The androgen receptor plays a suppressive role in epithelial- mesenchymal transition of human prostate cancer stem progenitor cells.

BACKGROUND: To investigate the roles of androgen receptor (AR) in epithelial- mesenchymal transition (EMT) in human prostate cancer stem progenitor (S/P) cells isolated from LNCaP cell line. METHODS: The S/P cells were obtained from LNCaP cell line through florescence-activated cell sorting (FACS). AR was overexpressed in S/P cells through lentivirus. Western blot assay was used to detect the EMT markers expression, such as E Cadherin, N Cadherin, Vimentin and Snail. MTT assay, soft agar colony formation assay, sphere formation assay and migration assay were used to investigate AR's roles in EMT of S/P cells. Cell signaling pathways associated with proliferation and apoptosis of S/P cells were detected simultaneously. And S/P cells were treated with in vitro combinatory use of LY 294002 (inhibitor of AKT signaling molecules) with γ-TT and/or 5-AZA. RESULTS: Our data showed that S/P cells from LNCaP had high EMT markers expression, more tumorigenesis and strong migration ability. And in S/P cells overexpressed with AR, the expression of EMT markers decreased. In addition, these cells had less proliferation ability, tumorigenesis ability, self-renewal and migration ability. At the same time, targeting S/P cells with AKT signaling pathway inhibitor LY29004 and γ-TT and/or 5-AZA could inhibit S/P cell's proliferation and tumorigenesis. CONCLUSIONS: Our data suggest that AR played a negative role in EMT of PCa S/P cells, by regulating AKT cell signaling pathway, which could be a new strategy to treat castration resistant prostate cancer (CRPC).

Amphiplicatus metriothermophilus gen. nov., sp. nov., a thermotolerant alphaproteobacterium isolated from a hot spring.

A thermotolerant, Gram-strain-negative, non-spore-forming and strictly aerobic bacterium, designated GU51(T), was isolated from Guhai hot spring in Jimsar county, Xinjiang province, north-west China. Each cell of strain GU51(T) consisted of an oval body and two symmetrical long (3-6 µm) prosthecae. The strain moved by polar flagellum. Oxidase and catalase were produced. Strain GU51(T) grew within the ranges of 37-65 °C (optimum 48-50 °C), 0.5-7.5% (w/v) NaCl (optimum 2-3%) and pH 6.0-9.0 (optimum pH 7.5). The major respiratory quinone detected was ubiquinone 10 (U-10) and the genomic DNA G+C content was 66.7±0.4 mol%. Major fatty acids (>5%) were C(16 : 0), C(18 : 1)ω7c and 11-methyl C(18 : 1)ω7c. The polar lipids consisted of diphosphatidylglycerol, five glycolipids, phosphatidylglycerol and an unknown phospholipid. Phylogenetic analysis showed the closest relatives of strain GU51(T) were members of the genus Parvularcula with 92.3% 16S rRNA gene sequence similarity. On the basis of this polyphasic taxonomic characterization, it is suggested that strain GU51(T) represents a novel species of a new genus in the family 'Parvularculaceae', for which the name Amphiplicatus metriothermophilus gen. nov., sp. nov. is proposed. The type strain of the type species is GU51(T) ( = CGMCC 1.12710(T) = JCM 19779(T)).

Adsorption performance of GO-doped activated ATP composites towards tetracycline.

Antibiotic-related environmental contamination directly threatens ecosystems and human health. Adsorption is an efficient and simple treatment process for removing antibiotics from water environments. Attapulgite (ATP) is a natural clay mineral extensively researched as a promising adsorbent material in the food industry, pharmaceutical sanitation, and organic wastewater treatment. Graphene oxide (GO) is widely employed in the treatment of organic wastewater due to its superior physicochemical properties. Here, using high temperature and HCl, ATP was activated (a-ATP), and a GO/a-ATP composite was prepared via hydrothermal synthesis. Using an adsorbent dosage of 0.75 g L-1, pH = 5, reaction time of 120 min, initial temperature = 35 °C, and initial TC concentration of 50 mg L-1, the adsorption capacity of GO/a-ATP for TC was 38.8 mg g-1. The pseudo-first-order model (PFO) and pseudo-second-order (PSO) model were fitted to the kinetic data, and yielded an R 2-value of PSO (0.99991) > PFO (0.9389), indicating that the adsorption process is related to chemisorption. Adsorption was also well described by the mixed-order (MO) model (R 2 = 0.9827), demonstrating that two rate-limiting adsorption reaction steps, diffusion and adsorption, occur; the former exerting greater influence. Equilibrium data was fitted to Langmuir, Freundlich, and Temkin isotherm models; the Langmuir model gave the best fit, suggesting the adsorption process is a homogeneous and monolayer adsorption process. Various thermodynamic parameters such as standard Gibbs free energy (ΔG 0) and standard enthalpy (ΔH 0) were also calculated, these results indicate the adsorption reaction is an endothermic process. Our study shows that GO/a-ATP is a promising adsorbent material for use in the adsorption of tetracycline in aquatic environments.

Blood pressure variability related to early outcome of acute ischemia stroke in a prospective observational study.

Hypertension is a well-known risk factor for stroke, but the relationship between blood pressure variation (BPV) and prognosis remains unclear. This prospective observational study assessed the association between BPV and early functional outcomes in acute ischemic stroke patients. A total of 871 patients with acute ischemic stroke within 24 h of symptom onset were recruited from the Third Affiliated Hospital of Qiqihar Medical University between 2013 and 2016. Within 6 days of hospitalization, blood pressure was continuously measured from 8:00 to 9:00 every day, and the coefficient of variation (CV) of blood pressure was calculated (including systolic blood pressure [SBP] and diastolic blood pressure [DBP]). The modified Rankin scale was used to evaluate early functional outcomes at discharge. The coefficients of variation of SBP, DBP, and functional outcomes were included as primary outcome variables. Demographic characteristics and medical history were recorded as secondary outcome variables. We found that a greater CV level of SBP and DBP were associated with the poor early functional outcome at hospital discharge, and the odds ratio (OR) and 95% confidence interval (95%CI) of them were 1.56 (1.04-2.35) and 1.99 (1.31-3.03) respectively. A higher standard deviation (SD) of SBP and DBP significantly increased risk of poor early prognosis, OR (95%CI) was 1.78 (1.17-2.71) and 2.25 (1.47-3.45) respectively. Similar results were observed for SBP and DBP. The larger the range of SBP and DBP, the worse is the prognosis. In conclusion, the present study suggests that high BPV is a risk factor for poor early prognosis in acute ischemic stroke.

Interaction of TPPP3 with VDAC1 Promotes Endothelial Injury through Activation of Reactive Oxygen Species.

Endothelial injury plays a critical role in the pathogenesis of cardiovascular disorders and metabolic-associated vascular complications which are the leading cause of death worldwide. However, the mechanism underlying endothelial dysfunction is not completely understood. The study is aimed at investigating the role of tubulin polymerization-promoting protein family member 3 (TPPP3) in palmitic acid- (PA-) induced endothelial injury. The effect of TPPP3 on human umbilical vein endothelial cells (HUVECs) was determined by evaluating apoptosis, tube formation, and reactive oxygen species (ROS) production. TPPP3 silencing inhibited PA overload-induced apoptosis and production of ROS, along with the alteration of apoptosis-related key proteins such as BCL-2 and Bax. Mechanically, voltage-dependent anion channel 1 (VDAC1) was identified as a novel functional binding partner of TPPP3, and TPPP3 promoted VDAC1 protein stability and its activity. Further studies indicated that TPPP3 could promote apoptosis, ROS production, tube formation, and proapoptotic protein expression and reduce antiapoptotic protein expression through increasing VDAC1 expression under mildly elevated levels of PA. Collectively, these results demonstrated that TPPP3 could promote PA-induced oxidative damage in HUVECs via a VDAC1-dependent pathway, suggesting that TPPP3 might be considered as a potential therapeutic target in vascular disease.

Application of a novel nanoemulsion adjuvant for rabies vaccine which stabilizes a Krebs cycle intermediate (SDH) in an animal model.

Rabies is the most lethal zoonotic, vaccine-preventable viral disease in the world. Its treatment is complicated by insufficient vaccine supply and the requirement for four to five repeated injections, as commercially available inactivated rabies lack adjuvant and have low immunogenicity. In this study, we focused on the role of a Krebs cycle intermediate, succinate dehydrogenase (SDH), in the innate immune response to cytokine production. We formulated a novel nanoemulsion adjuvant, Golden03, which stabilizes mouse SDH activity and contains more coenzyme Q10 and succinic acid than the classic MF59 adjuvant. Mice were immunized on days 1, 3, and 7, with seroconversion rate results suggesting that Golden03 significantly enhanced vaccine-stimulated antibody production against the rabies virus. Neutralizing antibody concentration testing by RFFIT indicated that treatment with Golden03 could result in antibody levels of up to 0.74 IU/mL 5 days post infection (DPI). ELISPOT for IFN-γ in mouse spleen cells showed that Golden03 enhanced immune responses at 14 DPI, inducing a rapid and powerful cellular response compared to the control group. Furthermore, the Vaccine-Golden03 group displayed no obvious weight loss or death after intracranial injection with CVS-11. An additional advantage is that Golden03 allowed for a three-quarter reduction in dose, while maintaining its efficacy and rapid stimulation effect. We suggest that Golden03 could be developed as a potential adjuvant for use in human rabies vaccine.

Discussion on the Discipline Structure of Chinese Medical Humanities Based on the Views of Chinese Scholars / 中国医学伦理学

Discipline structure, as the core of discipline construction, plays an important role in promoting the prosperity of medical humanities. By sorting out the Chinese scholars’ division of the structure of medical humanities in China, this paper preliminarily discussed the existence of the subordinate discipline of medical humanities in China, and preliminarily verified the rationality and feasibility the viewpoint of "building a first-class discipline of medical humanities under the medical category, and forming a subordinate discipline of medical humanities based on horizontal association". At the same time, this paper put forward the view that the structure of medical humanities in China should be determined according to the needs of the current social development in China, and the concepts and criteria contained in the division of the Chinese discipline catalogue, so as to pave the way for the follow-up research.

Advances in Research Methods of Tumor Angiogenesis / 肿瘤防治研究

Nowadays, angiogenesis has gradually become one of the most popular research directions of cancer since Jodah Folkman put forward a theory about that tumor development needs angiogenesis. Meanwhile, relevant research methods are enriched step by step. In this paper, we have made a systematic review to provide methodological references for subsequent studies about tumor angiogenesis and antiangiogenic therapy.

The predictive value of renal artery resistance index combined with cystatin C in contrast-induced nephropathy after coronary artery CT angiography / 中国医师进修杂志

Objective:To investigate the predictive value of serum cystatin C (Cys-C) and renal artery resistance index (RRI) 24 h before coronary CT angiography (CTA) examination in contrast-induced nephropathy(CIN).Methods:Sixty-four patients with coronary heart disease who received coronary CTA examination in Hebei Petro China Central Hospital from January 2020 to March 2021 were selected as the research subjects. According to the incidence of CIN after coronary CTA examination, they were divided into the case group (25 patients) and the normal group(39 patients). Serum Cys-C level was measured by automatic biochemical analyzer at 24 h before CTA examination, and RRI value was measured by color Doppler ultrasound. Risk factors of CIN after CTA examination were analyzed by Logistic regression. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of serum Cys-C, RRI and the combination of the two indexes in CIN.Results:Compared with the control group, the dosage of contrast agent, patients with hypertension, serum Cys-C level at 24 h before CTA examination and RRI value in the case group were higher than those in the normal group: (85.53 ± 16.27) ml vs. (64.37 ± 15.08) ml, 80.00%(20/25) vs. 56.41%(22/39), (1.36 ± 0.18)mg/L vs.(1.02 ± 0.21) mg/L, 0.743 ± 0.093 vs. 0.632 ± 0.081, there were statistical differences ( P<0.05). Multivariate Logistic regression analysis showed that the amount of contrast agent, hypertension, serum Cys-C level at 24 h before CTA examination and RRI value were independent risk factor for CIN after CTA examination ( P<0.05). The results of ROC curve analysis showed that serum Cys-C (>1.318 mg/L) combined with RRI value (>0.653) at 24 h before CTA examination predicted CIN with the highest area under the curve was 0.922, sensitivity was 92.5% and specificity was 81.6%. Conclusions:The incidence of CIN after CTA is related to the dosage of contrastant, hypertension, serum Cys-C level and RRI value at 24 h before CTA. The combination of Cys-C level and RRI value has a high predictive value for the occurrence of CIN.

Analysis of the re-entry status of voluntary blood donors with single reagent reactivity in Hohhot / 中国输血杂志

【Objective】 To statistically analyze the re-entry test and blood re-donation of HBV, HCV, TP and HIV single-reagent reactive blood donors in Hohhot from 2019 to 2021, so as to demonstrate the rationality, feasibility and necessity of the re-entry strategy of voluntary blood donors in Hohhot, and provide theoretical support for further standardizing of the reentry of blood donors. 【Methods】 A total of 225 samples of blood donors who applied for re-entry in Hohhot from 2019 to 2021 were collected, and HBV, HCV and HIV were tested by two reagent serological tests and nucleic acid tests. TP anti-TP was detected by two reagent serological methods. The test results were all non-reactive and met the requirements of re-entry. The blood donation status of blood donors after re-entry was followed up and analyzed. 【Results】 Among the 225 cases detected for HBV, HCV, TP and HIV from 2019 to 2021 in Hohhot, 178 were qualified for the returning, with a re-entry rate of 79.11%, and 75 donated blood again, with a after re-entry re-donation rate of 42.13%. 【Conclusion】 The strategy of returning for HBV, HCV, TP and HIV single reagent reactive blood donors in Hohhot is effective, and has positive significance for safeguarding the rights and interests of blood donors and alleviating regional blood supply shortages.

Progress in Clinical Diagnosis and Management of Hypermobility Spectrum Disorders / 罕见病研究

@#Joint hypermobility (JH) refers to the ability of joints to move beyond the 'normal' limits, which can be either physiologic or pathologic. Hypermobility spectrum disorders (HSDs) are a group of joint hypermobility-related clinical conditions. HSDs primarily affects the musculoskeletal system, predisposing the joints to subluxations or dislocations, and chronic pain. HSDs, however, may also manifest with symptoms such as fatigue, gastrointestinal disorders, and autonomic nervous system dysfunction, indicating multisystemic involvement that may impact psychological well-being. Although HSDs is usually not life-threatening, it is associated with poor quality of life. Currently, the molecular basis of HSDs remains unclear. The diagnosis of HSDs requires comprehensive medical evaluation and assessment. The main differential conditions/diagnoses include asymptomatic joint hypermobility, hypermobile Ehlers-Danlos syndrome (hEDS), and various musculoskeletal inflammatory or degenerative diseases. Asymptomatic joint hypermobility, HSDs, and hEDS are now viewed as a continuous spectrum. Due to limited awareness of the condition, individuals with asymptomatic joint hypermobility may experience overdiagnosis and overtreatment, while patients with HSDs may encounter prolonged misdiagnoses or underdiagnoses. Furthermore, individuals presenting with psychological symptoms may have all their somatic complaints erroneously attributed to psychological factors. These factors collectively impose unnecessary psychological and economic burdens on patients and their families. The multi-systemic and heterogeneous nature of HSDs necessitates a multi-disciplinary team (MDT) approach with a case manager in both the diagnosis and management processes. Additionally, patient education and self-management play pivotal roles in optimizing chronic disease management. This review aims to summarize the current state of diagnosis and management of HSDs and raise awareness of HSDs, providing a basis for the establishment and refinement of a multi-disciplinary diagnostic and management framework for HSDs in China.

A Case Report of Gorham-Stout Syndrome with Kyphoscoliosis / 罕见病研究

This article reported the treatment of Gorham Stout syndrome (GSS) with kyphoscoliosis. The patient was an 11-year-old male who was presented with kyphoscoliosis, first developed 4 years ago, accompanied by incomplete paralysis of both lower limbs. The syndrome worsened in the previous year. He had a history of chylothorax, ventilation dysfunction, and osteoporosis. The patient underwent skull traction in another hospital for 7 months, which was ineffective. Finally, he underwent posterior correction, internal fixation, and bone graft fusion (C4-T8) in our hospital. The postoperative clinical outcomes and the posterior correction were satisfactory, with significant improvement in incomplete paralysis of both lower limbs. This article aims to improve the understanding of GSS and provided reference for its diagnosis and treatment through a typical case report and review of previous literature.

Progress in the Research of the Spinal Deformity Related to Marfan Syndrome / 罕见病研究

Marfan syndrome(MFS) is an autosomal dominant systemic connective tissue disease. The incidence rate of MFS is about 2-3 per 10 000. Main cause of MFS is FBN1 gene mutation. About 2/3 of MFS patients have spinal deformities, showing symptoms of scoliosis, thoracic lordosis and lumbar kyphosis, severe spondylolisthesis, dural dilatation and pedicle dystrophy. MFS scoliosis develops with age and may continue even after bone maturation. Conservative treatments such as brace are usually ineffective. Surgical treatment of main curve > 40°-45 °is recommended, but due to the special anatomical structure of MFS patients, such surgical complications as dural leakage, failure of internal fixation and revision surgery are not uncommon.

The Role of Deep Phenotyping of Precision Medicine for Rare Bone Diseases / 罕见病研究

Deep phenotyping is a precise and comprehensive approach used for the precise analysis and comprehensive assessment of multi-system phenotypes of the patients. The approach uses symptoms, signs, various medical examination and laboratory results, and other relevant medical information. In the clinical diagnosis and medical research of rare bone diseases, deep phenotyping plays a pivotal role. The realization of precision medicine primarily comprises three key dimensions: deep phenotyping, stratified medicine, and targeted therapy. The deep phenotyping is the basis for the latter two. Deep phenotyping not only facilitates fine subtyping of diseases, but also allows for the in-depth understanding of genetic data. The use of deep phenotyping requires stand- ardized terminology and specific procedures. Moreover, deep phenotyping shows substantial potential using the application of artificial intelligence technology particularly when combining with multi-omics techniques.

Identification and analysis of terpene synthase (TPS) gene family in Schizonepeta tenuifolia / 中国中药杂志

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.

Study on processing and enhance the curative effects of Arisaematis rhizomz preparatum based on network pharmacology / 中国药理学通报

Aim To explore the mechanism of process¬ing and increasing efficiency of Arisaematis rhizomz preparatum. Methods UPLC-Q-TOF-MS/MS tech¬nology was used to detect the chemical components be¬fore and after processing of Arisaematis rhizomz prepara¬tum, and its mechanism of action was analysed in the treatment of 44 asthma and phlegm " by using network pharmacology. A rat model of allergic asthma was es- tablished to compare the efficacy of Arisaematis rliizoma before and after processing. Results A total of 27 chemical components were identified, among which cur- cumin ,6-gingerol and other components increased after processing. Combined with the database prediction, the action mechanism of the 36 chemical components in the treatment of 44 asthma and phlegm" diseases was dis¬cussed and predicted through network pharmacology. The results of animal experiments showed that the effect of processed Arisaematis rhizoma on allergic asth¬ma was better than that of Arisaematis rhizoma, but there was no significant difference. Conclusions The addition of curcumin, 6-gingerol, camphor, demethyl- curcumin and other components after the processed Ari¬saematis rhizomz preparatum may be the reason for the synergistic effect of Arisaematis rhizomz preparatum in the treatment of allergic asthma.

Percutaneous foraminal endoscopy for the treatment of lumbar lateral recess stenosis in elderly / 中国骨伤

OBJECTIVE@#To investigate the clinical efficacy and safety of percutaneous foraminal endoscopy in the treatment of lumbar lateral recess stenosis in elderly.@*METHODS@#The clinical data of 31 elderly patients with lumbar lateral recess stenosis treated by percutaneous foraminal endoscopic decompression from March 2018 to August 2019 were retrospectively analyzed. Including 16 males and 15 females, aged from 65 to 81 years with an average of (71.13±5.20) years, the course of disease ranged from 3 months to 7 years with an average of (14.36±6.52) months. Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to assess clinical symptom and functional status before operation and 1, 6, 12 months after operation. At the final follow-up, the modified Macnab standard was used to evaluate clinical efficacy.@*RESULTS@#All patients were completed the operation successfully. The operation time was from 75 to 120 min with an average of (97.84±11.22 ) min. All 31 patients were followed up from 12 to 28 months with an average of (17.29±5.56) months. Postoperative lumbago-leg pain VAS and ODI were significantly improved at 1, 6, and 12 months(P<0.01). At the final follow-up, according to the modified Macnab standard to evaluate the effect, 23 got excellent results, 5 good, 3 fair. One patient had severe adhesions between peripheral tissues and nerve root, and postoperative sensory abnormalities in the lower extremities were treated conservatively with traditional Chinese medicine and neurotrophic drugs, which recovered at 2 weeks after surgery. No complications such as nerve root injury and infection occurred.@*CONCLUSION@#The intervertebral foraminal endoscopy technique, which is performed under local anesthesia for a short period of operation, ensures adequate decompression while minimizing complications, and is a safe and effective surgical procedure for elderly patients with lumbar lateral recess stenosis.

Pathological evaluation of 30 cases of esophageal squamous cell carcinoma after two neoadjuvant therapies / 中华放射肿瘤学杂志

Objective:To explore the pathological differences of surgically resected specimens of advanced esophageal squamous cell carcinoma (ESCC) to different neoadjuvant therapies (neoadjuvant radiochemotherapy and toripalimab combined with neoadjuvant radiochemotherapy).Methods:Thirty patients diagnosed with advanced ESCC who underwent surgical operation after neoadjuvant therapy in Jiangsu Cancer Hospital from October 2020 to September 2021 were included. Among them, 15 patients received neoadjuvant radiochemotherapy (radiochemotherapy group) and 15 patients were treated with toripalimab combined with radiochemotherapy (immunotherapy combined with radiochemotherapy group). Surgically resected specimens were collected. The histopathological features of primary esophageal lesions and the responses of involved lymph nodes were analyzed and compared between two groups.Results:The major pathological response (MPR) rate in the radiochemotherapy group was 10/15, and 14/15 in the immunotherapy combined with radiochemotherapy group ( P=0.17). The pathological complete response (pCR) rate of the primary lesions in the radiochemotherapy group was 7/15, and 10/15 in the immunotherapy combined with radiochemotherapy group ( P=0.46). In the radiochemotherapy group, the incidence rate of tertiary lymphoid structure (TLS) was 7/15, and 12/15 in the immunotherapy combined with radiochemotherapy group ( P=0.02). The incidence rate of necrosis in the radiochemotherapy group was 6/15, and 1/15 in the immunotherapy combined with radiochemotherapy group ( P=0.03). In addition, the incidence rate of foam cell infiltration in the radiochemotherapy group was 6/15, and 13/15 in the immunotherapy combined with radiochemotherapy group ( P=0.01). Furthermore, the pCR rate of involved lymph nodes in the radiochemotherapy group was 7/33, and 11/12 in the immunotherapy combined with radiochemotherapy group ( P<0.001). Conclusion:Compared with the radiochemotherapy group, the incidence of TLS and foam cell infiltration is higher, the incidence of necrosis is lower and clinical efficacy of involved lymph nodes is higher in the immunotherapy combined with radiochemotherapy group, prompting that toripalimab combined with neoadjuvant radiochemotherapy exert higher synergistic immune effect.

Clinicopathological and molecular features of metaplastic thymoma / 中华病理学杂志

Objective: To investigate the clinicopathological features, and molecular genetic alterations of metaplastic thymoma (MT). Methods: A total of ten MT cases, diagnosed from 2011 to 2021, were selected from the Department of Pathology of Jinling Hospital, Nanjing University Medical School, Nanjing, China for clinicopathological and immunohistochemical (IHC) examination and clinical follow-up. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and YAP1 C-terminus (YAP1-CT) IHC were performed to detect YAP1::MAML2 fusions. Results: There were four males and six females, ranging in age from 29 to 60 years (mean 50 years, median 54 years). Microscopically, all tumors showed a typical biphasic morphology consisting of epithelial components and gradually or abruptly transitioning spindle cell components. The two components were present in varying proportions in different cases. Immunophenotypically, the epithelial cells were diffusely positive for CKpan, CK5/6 and p63. The spindle cells were diffusely positive for vimentin and focally positive for EMA. TdT was negative in the background lymphocytes. Ki-67 proliferation index was less than 5%. YAP1 and MAML2 break-apart FISH analyses showed that all ten cases had narrow split signals with a distance of nearly 2 signal diameters and may be considered false-negative. Using YAP1::MAML2 fusion FISH assays, abnormal fusion signals were observed in all the ten cases. NGS demonstrated YAP1::MAML2 fusions in all eight cases with adequate nucleic acids; in two cases the fusions were detected by DNA sequencing and in eight cases by RNA sequencing. All ten cases of MT demonstrated loss of YAP1 C-terminal expression in epithelioid cells. Conclusions: MT is a rare and low-grade thymic tumor characterized by a biphasic pattern and YAP1::MAML2 fusions. Break-apart FISH assays may sometimes show false-negative results due to the proximity of YAP1 and MAML2, while YAP1 C-terminal IHC is a highly sensitive and specific marker for MT. Loss of YAP1 C-terminal expression can also be used to screen YAP1::MAML2 fusions for possible MT cases.

Quality evaluation of Lysimachiae Herba from different habitats based on simultaneous determination of multiple bioactive constituents combined with multivariate statistical analysis / 中国中药杂志

A method based on ultra-high performance liquid chromatography coupled with triple quadrupole linear ion trap-tandem mass spectrometry(UHPLC-QTRAP-MS/MS) was developed for the simultaneous determination of 41 bioactive constituents of flavonoids, organic acids, nucleosides, and amino acids in Lysimachiae Herba. The content of multiple bioactive constituents was compared among the samples from different habitats. The chromatographic separation was performed in a Waters XBridge®C_(18) column(4.6 mm×100 mm, 3.5 μm) at 30 ℃. The gradient elution was performed with 0.4% methanol(A)-formic acid water(B) as the mobile phase at a flow rate of 0.8 mL·min~(-1), and the multiple-reaction monitoring(MRM) mode was adopted. According to the content of 41 constituents, hierarchical cluster analysis(HCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and gray relational analysis(GRA) were perfomed to comprehensively evaluate the samples from different habitats. The results showed that the 41 constituents exhibited good linear relationship within the tested concentration ranges, with the correlation coefficients(r) greater than 0.999 4. The method featured good precision, repeatability, and stability with the relative standard deviations(RSDs) less than 5.0%. The average recoveries of the 41 constituents ranged from 98.06% to 101.9%, with the RSDs of 0.62%-4.6%. HCA and OPLS-DA separated 48 batches of Lysimachiae Herba samples from different habitats into three categories: the producing areas in Sichuan and Chongqing, the producing areas in Jiangsu, Zhejiang, and Jiangxi, and the producing areas in Guizhou. The content of 41 constituents varied among the Lysimachiae Herba samples from different habitats. The GRA results revealed that the Lysimachiae Herba sample from Nanchong City, Sichuan Province had the best comprehensive quality. The method developed in this study was accurate and reliable and thus can be used for comprehensive evaluation of Lysimachiae Herba quality and provide basic information for the selection of habitats.