177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Aim To evaluate the therapeutic effect of apigenin on liver fibrosis in mice anrl the pharmacologi¬cal mechanism.Methods Carbon tetrachloride ( CC14) -induced liver fibrosis mouse model was estab¬lished.The mice were divided into six groups of con¬trol, model, silibinin(55 mg • kg 1 • d 1 ) , apigenin in high dosage (60 mg • kg 1 • d 1 ) , apigenin in mid¬dle dosage( 30 mg • kg 1 • d 1 ) and apigenin in low dosage( 15 mg • kg 1 • d 1 ).The general life status, body weight and liver coefficient of the mice in every group were recorded.HE staining, Masson staining, immunohistochemistry and Western blot were used to e- valuate the effect of apigenin on the pathological chan¬ges, the markers related to epithelial-mesenchymal transition and signaling pathways of liver tissues.Re¬sults In CCI4-induced liver fibrosis mice, middle and high-dosage of apigenin could improve the general life status, increase body weight, decrease liver coeffi¬ cient, and significantly improve liver lesions.Middle and high-dosage of apigenin significantly increased the expression of the epithelial marker protein E-cadherin and significantly decreased the expression of the mes¬enchymal marker protein Vimentin in liver tissues of mice with the disease.The further results showed that middle and high-dosage apigenin could significantly in¬hibit the expression of phosphorvlated PDK1 and phos- phorvlated AKT protein in liver tissues of model mice.Conclusions Apigenin can inhibit EMT by inhibiting PDK1/AKT signaling pathway, which plays an anti-fi- brosis role.The apigenin has the potential to be further developed as a drug to protect the liver and treat liver fibrosis.

Objective:To understand the epidemiological and clinical characteristics of melioidosis in Haikou City, to rise the people's awareness of melioidosis and to provide basis for prevention and control of the disease.Methods:The clinical data of 254 patients with melioidosis treated in 4 Class A tertiary hospitals in Haikou City from January 2000 to September 2020 were collected, and the epidemiological characteristics, clinical manifestations, infection site, prognosis and drug sensitivity were retrospectively analyzed.Results:Among 254 patients with melioidosis, 226 males (88.98%) and 28 females (11.02%), and the gender ratio was 8.07 ∶ 1.00. Farmers were the main occupation, accounting for 37.80% (96/254). The median age was 53 years old, mainly in 41 - 80 years old, accounting for 83.46% (212/254). Han nationality was the most, accounting for 89.76% (228/254). The onset season was mainly in summer and autumn, and the peak was from August to October (117 cases). Patients were mainly distributed in coastal areas, among which Haikou City (49 cases) was the most, followed by Dongfang City (46 cases), Danzhou City (23 cases) and Wenchang City (21 cases). Totally 196 cases (77.17%) had basic diseases, diabetes was the most common (162 cases). The main symptoms of admission were fever (211 cases), followed by cough (108 cases) and expectoration (88 cases). The infection sites were mainly blood (104 cases, 40.94%), lung (60 cases, 23.62%), liver and spleen (32 cases, 12.60%). Totally 195 patients were treated with sensitive antibiotics, at discharge, 37 cases (18.97%) were cured, 129 cases (66.15%) improved, 18 cases (9.23%) did not heal, 7 cases (3.59%) died and 4 cases (2.05%) were discharged voluntarily. Results of drug sensitivity tests from 2010 to 2020 showed that the sensitivity rates of Burkholderia pseudomallei to imipenem (142 cases), meropenem (16 cases) and ceftazidime (141 cases) were all 100.00%, and the sensitivity rates of doxycycline (25 cases) and compound sulfamethoxazole (142 cases) were 92.00% (23/25) and 99.30% (141/142), respectively. Conclusions:Males, farmers, middle-aged and elderly people and people with diabetes and other basic diseases are the high incidence population of melioidosis in Haikou City. The incidence peak is in summer and autumn. The common clinical manifestations are fever, pulmonary infection, abscess of liver and spleen, etc. In the treatment, Burkholderia pseudomallei is more sensitive to imipenem, meropenem and ceftazidime.

This paper aimed to explore the mechanism of the split components of Phytolaccae Radix by means of network pharmaco-logy. Based on the theoretical hypothesis of the nature and taste of traditional Chinese medicine, the chemical components of the separated components of Phytolaccae Radix were selected by using Traditional Chinese Medicine Systems Pharmacology Database(TCMSP) and Traditional Chinese Medicines IntegratedDatabase(TCMID) databases in combination with related literatures. Relevant target analysis was carried out based on PubChem and SwissTargetPrediction databases. Targets corresponding to disease were excavated based on GeneCards for each split component, corresponding potential targets were obtained through mapping the target set of target compounds to disease targets. GO biological process analysis and KEGG pathway enrichment analysis were performed on the mapped targets with the help of DAVID database. Based on Cytoscape software and the corresponding efficacy, the network diagram of "medicinal material-split components-compound-target-pathway" was constructed to explore the mechanism of different efficacy of the separated components of Cytoscape. And the target purgation and diuretic mapping was used as the target of the traditional efficacy of smoothening secretion for the first time. The study explored esculentoside component, fatty oil component and phenolic acid component, a total of 30 target compounds and 301 corresponding targets, involving 44 potential targets for "anti-inflammatory", 50 potential targets for "immunoregulation", 52 potential targets for "smoothening secretion", 28 potential targets for "antibacterial activity", 28 potential targets for "antiviral effect", and 29 potential targets for "antitumor effect". Topological analysis revealed 14 key gene targets such as MAPK8, MAPK14, EGFR and PTGS2. A total of 684 GO entries and 235 KEGG pathways were obtained through bioinformatics enrichment analysis, mainly involving TNF signaling pathway, NF-kappaB signaling pathway and MAPK signaling pathway. This study revealed the multi-component, multi-target, and multi-channel action mechanism of the split components of Phytolaccae Radix, which provided certain basis for the next step to clarify the split components of Phytolaccae Radix through the method of system biology, and injected new content and significance into the study of properties and flavors theory.
Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional ; Signal Transduction ; Software

【Objective】To provide a rabbit model for dry eye using a dry environment induced by Controlled Drying System.【Methods】Twenty-four male New Zealand rabbits were used in the experiment. They were randomly divided into control group and dry group，each one with 12 rabbits. The dry group was randomly housed in Controlled Drying System（CDS）for 14 days. The relative humidity，airflow and temperature were kept at（22±4）%，3~4 m/s and（23~25）℃， respectively. The control group were fed in a normal environment where relative humidity，airflow and temperature were kept at 60%~70%，0.2 m/s and（23~25）℃. The Schirmer test，corneal fluorescein staining，conjunctival lissamine green staining were performed during the experimental process on days 0，3，7，and 14. On the last day，the rabbits were euthanized and the eye tissues were made into paraffin-cut sections. After staining，we evaluated the corneal epithelial thickness and goblet cell number in the conjunctiva using light microscopy. MUC5AC in the conjunctival epithelium was detected by immunofluorescence. The apoptosis level changes on the ocular surface were evaluated using Caspase- 3 by immunohistochemistry. 【Results】 Decreased tear production ，increased corneal fluorescein staining and increased conjunctival lissamine green staining were found on days 3，7，and 14 in the dry group compared with the control group（P < 0.001）. Corneal epithelial thickness of control group and dry group were （58.0±7.2）μ m and（47.8±7.6）μ m ，which showed corneal epithelial thickness of dry group was decreased（P＜0.05）. Goblet cells in the conjunctiva of control group and dry group were 15 ± 4 and 10 ± 2，which showed goblet cells of dry group was decreased（P＜0.01）. The expression of MUC5AC（consistent with goblet cells deficiency） was also reduced. Caspase- 3 was highly expressed on the corneal epithelium in the dry group. IOD/field of control group and dry group were（17±2）% and（20±2）%（P＜0.01）.【Conclusions】 Dry environment can make rabbits have pathological changes of dry eye on ocular surface epithelium. This dry eye model of rabbit caused by Controlled Drying System would be an effective tool to study the pathogenesis of dry eye.

Herpes simplex virus type 1 (HSV-1) is a ubiquitous and widespread human pathogen, which gives rise to a range of diseases, including cold sores, corneal blindness, and encephalitis. Currently, the use of nucleoside analogs, such as acyclovir and penciclovir, in treating HSV-1 infection often presents limitation due to their side effects and low efficacy for drug-resistance strains. Therefore, new anti-herpetic drugs and strategies should be urgently developed. Here, we reported that baicalein, a naturally derived compound widely used in Asian countries, strongly inhibited HSV-1 replication in several models. Baicalein was effective against the replication of both HSV-1/F and HSV-1/Blue (an acyclovir-resistant strain)

Next generation sequencing (NGS) has developed very rapidly in the last decade. Compared with Sanger sequencing, NGS has the advantages of high sensitivity and high throughput. Movement disorders are a common type of neurological disease. Although traditional linkage analysis has become a standard method to identify the pathogenic genes in diseases, it is getting difficult to find new pathogenic genes in rare Mendelian disorders, such as movement disorders, due to a lack of appropriate families with high penetrance or enough affected individuals. Thus, NGS is an ideal approach to identify the causal alleles for inherited disorders. NGS is used to identify genes in several diseases and new mutant sites in Mendelian movement disorders. This article reviewed the recent progress in NGS and the use of NGS in Mendelian movement disorders from genome sequencing and transcriptome sequencing. A perspective on how NGS could be employed in rare Mendelian disorders is also provided.
Alleles ; Genetic Linkage ; High-Throughput Nucleotide Sequencing ; methods ; Humans ; Movement Disorders ; diagnosis ; genetics ; Sequence Analysis, DNA ; Transcriptome

Objective To observe the change of serum leptin in different risk stratifications of coronary heart disease (CHD) and to investigate its relationship with the severity of coronary artery lesion and the coronary artery Gensini score and its value in the coronary heart disease risk stratification .Methods According to coronary angiography ,120 research subjects were enrolled and di-vided into 4 groups :the non-CHD group ,stable angina(SAP) group ,unstable angina pectoris(UAP) group and myocardial infarc-tion group(AMI) ,respectively .The serum leptin levels in 4 groups were determined by immunoassay and the correlation between the leptin level with the coronary heart disease risk factor and biochemical markers of risk assessment was analyzed .Results The serum leptin level in the AMI group was significantly higher than that in the non-CHD group and the SAP group ,the leptin level showed the increasing trend with the increase of the coronary lesion severity and the Gensini scores and was positively related with the CHD risk stratification indicators cTnT and smoking index ,and negatively related with blood uric acid .Conclusion The serum leptin may be used as the valuable marker for evaluating the occurrence of acute coronary event and has good correlation with usual biochemical markers of CHD risk stratification and the severity of coronary artery lesion .

Liver cancer is a common malignant tumor in China and a major health concern. We aimed to estimate the liver cancer incidence and mortality in China in 2010 using liver cancer data from some Chinese cancer registries and provide reference for liver cancer prevention and treatment. We collected and evaluated the incidence and mortality data of liver cancer in 2010 from 145 cancer registries, which were included in the 2013 Chinese Cancer Registry Annual Report, calculated crude, standardized, and truncated incidences and mortalities, and estimated new liver cancer cases and deaths from liver cancer throughout China and in different regions in 2010 from Chinese practical population. The estimates of new liver cancer cases and deaths were 358,840 and 312,432, respectively, in China in 2010. The crude incidence, age-standardized rate by Chinese standard population (ASR China), and age-standardized rate by world standard population (ASR world) were 27.29/100,000, 21.35/100,000, and 20.87/100,000, respectively; the crude, ASR China, and ASR world mortalities were 23.76/100,000, 18.43/100,000, and 18.04/100,000, respectively. The incidence and mortality were the highest in western regions, higher in rural areas than in urban areas, and higher in males than in females. The age-specific incidence and mortality of liver cancer showed a rapid increase from age 30 and peaked at age 80-84 or 85+. Our results indicated that the 2010 incidence and mortality of liver cancer in China, especially in undeveloped rural areas and western regions, were among high levels worldwide. The strategy for liver cancer prevention and treatment should be strengthened.
China ; epidemiology ; Female ; Humans ; Incidence ; Liver Neoplasms ; epidemiology ; mortality ; Male ; Registries ; Rural Population ; Sex Distribution ; Urban Population

BACKGROUNDUrotensin II (UII) is a new vasoconstrictive peptide that may activate the adventitial fibroblasts. Transforming growth factor-β1 (TGF-β1) is an important factor that could induce the phenotypical transdifferentiation of adventitial fibroblasts. This study aimed to explore whether TGF-β1 is involved in UII-induced phenotypic differentiation of adventitial fibroblasts from rat aorta.

METHODSAdventitial fibroblasts were prepared by the explant culture method. TGF-β1 protein secretion from the cells was determined by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expression of α-smooth nuscle actin (α-SM-actin), the marker of phenotypic differentiation from fibroblasts to myofibroblasts, were determined using real-time quantitative RT-PCR (real-time RT-PCR) and Western blotting, respectively.

RESULTSUII stimulated the secretion of TGF-β1 in cultured adventitial fibroblasts in a time-dependent manner. The secretion reached a peak at 24 hours, was higher by 69.8% (P < 0.01), than the control group. This effect was also concentration dependent. Maximal stimulation was reached at 10(-8) mol/L of UII (P < 0.01), which was increased by 59.9%, compared with in the control group (P < 0.01). The secretion of TGF-β1 induced by UII was significantly blocked by SB-710411 (10(-7) mol/L), a specific antagonist of UII receptor. In addition, both UII (10(-8) mol/L) and TGF-β1 significantly stimulated α-SM-actin mRNA and protein expression. Moreover, the α-SM-actin induced by UII was inhibited by the specific neutralizing antibody (20 µg/ml) of TGF-β1, while the α-SM-actin expression stimulated by TGF-β1 (20 ng/ml) was inhibited by SB-710411 (10(-7) mol/L), the UII receptor antagonist.

CONCLUSIONThis study suggests that UII could induce TGF-β1 secretion in adventitial fibroblasts via UT activation, and TGF-β1 might be involved in phenotypic differentiation from adventitial fibroblasts into myofibroblasts induced by UII, and TGF-β1 signaling might be one of the important pathways by which UII is involved in vascular fibrosis.

Actins ; analysis ; genetics ; Animals ; Aorta ; cytology ; Cell Transdifferentiation ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Fibroblasts ; cytology ; drug effects ; Male ; Myofibroblasts ; cytology ; Phenotype ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Signal Transduction ; Transforming Growth Factor beta1 ; physiology ; Urotensins ; antagonists & inhibitors ; pharmacology