Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the mod-ulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theo-retically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(p-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electro-phoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while pre-senting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

In this paper， through consulting relevant records in materia medica， medical and prescription books， and combining with modern literature， the name， origin， producing area， collection and processing of Gentianae Macrophyllae Radix in famous classical formulas from The Catalogue of Ancient Famous Classical Formulas （The First Batch） was systematically sorted out and textual research was carried out， in order to provide a basis for the development of the famous classical formulas containing Gentianae macrophyllae Radix. After textual research， it was found that Gentianae Macrophyllae Radix was the rectification of name in the past dynasties. In addition， there were other names such as Qinjiao， Qingua and Qinzhua. Gentiana macrophylla， G. straminea， G. dahurica and G. siphonantha were the main origin of this herb in ancient literature. Among them， G. macrophylla is the mainstream. In the Southern and Northern dynasties， G. straminea and G. macrophylla produced in northern Sichuan were recommended as the best. In the early Tang dynasty， G. macrophylla from the Liupan Mountain area at the border of Shanxi and Gansu provinces was the mainstream. During the Northern Song dynasty， G. siphonantha from Linxia and Qilian Mountain of Gansu province and G. macrophylla from eastern Shaanxi province were two new producing areas. In the Ming and Qing dynasties， the abundant base and production areas of Gentianae Macrophyllae Radix were gradually formed. In the past dynasties， harvesting was carried out in spring and autumn， and stored mainly by aeration drying or shade drying treatment. The processing methods are mainly the raw products after the net selection， cutting and drying， in addition to the frying， processing with wine and milk. G. macrophylla is recommended as the first choice for the herbal medicine involved in the famous classical formulas. Among them， wild products produced in Gansu and Shaanxi are the best， and raw products are recommended to be used. At the same time， it is suggested that G. siphonantha should be added to the subsequent edition of Chinese Pharmacopoeia as one of origins of Gentianae Macrophyllae Radix.

OBJECTIVES: To study the clinical effect of mouse nerve growth factor (mNGF) in the treatment of children with global developmental delay (GDD). METHODS: A prospective clinical trial was conducted in 60 children with GDD who were treated in the First Affiliated Hospital of Anhui Medical University between July 2016 and July 2017. These children were randomly divided into two groups: conventional rehabilitation treatment and mNGF treatment group ( RESULTS: Before treatment and after 1.5 months of treatment, there was no significant difference in the developmental quotient (DQ) of each functional area of the Gesell Developmental Scale between the mNGF treatment and conventional rehabilitation treatment groups ( CONCLUSIONS In children with GDD, routine rehabilitation training combined with mNGF therapy can significantly improve their cognitive, motor, and social abilities.
Animals ; Epilepsy ; Mice ; Prospective Studies ; Social Skills

【Objective】To study the expression of Tip60（KAT5）in Oral squamous cell carcinoma（OSCC），and to investigate the relationship of Tip60（KAT5）and OSCC.【Methods】Forty-nine samples of OSCC and 36 samples of nor⁃ mal tissue adjacent to OSCC were collected and analyzed retrospectively. The expression of Tip60（KAT5）was detected by immunehisto chemistry using Envision detection system. OSCC cell line Cal27 and UM1 cultured in vitro were treated with Nu9056，an inhibitor of Tip60（KAT5）for 24h，respectively. Then the effect of different concentrations and times on the growth of Cal27 and UM1 cells was evaluated with MTT assay.【Results】The expression of Tip60（KAT5）in OSCC was significantly higher than that in normal tissue adjacent to OSCC（P=0.000）. Its expression was significantly positively correlated with the degree of histological differentiation（r=0.461，P=0.001）. With the increase of concentration，the proliferation inhibition rate of Nu9056 on Cal27 and UM1 cells gradually increased，showing a concentration- dependent and time-dependent relationship（P<0.05）.【Conclusions】The expression of Tip60（KAT5）protein in oral squamous cell carcinoma tissues was related to the degree of histological differentiation ，Tip60（KAT5）can be used as oral squamous cell carcinoma progression and prognosis of biological indicators.

Objective The treatment methods for blood blister-like aneurysm remain controversial due to its special patholog-ical structure,the risk of post-operative rebleeding and the high rate of recurrence. The arm of this paper is to access the feasibility and effectiveness of overlapping stent-assisted coiling in the treatment of blood blister-like aneurysms of the internal carotid artery. Methods Form January 2014 to December 2016,we treated 15 patients with blood blister-like aneurysm of the internal carotid artery by stent-assisted coiling in the Department of Neurosurgery,5 with two Enterprise tents,3 with three Enterprise tents,4 with Enter-prise+LVIS tents,and 3 with two LVIS tents. We determined the rate of immediate embolization of aneurysms by Raymond-Roy Occlu-sion Classification(RROC)and analyzed the clinical characteristics,postoperative complications,and follow-up data. Results All the coils and stents were successfully implanted. RROC showed 9 cases of gradeⅠ(60%),4 cases of gradeⅡ(27%),and 2 cases of gradeⅢimmediate occlusion(13%),with the parent arteries unobstructed in all the cases. Thrombosis in the stent was found in 2 cases intraoperatively,slight stent migration in 1 case,and internal carotid artery dissection in the petrous segment in another,but no cer-ebral vasospasm or aneurysm rupture in any case.Delayed cerebral in-farct was observed in 2 cases postoperatively. The patients were fol-lowed up for 2 weeks to 28 months,which showed that 11 of them were cured,2 remained stable and 2 developed further thrombosis,with an MRS score of 0-2 in 12 cases,4 in 1 case,5 in 1 case, and 6 in 1case. Conclusion Overlapping stent-assisted coiling is effective for the treatment of blood blister-like aneurysm by reduc-ing the risks of rebleeding and recurrence.

OBJECTIVESTo analyze the survival outcomes of the surgery for colorectal cancer with liver metastases (CRCLM), and study the mode of multi-disciplinary team (MDT) for CRCLM.

METHODSThe retrospective analysis was conducted for 38 patients with CRCLM received MDT management and surgical treatment from January 2009 to August 2011. The peri-operative and survival outcomes of MDT and surgery were evaluated.

RESULTSAll the cases met the present criteria of resetability for CRCLM, but only 4 cases (10.5%) met the previous one. Coloproctectomy and hepatectomy were performed in all cases, with 39 colorectal neoplasms and 155 liver lesions removed. One case died of postoperative septic shock. Colorectal and hepatic specific complications were absent in the others patients except one case of biliary leak which was treated with conservative management. Neoadjuvant chemotherapy was arranged in 13 cases. Adjuvant chemotherapy was administered for every patient. After a mean follow-up of (22 ± 10) months according to the finding time of liver metastases, recurrence and metastases were observed in 16 cases and 6 cases died of late-stage cachexia. The 1-, 2- and 3-overall survival rate were 94.4%, 85.3% and 75.8% respectively, and the 1-, 2- and 3-disease-free survival rate were 70.1%, 54.2% and 54.2% respectively.

CONCLUSIONSMDT mode for resectable CRCLM is recommendable. Surgical resection of CRCLM is feasible and safe, which seems to achieve favourable short-middle oncologic outcomes. And long-term survival is expected.

Adult ; Aged ; Chemotherapy, Adjuvant ; Colorectal Neoplasms ; mortality ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; mortality ; secondary ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate ; Treatment Outcome

OBJECTIVETo validate those obtained immunogenic membrane antigens candidate of human pancreatic cancer in the performed research.

METHODSIn the pre-studies, serum IgG purified from clinically collected sera of pancreatic cancer patients underwent immunoblot with human pancreatic cancer cell line SW1990 membrane protein, totally obtained 9 positive protein spots. Number 5 and 6 positive dots of immunoblot were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and peptide mass fingerprinting matching. The candidate membrane antigens were further validated in cell lines by RT-PCR and real-time PCR. RNA of human normal pancreatic tissue and pancreatic cancer tissue was extracted respectively, different gene expression level of prohibitin 2 was studied by real-time PCR.

RESULTSNumber 5 and 6 positive dots were identified as prohibitin 2 and prohibitin. RT-PCR and real-time PCR all showed that gene of prohibitin 2 and prohibitin were expressed in the human pancreatic cancer cell line SW1990, AsPc and P3 respectively, especially in P3 cell with highest expression (t = 7.442, P < 0.01). In addition, gene expression level of prohibitin 2 was significant higher in human pancreatic cancer than that of normal pancreatic tissue (t = 0.893, P < 0.01).

CONCLUSIONSProhibitin 2 and prohibitin are both differently expressed in the pancreatic cancer cell line SW1990, AsPc and P3. Prohibitin 2 is obvious highly expressed in human pancreatic cancer tissue. Prohibitin 2 and prohibitin might be the candidate immunogenic membrane antigens of human pancreatic cancer.

Antigens, Neoplasm ; genetics ; metabolism ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Humans ; Membrane Proteins ; genetics ; metabolism ; Pancreatic Neoplasms ; genetics ; immunology ; metabolism ; Proteomics ; methods ; Repressor Proteins ; genetics ; metabolism

Objective To evaluate the effect of health education in controlling the iodine deficiency diserders(IDD) in order to provide reference data for the further prevention and control. Methods Each village of 3 towns in Congjiang County was selected in 2007, where the health education lasting for 10 months had been implemented in the school students of 3-6 grade and the villagers. The school students of 3-6 grade and 30 housewives in the villagers were investigated for their IDD control knowledge, the salt consuming conditions as well as the sales of both rough and fine salt at a salt retail site in each village before and after the health education was implemented. Results The awareness rate of the knowledge of IDD control in the students and housewives was 91.4% (581/636) and 78.3% (282/360), respectively after intervention, which significantly increased (χ2= 532.044, 326.117, both P < 0.01) compared with the rate of 28.2% (184/652) and 11.4% (41/360) before intervention. The proportion of consuming fine salt was 91.8%(146/159) and 95.6%(86/90), significantly inereased(χ2= 236.623, 135.350, both P < 0.01) compared with 6.1%(10/163) and 7.8% (7/90) found before intervention. The selling proportion of fine salt at the salt retail site in the village was 60.0%(900/1500), significantly increased(χ2= 824.176, P < 0.01) compared with 10.0%(150/1500) before intervention. Conclusions Health education and promotion is solid foundation for effectively controlling IDD, through which the students and villagers are actively and voluntarily involved in the program and hence have formed good living and hygiene habits, thus expected effect has been obtained.

OBJECTIVETo better understand the clinical feature of viral gastroenteritis attributed to noroviruses and to summarize the experience on an outbreak of acute gastroenteritis through rapidly colleting and confirmation of related information regarding to noroviruses in hospitals.

METHODSInformation on an outbreaks involving 18 patients with acute gastroenteritis in one hospital regarding its epidemiological and clinical features and to perform bacteria culture for stool specimens on every patient. On 7 patients, rotavirus antigen were RNA tested together with norovirus nucleic acid were examined by ELISA and PAGE and RT-PCR.

RESULTS(1) Most of the patients were elderly with several chronic diseases. (2) Watery diarrhea (12/18, 66.67%) and few with mucous (3/18, 16.67%) were seen. Most stool examination was normal (10/18, 55.56%) but few stool specimen could be found with some leucocytes (3/18, 16.67%) and little occult blood (4/18, 22.22%). (3) All bacteria culture in stools showed negative. There was no rotavirus RNA identified but 3 specimen showed norovirus nucleic acid positive as 42.86% (3/7).

CONCLUSIONNorovirus was one of the important pathogens causing acute gastroenteritis outbreaks in hospitals attacking elderly with several chronic diseases in particular. Surveillance program targeting elderly inpatient with diarrhea should be enhanced, especially in autumn and winter.

Acute Disease ; Aged ; Caliciviridae Infections ; epidemiology ; China ; epidemiology ; Disease Outbreaks ; Enzyme-Linked Immunosorbent Assay ; Feces ; virology ; Gastroenteritis ; epidemiology ; virology ; Hospitals ; statistics & numerical data ; Humans ; Norovirus ; isolation & purification ; Reverse Transcriptase Polymerase Chain Reaction