Hepatocellular carcinoma （HCC） is the sixth most common cancer in the world. In recent years， the clinical early diagnosis and treatment protocols of HCC have been improved， whereas the prognosis of patients is still not satisfactory， which is due to the fact that the mechanism of HCC development has not been fully elucidated. Therefore， it is of great significance to explore the molecular mechanisms and key regulatory links of hepatocellular carcinoma development to further improve the diagnosis and treatment of HCC in China. Epigenetics has become a research hotspot because of its reversibility and easy regulation. According to relevant studies， HCC involves the accumulation of multiple genetic and epigenetic changes during the initiation， promotion， and progression stages. HCC is categorized as infantile malnutrition with accumulation， hypochondriac pain， tympan ites， and abdominal mass in traditional Chinese medicine （TCM）. In the treatment of HCC， TCM with low toxicity， multi-targets， and multi-mechanisms can inhibit tumor growth， alleviate the clinical symptoms， and enhance the quality of life of the patients. Chinese medicines and their active ingredients exert anti-HCC effects through epigenetic regulation of DNA methylation， histone modification， and non-coding RNA. Abnormal gene expression due to epigenetic regulation disorders is involved in all stages of HCC development. There are few studies on epigenetic regulation in TCM treatment of HCC， and there is still much room for development in basic and clinical trials. This paper reviews the mechanism of epigenetic regulation in HCC and summarizes the experimental results of TCM research on the related mechanism， with a view to providing a theoretical basis for future research on the mechanism of HCC development and clinical diagnosis and treatment of hepatocellular carcinoma with TCM.

TROP-2, a tumor-associated antigen, has been implicated in the progression of various epithelial tumors. Due to its favorable expression profile, TROP-2 has emerged as a promising target for antibody-drug conjugates (ADCs) based anti-tumor therapies. Although ADCs have shown efficacy in cancer treatment, their application in solid tumors is hindered by their high molecular weight, poor tumor penetration, and release of cytotoxic molecules. Therefore, a recombinant immunotoxin was developed based on a shark-derived variable domain of immunoglobulin new antigen receptor (VNAR) antibody. VNARs are only one-tenth the size of IgG antibodies and possess remarkable tissue penetration capabilities and high stability. In this study, a shark VNAR phage display library was created, leading to the identification of shark VNAR-5G8 that targets TROP-2. VNAR-5G8 exhibited a high affinity and cellular internalization ability towards cells expressing high levels of TROP-2. Epitope analysis revealed that VNAR-5G8 recognizes a hidden epitope consisting of CRD and TY-1 on TROP-2. Subsequently, VNAR-5G8 was fused with a truncated form of Pseudomonas exotoxin (PE38) to create the recombinant immunotoxin (5G8-PE38), which exhibited significant anti-tumor activity in vitro and in vivo. Overall, this study highlights the promise of 5G8-PE38 as a valuable candidate for cancer therapy.

ObjectiveTo investigate the mediating role of loneliness and social anxiety in the relationship between basic psychological needs satisfaction and smartphone addiction among high school students， and to provide references for the intervention to smartphone addiction for high school students. MethodsIn April 2022， a total of 14 666 high school students from 5 middle schools in a county of Sichuan Province were included by random sampling method. Basic Psychological Needs Scales （BPNS）， the UCLA Loneliness Scale-3 edition （UCLA-3）， Interaction Anxiousness Scale （IAS） and the Mobile Phone Addiction Index （MPAI） were used for cross-sectional investigation. Bootstrap method was used to analyze the mediating role of loneliness and social anxiety in the relationship between the basic psychological needs satisfaction and smartphone addiction. Results① In this study， 14 036 valid questionnaires were returned， and 1 752 （12.48%， 95% CI： 0.114~0.136） high school students were found to be addicted to smartphone phone. The BPNS score was negatively correlated with UCLA-3， IAS and MPAI scores （r=-0.771， -0.486， -0.417， P<0.01）. And MPAI score was positively correlated with IAS and UCLA-3 scores （r=0.403， 0.424， P<0.01）. IAS score was positively correlated with UCLA-3 score （r=0.458， P<0.01）. ②The degree of basic psychological needs satisfaction in high school students can directly negatively predict smartphone addiction （β=-0.383， P<0.05）， and can also indirectly affect smartphone addiction through loneliness and social anxiety （β=-0.130， P<0.05）. ③Loneliness （indirect effect value was -0.145） and social anxiety （indirect effect value was -0.074） partially mediate between the basic psychological needs satisfaction and smartphone addiction. Loneliness-social anxiety also has significant chain mediating effect （indirect effect value was -0.034）， which accounted for 8.88%. ConclusionThe basic psychological needs satisfaction can not only directly affect the occurrence of smartphone addiction， but also indirectly affect the occurrence of smartphone addiction through the chain mediation of loneliness and social anxiety.

Objective: To investigate the epidemiological characteristics of human brucellosis in Jiaxing City from 2010 to 2021, so as to provide insights into the development of the brucellosis control strategy. Methods: The epidemiological and clinical data of brucellosis patients and epidemiological data of brucellosis outbreaks in Jiaxing City from 2010 to 2021 were collected from Chinese Disease Control and Prevention Information System, and the epidemiological features and outbreaks of brucellosis were analyzed descriptively. Results: Totally 160 brucellosis patients were reported in Jiaxing City from 2010 to 2021, and the incidence of brucellosis appeared a tendency towards a rise (χ2trend=28.564, P=0.002), with annual mean incidence of 0.29/105. No deaths due to brucellosis occurred in Jiaxing City from 2010 to 2021. Brucellosis cases were reported each month, which were concentrated in the first and second quarters, and the greatest number was seen in May (27 cases, 16.88%). The brucellosis cases were predominantly reported in Tongxiang City (114 cases, 71.25%), and 75.00% were male (120 cases) and 70.63% were occupational populations (113 cases). The patients had a median (interquartile range) age of 57 (12) years at onset, and the median duration (interquartile range) from onset to definitive diagnosis was 18 (28) days. The clinical manifestations mainly included fever and weakness, and a total of 18 Brucella melitensis isolates and one B. bovis isolate were cultured. Conclusions The incidence of brucellosis was rising in Jiaxing City from 2010 to 2021. The brucellosis patients were predominantly reported in Tongxiang City in the first and second quarters, and young, middle-aged men and occupational populations were at a high risk of brucellosis.

Abstract On March 12, 2022, a case with Plasmodium vivax malaria was reported in the First Hospital of Jiaxing City. The case sought healthcare services due to persist, sharp distending pain of the brain and fever on February 25, 2022, and the symptoms showed no improvements following symptomatic treatment. Microscopy identified malaria parasites on March 12, and the case was definitively diagnosed as P. vivax malaria on March 13. The case was discharged from hospital on March 16 and relapsed on June 15. The case was a veteran from the China-Myanmar border, where malaria is highly prevalent, and had no history of travel after returning to Jiaxing City on October 2021. Based on epidemiological history and laboratory tests, the case was diagnosed as a cross-border mosquito-borne imported case of P. vivax malaria. The case was given treatment with mosquito vector isolation, and the case's family members, neighbors and colleagues were all tested negative for malaria parasites. There was no Anopheles sinensis detected in the case' residence; however, Anopheles was detected in the neighboring areas, indicating a risk of re-establishment. Returners from high-risk regions including borders and labor exporters are recommended to be included in malaria surveillance, and the sensitivity of malaria surveillance requires to be maintained and the diagnostic and treatment capability of malaria requires to be improved in medical institutions.

Objective: To perform an epidemiological survey of the first case with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Pinghu City of Jiaxing City, Zhejiang Province on March 13, 2022, so as to provide insights into the management of coronavirus disease (COVID-19) epidemics. Methods: According to the requirements of the Protocol on Prevention and Control of COVID-19 (8th Edition), epidemiological investigations were performed among 39 cases with SARS-CoV-2 infections in Pinghu City from March 13 to 20, 2022. Cases' demographics, clinical symptoms, history of immunization and exposure were collected, and close contacts were identified. Pharyngeal swabs were sampled from infected cases for detection of SARS-CoV-2 nucleic acid and whole-genome sequencing, and the source of infection and transmission route were investigated. Results: The index case for this COVID-19 epidemic was an imported case from Shanghai Municipality, who infected 6 persons via aerosol transmission when playing in the badminton venue of Pinghu National Fitness Center on March 9; subsequently, one of these infected cases infected another 18 persons when playing in the badminton venue of Jiadian Village Resident's Fitness Center in Zhapu Township on March 12. Sixteen confirmed cases were reported, and all cases were mild; another 23 asymptomatic cases were diagnosed, with no death reported. This epidemic occurred from March 11 to 20, with 3 generations of spread and a median incubation period of 3 days. The SARS-CoV-2 infected cases had a median age of 33.5 (interquartile range, 12.0) years and included 36 cases with a history of COVID-19 vaccination. There were 16 cases with fever, cough, runny nose and sore throat, and 13 cases with imaging features of pneumonia. The effective reproductive number (Rt) of the COVID-19 epidemic was 7.73 at early stage, and was less than 1 since March 21. Whole-genome sequencing identified Omicron BA.2 variant among 33 cases, which had high homology with the index cases. Conclusion This epidemic was a cluster of COVID-19 caused by imported Omicron BA.2 variant infection from Shanghai Municipality, and the COVID-19 transmission was mainly caused by indoor aerosols.

The composition of serum is extremely complex,which complicates the discovery of new pharmaco-dynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and devel-oped a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56％using PC-based proteomic analysis,which was twice the number of proteins iden-tified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

Objective To investigate the feasibility and clinical effect of tranexamic acid in prehospital emergency care of patients with craniocerebral trauma.Methods A randomized,placebo controlled trial was carried out on 77 craniocerebral trauma patients [Glasgow Coma Scale (GCS) ≤12 points]enrolled between May 2015 and December 2016.There were 45 males and 32 females,with an average age of 36.5 years (range,19-73 years).Among the patients,37 cases were caused by traffic accidents,19 falling from high places,11 falling when walking,and ten by being hit.According to the random number table method,they were divided into control group (39 cases) and treatment group (38 cases).The treatment group received 1 g of tranexamic acid by intravenous injection within ten minutes on the scene and another 1 g of tranexamic acid within eight hours at the hospital.The control group received 0.9％ isotonic saline.The operation and medication followed the routine process.The arrival time of ambulance and the time of first medication use were recorded.The plasma fibrin degradation products (FDP) and D-dimer at admission and 1 d post-trauma,the percentage of cranitomy operation,case fatality rate,red blood cell transfusion,length of stay in the neurosurgical intensive care unit (NICU),and the Glasgow Outcome Scale (GOS) at day 28 were all recorded and analyzed.Results No significant differences were found between the two groups in gender,age,injury causes,GCS,arrival time of ambulance,and the time of first medication use (P ＞ 0.05).The FDP and D-dimer at admission of the two groups were similar (P ＞ 0.05).One day after admission,the expression of plasma FDP was significantly lower in treatment group than that in control group [6758 (4732,13661) μg/L vs.11740 (8516,21756) μg/L] (P ＜ 0.01).The expression of D-dimer was significantly lower in treatment group than that in control group [1074 (849,1414) μg/L vs.1722 (1389,2330) μg/L] (P ＜ 0.01).Between group differences were insignificant in the percentage of craniotomy operation,case fatality rate,and red blood cell transfusion (P ＞ 0.05).However,treatment group showed shorter stay in NICU [4 (1,12)days vs.2 (0,4)days] and higher GOS [4 (3,5)points vs.5 (4,5)points]than control group (both P ＜ 0.01).Conclusions Tranexamic acid can be applied conveniently in pre-hospital emergency care of craniocerebral trauma patients.It can effectively realize the synchronization of pre hospital transport and treatment,eventually reducing the time of NICU treatment as well as improving the prognosis.

Objective To investigate the expression of Gli1 protein in colorectal cancer (CRC) tissues,and evaluate its association with the prognoses of the patients.Methods A total of 106 patients were enrolled and their clinicopathological characteristics were analyzed.The expression of Gli1 proteins were detected by immunohistochemical staining,and its association with time to recurrence/metastasis (TTR) and overall survival (OS) of the patients were analyzed.Results The positive rate and expression intensity of Gli1 protein in recurrent or metastatic tumor tissues were higher than those in non-recurrent and non-metastatic tumor tissues [86.84 ％ (33/38) vs.58.82 ％ (40/68),1.32 scores vs.0.71 scores,both P ＜ 0.01),while the positive rate and expression intensity of Ki-67 protein remained no difference between both groups [97.37 ％ (37/38) vs.91.18 ％ (62/68),1.89 scores vs.1.75 scores,both P ＞ 0.05).The positive rates and expression intensities of Gli1 and Ki-67 proteins in CRC tissues were higher than those in adjacent tissues [26.42 ％ (28/106) and 0.27 scores;4.72 ％(5/106),0.05 scores] and normal tissues [3.33 ％ (1/106),0.03 scores;0,0.00 scores] (all P ＜ 0.01).Results of univariate analysis showed that the expression of Gli1 protein,tumor grade and lymph node involvement were significantly associated with TTR,but all of the clinicopathological factors had no obvious association with OS.The association remained significant between the expression of Gli1 protein and TTR in multivariate analysis (P ＜ 0.01).Conclusion The expression of Gli1 protein is an independent prognostic marker of recurrence or metastasis in CRC patients,its high expression implicates a high risk of CRC recurrence or metastasis.

Objective To analyze the characteristics of spontaneous otoacoustic emission in full-term newbo‐rns .Methods The Capella OAE equipment (Madsen ,Denmark) was used to test Spontaneous Otoacoustic Emission (SOAE) in 147 cases (236ears) who have passed the newborn hearing screening with TEOAE(Transient Evoked Otoacoustic Emissions) .Results The SOAE incidence was 56 .77% (male 41 .51% ,female 69 .23% ;left ear 49 .14% ,right ear 64 .17% ) .It was significantly higher in females (P<0 .05) and in right ear (P<0 .05) .The av‐erage amplitude was 11 .78 ± 8 .36 dB SPL( 11 .73 ± 8 .25 dB in male ,11 .81 ± 8 .43 dB SPL in female;11 .97 ± 8 .56 dB SPL in the left ear ,11 .65 ± 8 .22 dB SPL in the right ear) .There were significant differences in genders(P<0 .01) .The frequency of SOAE focused on 3 .2~ 3 .7 kHz(2 .9~3 .4 kHz in males ,3 .4~3 .9 kHz in females ;3 .2~3 .7 kHz in the left ears ,3 .2~3 .6 kHz in the right ears) .There were significant differences in genders(P<0 .01) .The average peak of SOAE was 3 .70 ± 2 .75(3 .86 ± 2 .87 in males ,3 .62 ± 2 .70 in females;3 .70 ± 3 .02 in the left ears ,3 .70 ± 2 .55 in the right ears) .There were no significant differences in genders and laterality .Conclusion The characteristics of SOAE in full-term newborns include higher incidences ,multiple peaks and high frequency distribution .