κB pathway.

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.

The seamless phase Ⅱ/Ⅲ design integrates independent phase Ⅱ and phase Ⅲ clinical trials into a continuous, phased adaptive clinical trial design. Compared with traditional independent phase Ⅱ and phase Ⅲ clinical trials, the seamless design offers significant advantages in accelerating drug or vaccine development and improving clinical trial efficiency. Currently, the application of this design in anti-tumor drug research is becoming increasingly mature, and it is gradually expanding to clinical trials of vaccines, including the 9-valent human papillomavirus vaccine, sabin strain inactivated polio vaccine, and others. This paper aims to clarify the seamless phase Ⅱ/Ⅲ design concept and offer valuable insights into its implementation. It accomplishes this by presenting a clinical trial example featuring a phase Ⅱ/Ⅲ seamless design for a 9-valent human papillomavirus vaccine. The article delves into the specific considerations and potential challenges related to implementing the seamless design, aiming to provide valuable insights for optimizing vaccine clinical trials within our country.

Objective:To analyze the epidemiological characteristics of norovirus (NoV) acute gastroenteritis (AGE) outbreaks caused by GII.17[P17] variant in China, 2022.Methods:Information and specimens of AGE outbreaks between January and December 2022 were collected. NoV RNA was detected in all specimens by real-time RT-PCR. The viral genome of the positive specimens were amplified, sequenced and analyzed.Results:Between January and December 2022, 360 AGE outbreaks were reported cumulatively, of which 266 outbreaks successfully obtained genotype results. GII.17 [P17] was one of the main genotypes and detected in 34 outbreaks (12.78%, 34/266), with the highest number of outbreaks detected in spring (6 outbreaks in March and 7 outbreaks in May), mainly in childcare facilities and primary schools (61.76%, 21/34). According to the result of NoV genotype analysis in different age groups, 14 strains of GII.17 [P17] in this study belonged to Cluster III b and SC III branch of Cluster III (Kawasaki308) in the capsid region and polymerase region, respectively, and both belonged to the same cluster as the variant strain (GZ41621 strain) that caused the NoV AGE outbreaks in China during the 2014/15 season. Compared to reference strains of Cluster I, Cluster II and Cluster III a, Cluster III b was provided with 22 amino acid mutations in VP1. The main amino acid changes in the subgroup of Cluster III b including the virus strains isolated in this study were at T294I and Q299R of antigen epitope A, an insertion mutation occurred at antigen epitope D, H353Q at the site I of the human histo-blood group antigen receptor binding site. The selection pressure analysis detected a large number of negative selection sites, indicating that negative selection plays an important role in the evolution of VP1 genes.Conclusions:GII.17 [P17] was one of the primary genotypes responsible for NoV diarrhea outbreaks in China in 2022. Phylogenetic analysis had revealed that it still belonged to the same cluster as the novel GII.17 [P17] variant (strain GZ41621) that caused NoV epidemics in China during the 2014/15 season, exhibiting minor amino acid variations at the potential epitope.

Objective:To investigate the impact of short-term exposure to atmospheric pollutants on the number of acute stroke daily admissions in Taiyuan, China.Methods:The case data of patients with stroke from three large hospitals in different regions of Taiyuan, Shanxi Province from January 1, 2018 to December 31, 2019 were collected. The daily average concentrations of atmospheric pollutants and meteorological data in Taiyuan during the same period were collected. Spearman rank correlation was used to analyze the correlation between meteorological factors and atmospheric pollutants, and a generalized additive model (GAM) based on time series research and analysis was used to investigate the impact and lag effect of air pollutants on the number of stroke daily admissions. Stratified analysis was performed based on different genders and ages (≤64 years, 65-74 years, and ≥75 years).Results:Between 2018 and 2019, a total of 4 921 patients with acute stroke were collected from three large hospitals, with a daily average of 6.74 stroke admissions. Among them, 4 310 patients (87.6%) had ischemic stroke, 521 (10.6%) had cerebral hemorrhage, and 90 (1.8%) had subarachnoid hemorrhage. GAM analysis showed that there was a significant correlation between short-term exposure to PM 2.5, PM 10, and SO 2 and the number of stroke daily admissions. All three had a significant impact on the number of stroke daily admissions on the day of onset and 3 days later. The maximum effect value was reached on the day of onset, and when the average concentrations of PM 2.5, PM 10, and SO 2 increase by 10 μg/m 3, the number of stroke daily admissions increased by 1.48% (95% confidence interval [ CI] 0.46%-2.53%), 0.80% (95% CI 0.25%-1.36%), and 2.80% (95% CI 0.76%-4.88%), respectively. Stratified analysis showed that exposure to PM 2.5, PM 10, SO 2, and CO had a more significant impact on the number of stroke daily admissions in male patients, while only PM 10 showed positive results in females. Age stratified analysis showed that PM 2.5 significantly increased the number of stroke daily admissions in individuals aged ≥75 years. Conclusion:Short-term exposure to atmospheric pollutants (PM 2.5, PM 10, SO 2, and CO) will to some extent increase the number of stroke daily admissions among residents of Taiyuan, especially among males and those aged ≥75 years.

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.

Bacille Calmette-Guérin (BCG) vaccine is designed to provide protection against tuberculosis (TB). However, numerous epidemiological, clinical, and immunological studies have shown that BCG vaccination affects neonatal and infant mortality, which may be related to the reduction of TB-unrelated infections and diseases by BCG vaccine. We aimed to discuss the off-target effects of BCG vaccine on un-TB infections and diseases, as well as the potential mechanism and influencing factors. Literature was retrieved mainly from PubMed using medical subject headings "BCG, variations, and non-specific, heterologous or off-target". Studies have showed that BCG vaccination can prevent various heterologous infections, including respiratory tract infections, leprosy, and malaria, treat viral infections including human papillomavirus and herpes simplex virus infection as immunotherapy, and improve the immune responses as vaccine adjuvant. Besides, BCG vaccine can reduce the recurrence rate of non-muscle-invasive bladder cancer, and may provide protection against autoimmune diseases. These off-target effects of BCG vaccine are thought to be achieved by modulating heterologous lymphocyte responses or inducing trained immunity, which were found to be sex-differentiated and affected by the BCG vaccine strains, sequence or time of vaccination.

Objective:To evaluate the influence of a moisturizer containing oat kernel oil for xeroderma and water content of the stratum corneum in children.Methods:From September to December 2022, 30 children with xeroderma were treated in the Dermatology Department of Tongzhou Maternal and Child Health Hospital of Beijing; 13 were males and 17 were females, and the age was 7.33±2.63 years. This was a single-center self-controlled trial. All children applied the moisturizer on the dry skin of the bilateral limbs two time per day for 14 days, and were followed up at 7 days and 14 days. Efficacy was evaluated according to the water content of the stratum corneum, visual scale, xerosis severity scale (XSS), Specified Symptom Sum Score (SRRC), Visual Analog Scale (VAS) and so on. and side-reactions were recorded.Results:After application of the moisturizer, the median of water content in the stratum corneum was 49.00 (33.83, 87.25), 48.84 (32.58, 100.34) at 7 d and 14 d respectively, showing significant increases compared with that at baseline (median 26.51 (16.00, 47.75) ( Z=-3.075, Z=-2.911, P<0.01). The visual scale, XSS, SRRC and VAS showed that compared with the baseline at 7 d, 14 d, the skin dryness and pruritus scores improved significantly ( Z=-4.424, -4.150, -3.943, -4.400; Z=-4.744, -4.409, -4.260, -4.409, P<0.01). Conclusions:The application of this moisturizer containing oat kernel oil could effectively improve skin dryness and the water content of the stratum corneum without serious adverse reactions.