Refractory prolactinoma is the most common pituitary neuroendocrine tumor.Dopamine receptor agonists(DA)are the primary choice for drug treatment.Most patients with prolactinomas respond well to DA.However,a minority of prolactinomas patients still show resistance to DA.Although drug-resistant and refractory prolactinomas are rare in clinical practice,their treatment is extremely challenging.Even a combination of drug therapy,multiple surgeries,and radiotherapy may not yield satisfactory outcomes.Therefore,standardizing the diagnosis and treatment process and pathway for refractory prolactionmas and exploring more effective multidisciplinary collaborative treatment strategies are urgent problems to be solved.In the clinical management of refractory prolactinomas,it is often necessary to consider the patient's condition comprehensively,replace other types of DA,or consider surgery,radiotherapy,and immunotherapy,which requires multidisciplinary diagnosis and treatment.This review synthesizes the latest literature at home and abroad to systematically discuss the latest advances in drug therapy,surgery,and radiotherapy treatments for refractory prolactionmas,aiming to provide new ideas for basic research,clinical diagnosis and treatment.

In the research on cancer theranostics, most environment-sensitive drug delivery systems can only achieve unidirectional and irreversible responsive changes under pathological conditions, thereby improving the targeting effect and drug release performance of the delivery system. However, such irreversible changes pose potential safety hazards when the dynamically distributed delivery system returns to the blood circulation or transports to the normal physiological environment. Intelligent reversible drug delivery systems can respond to normal physiological and pathological microenvironments to achieve bidirectional and reversible structural changes. This feature will help to precisely control the drug release of the delivery system, prolong the blood circulation time, improve the targeting efficiency, and avoid the potential safety hazards of the irreversible drug delivery system. In this review, we describe the research progress of intelligent reversible drug delivery system from two main aspects: controlled drug release and prolonged blood circulation time/enhanced cellular internalization of drug.

This study aims to explore the molecular regulation mechanism of the differential accumulation of flavonoids in the leaves and roots of Sarcandra glabra. Liquid chromatography-mass spectrometry(LC-MS) and high-throughput transcriptome sequencing(RNA-seq) were employed to screen out the flavonoid-related differential metabolites and differentially expressed genes(DEGs) encoding key metabolic enzymes. Eight DEGs were randomly selected for qRT-PCR verification. The results showed that a total of 37 flavonoid-related differential metabolites between the leaves and roots of S. glabra were obtained, including pinocembrin, phlorizin, na-ringenin, kaempferol, leucocyanidin, and 5-O-caffeoylshikimic acid. The transcriptome analysis predicted 36 DEGs associated with flavonoids in the leaves and roots of S. glabra, including 2 genes in the PAL pathway, 3 genes in the 4CL pathway, 2 genes in the CHS pathway, 4 genes in the CHI pathway, 2 genes in the FLS pathway, 1 gene in the DFR pathway, 1 gene in the CYP73A pathway, 1 gene in the CYP75B1 pathway, 3 genes in the PGT1 pathway, 6 genes in the HCT pathway, 2 genes in the C3'H pathway, 1 gene in the CCOAOMT pathway, 1 gene in the ANR pathway, 1 gene in the LAR pathway, 2 genes in the 3AT pathway, 1 gene in the BZ1 pathway, 2 genes in the IFTM7 pathway, and 1 gene in the CYP81E9 pathway. Six transcription factors, including C2H2, bHLH, and bZIP, were involved in regulating the differential accumulation of flavonoids in the leaves and roots of S. glabra. The qRT-PCR results showed that the up-or down-regulated expression of the 8 randomly selected enzyme genes involved in flavonoid synthesis in the leaves and roots of S. glabra was consistent with the transcriptome sequencing results. This study preliminarily analyzed the transcriptional regulation mechanism of differential accumulation of flavonoids in the leaves and roots of S. glabra, laying a foundation for further elucidating the regulatory effects of key enzyme genes and corresponding transcription factors on the accumulation of flavonoids in S. glabra.
Metabolome ; Gene Expression Regulation, Plant ; Flavonoids ; Gene Expression Profiling ; Transcriptome ; Transcription Factors/metabolism*

Terpenoids are important secondary metabolites of plants that possess both pharmacological activity and economic value. Terpene synthases(TPSs) are key enzymes in the synthesis process of terpenoids. In order to investigate the TPS gene family members and their potential functions in Schizonepeta tenuifolia, this study conducted a systematic analysis of the TPS gene family of S. tenuifolia based on the whole genome data of S. tenuifolia using bioinformatics methods. The results revealed 57 StTPS members identified from the genome database of S. tenuifolia. The StTPS family members encoded 285-819 amino acids, with protein molecular weights ranging from 32.75 to 94.11 kDa, all of which were hydrophilic proteins. The StTPS family members were mainly distributed in the cytoplasm and chloroplasts, exhibiting a random and uneven physical localization pattern. Phylogenetic analysis showed that the StTPS genes family were divided into six subgroups, mainly belonging to the TPS-a and TPS-b subfamilies. Promoter analysis predicted that the TPS gene family members could respond to various stressors such as light, abscisic acid, and methyl jasmonate(MeJA). Transcriptome data analysis revealed that most of the TPS genes were expressed in the roots of S. tenuifolia, and qRT-PCR analysis was conducted on genes with high expression in leaves and low expression in roots. Through the analysis of the TPS gene family of S. tenuifolia, this study identified StTPS5, StTPS18, StTPS32, and StTPS45 as potential genes involved in sesquiterpene synthesis of S. tenuifolia. StTPS45 was cloned for the construction of an prokaryotic expression vector, providing a reference for further investigation of the function and role of the TPS gene family in sesquiterpene synthesis.
Phylogeny ; Terpenes/metabolism* ; Plant Proteins/metabolism* ; Lamiaceae/genetics* ; Sesquiterpenes

Abstract: Objective Methods Toevaluatetheriskofhearinglosscausedbyworkplacenoiseinurbanrailtransitenterprises. Noiseexposedworkers from eight rail transit lines in an urban rail transit enterprise was selected as the research subjects - usingconvenientsamplingmethod.Thenoiseintensitywasdetected,andtheriskofnoise inducedhearinglosswaspredictedby Results the method of the International Organization for Standardization. The incidence of noise exceeded the standard detection points was 8.3% (175/2 101) from 2016 to 2018. For risk classification in interval tunnel repairmen, higher risk was predictedattheageof40yearsoldandwiththelengthofserviceof20years,andhighriskwaspredictedattheageof50or60 yearsoldwiththelengthofserviceof30or40years.Theriskclassificationofstationinspectoratthepredictedageof 50years oldandthepredictedageof30yearswasnegligible,anditwasacceptableatthepredictedageof60yearsoldandthepredicted ageof40years.TheriskgradesofmaintenanceworkersinvehicledepotundertheabovetwopredictedconditionsweremediumConclusionrisk,whiletheriskclassificationofdriversunderwasacceptablerisk.Therailtransitenterprisehasacertain degreeofnoisehazardsintheoperationprocess.Theriskanddegreeofhearinglosscausedbynoiseincreaseswiththeincrease ofthelengthofservice.

Objective To analyze the epidemiological characteristics of hepatitis A in Guangxi from 2010 to 2020, and to provide a scientific basis for formulating effective prevention and control strategies. Methods Descriptive epidemiological method was used to analyze the incidence data of hepatitis A in Guangxi from 2010 to 2020. Results From 2010 to 2020, a total of 8,742 cases of hepatitis A were reported in Guangxi, with an average annual incidence rate of 1.66 /100,000. There were 5 298 male cases (60.60%), and 3,444 female cases (39.40%). The incidence rate decreased from 2.73/100 000 in 2010 to 1.38/100 000 in 2020. The onset seasonality was strong in 2010, but there was no obvious seasonality in other years. A total of 5 891 cases (67.39%) were aged from 25 to 64 years. Farmers accounted for 59.79% of the cases. A total of 7 hepatitis A outbreaks were reported during 2010-2020, including 273 cases，accounting for 3.12% of the total cases．The incidence rates of hepatitis A in Hezhou (3.97/100 000), Wuzhou (2.98/100 000), Hechi (2.44/100 000), Guigang (2.00/100 000) and Beihai (1.79/100 000) were relatively higher than other places. Conclusion The number of reported hepatitis A cases in Guangxi has been declining year by year, and the prevention and control measures of hepatitis A vaccine prevention are effective. The surveillance of hepatitis A should be strengthened, and prevention and control strategies should be formulated for high-risk areas and key populations.

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

Objective: To know the pre-treatment drug resistance ( PDR ) status of newly reported human immunodeficiency virus type 1 ( HIV-1 ) infected individuals in Wenzhou, so as to provide guidance for antiretroviral therapy ( ART ). Methods: Totally 232 plasma samples of newly reported HIV-1 infected individuals who had not received ART were collected in Wenzhou in 2019. Virus ( HIV-1 ) RNA was extracted, followed by reverse transcription PCR and nested PCR to amplify the pol region and sequence. Resistance mutations and resistance to non-nucleoside reverse transcriptase inhibitors ( NNRTIs ), nucleoside reverse transcriptase inhibitors ( NRTIs ) and protease inhibitors ( PIs ) was analyzed. Results: The pol region sequences from 199 infected patients were obtained and the incidence of PDR was 8.04% ( 16/199 ). Eight genotypes were detected, including circulating recombinant forms ( CRFs ) CRF07_BC ( 47.24%, 94/199 ) and CRF01_AE ( 29.15%, 58/199 ) which were the dominant types. Two unique recombinant forms ( URFs ) were detected, namely URF( CRF01_AE/BC ) and URF( B/C ) . Thirty-one cases ( 15.58% 31/199 ) had drug-resistant mutations. For NNRTIs, NRTIs and PIs, 20 cases ( 64.52% ) , 2 cases ( 6.45% ) and 9 cases ( 29.03% ) with drug resistance mutations were detected, respectively. The resistance mutations to NNRTIs included K101E, K103N/R, V106I, E138K, V179D/E/T, Y181C, G190A and H221Y. Four cases each had two resistance mutations to NNRTIs. The resistance mutations to NRTIs were V75M and M184V. The resistance mutations to PIs were M46I, L33F and Q58E. For the newly released NNRTI drug Doravirine ( DOR ), two cases were found to have mutations of resistance. Conclusions The incidence of PDR among newly reported HIV-1 patients in Wenzhou is 8.04%, mainly caused by NNRTIs drug-resistant mutation. Resistance to the new drug DOR has emerged. The surveillance of drug resistance should continue to be strengthened.

To investigate the effects of exogenous NaHS on myelin basic protein (MBP) and learning and memory of hippocampal neurons in mice with spinocerebellar ataxia type 3 (SCA3) and its therapeutic significance. Twelve male normal mice were randomly selected as normal control group (NC Group), and 48 SCA3 mice were randomly selected as SCA3 model group (M Group), low dose group (NL Group, 10 μmol/kg), medium dose group (NM Group, 50μmol/kg) and high dose group (NH Group, 100 μmol/kg), 12 rats in each group. The drug treated groups were injected with NaHS intraperitoneally once a day for 4 weeks. The changes of learning and memory ability of SCA3 mice before and after the intervention of different doses of NaHS were determined by Morris water maze, the content of hydrogen sulfide (HS) in hippocampus was measured by spectrophotometry, the expression of MBP was detected by immunohistochemistry, and the morphological changes of neuron myelin sheath were observed by electron microscope. Compared with the control group, the learning and memory ability of SCA3 mice was decreased significantly (P＜0.05), and the content of HS in hippocampus was decreased (P＜0.05). After different doses of exogenous NaHS treatment, the learning and memory ability was improved in different degrees (P＜0.05), and the contents of HS and MBP in hippocampus of SCA3 mice were also improved in different degrees (P＜0.05). Exogenous NaHS may increase the contents of HS and MBP in the hippocampus of SCA3 mice, which may have a protective effect on the neurons, and then improve the learning and memory ability of SCA3 mice, and provide a new idea for the treatment of SCA3.

Objective:To study the mechanism of Tiaogeng decoction in improving apoptosis of hypothalamic neurons through c-Jun N-terminal kinase (JNK) pathway. Method:The GT1-7 cell line of hypothalamic neuron cells treated by tributyltin chloride (TBTC) was used to induce a model of neuronal apoptosis, with 17β-estradiol as a positive drug. They were divided into control group, model group (1 mg·L^-1), 17β-E₂ group(100 nmol·L^-1) and low, middle and high-dose Tiaogeng decoction groups (31.25,62.5,125 mg·L^-1). The cell morphology was observed under a fluorescent inverted microscope, and cell counting kit-8 (CCK-8) was used to detect the cell viability. The cell nuclear morphology and the apoptosis rate of hypothalamic neurons were detected by Hoechst 33258 and Annexin V-FITC/propidium iodide(PI) double staining. Western blot was used to detect the expression levels of apoptosis signal-regulating kinase 1(ASK1), JNK, p53 and cleaved Caspase-3 of JNK pathway in GT1-7 cell. Western blot was used to analyze apoptosis-associated protein apoptosis signal-regulated kinase 1 (ASK1), JNK, p53, cleaved Caspase-3 expressions in JNK pathway and phosphorylation of JNK after intervention with JNK inhibitor SP600125, protein expression level of cleaved Caspase-3. Result:Compared with normal control group, the cell viability of the model group was significantly decreased (P<0.01), whereas the apoptotic rate was significantly increased (P<0.01). The expressions of phosphorylated ASK1(p-ASK1), p-JNK, phosphorylated p53 (p-p53) and cleaved Caspase-3 increased significantly (P<0.01). After intervention with Tiaogeng decoction, compared with model group, the activity of GT1-7 cells was significantly improved(P<0.01), while the apoptotic rate was decreased (P<0.01). The expressions of p-ASK1, p-JNK, p-p53, and cleaved Caspase-3 proteins were down-regulated. High-dose Tiaogeng decoction combined with SP600125(10 μmol·L^-1)treatment significantly inhibited the expressions of p-JNK and cleaved Caspase-3 in GT1-7 cells (P<0.01). Conclusion:Tiaogeng decoction can improve the apoptosis of hypothalamic neurons through JNK pathway, and provide a theoretical basis for the treatment of menopausal syndrome and central nervous system protection.