Gentianopsis barbata (G. barbata) represents a significant plant species with considerable ornamental and medicinal value in China. This investigation sought to elucidate the primary constituents within the plant and investigate their pharmacological properties. Fifty triterpenoids (1-50), including nine previously undescribed compounds (1, 2, 7, 10, 20, 28, 29, 37, and 41) were isolated and characterized from the whole plants of G. barbata. Notably, compounds 1 and 2 exhibited the novel 3,4;9,10-diseco-24-homo-cycloartane triterpenoid skeleton. The isolated triterpenoids demonstrated substantial anti-inflammatory activity through inhibition of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) cytokine secretion in LPS-induced RAW264.7 macrophages, and hepatoprotective effects by preventing tert-butyl hydroperoxide (t-BHP)-induced oxidative injury in HepG2 cells. These results demonstrate both the presence of diverse triterpenoids in G. barbata and their therapeutic potential for inflammatory and hepatic conditions, providing scientific evidence supporting the clinical application of this traditional Mongolian medicinal plant.
Triterpenes/isolation & purification* ; Mice ; Anti-Inflammatory Agents/isolation & purification* ; Animals ; Humans ; RAW 264.7 Cells ; Hep G2 Cells ; Interleukin-6/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Medicine, Mongolian Traditional ; Macrophages/immunology* ; Protective Agents/isolation & purification* ; Liver/drug effects* ; Gentianaceae/chemistry* ; Plant Extracts/chemistry* ; Molecular Structure

Objective:To analyze the gene mutation type and clinical phenotype of patients with PRRT2 mutation, and explore their relations with prognosis. Methods:A total of 18 patients with PRRT2 gene mutation (1 patient with novel mutation in PRRT2 gene, and 17 probands in 17 families with PRRT2 gene mutation) were enrolled in Department of Neurology, First Affiliated Hospital of Air Force Medical University from January 2018 to July 2023. Serum of the patients was collected for whole exon sequencing, and mutation sites and types of PRRT2 gene were analyzed. SWISS-MODEL website was used to predict the changes in protein structure caused by PRRT2 gene mutation. The relations of gene mutation type and clinical phenotype with prognosis of these patients were analyzed. Results:(1) All 18 patients with PRRT2 gene mutation were heterozygous mutation, including 12 frameshift mutations, 5 missense mutations, and 1 integer mutation. The clinical phenotype included benign familial infantile epilepsy (BFIE) in 5 patients, epilepsy in 6 patients, exercise-induced paroxysmal kinesigenic dyskinesia (PKD) in 5 patients, and infantile convulsion and choreoathetosis (ICCA) in 2 patients. A total of 8 mutation sites were found in 18 patients with PRRT2 gene mutation, of which 3 mutation sites have been reported, and 5 mutation sites have not been reported, including c.647(exon2)C>A, c.647(exon2)C>G, c.170(exon2)delC, c.981(exon3)C>G, and lossl(EXON: 2)(all). (2) Eighteen patients mainly accepted oxcarbazepine, levetiracetam, and sodium valproate in combination or monotherapy. Among them, 5 BFIE patients, 2 ICCA patients and 3 epilepsy patients were seizure-free after treatment. PKD patients did not respond well to oxcarbazepine. (3) Three frameshift mutations (mutation sites: c.649 [exon2]_c.650 [exon2] insC, c.640 [exon2]_c.641 [exon2] insC, and c.170 [exon2] delC) led to premature termination of protein translation, resulting in significant changes in protein structure. Four missense mutations (mutation sites: c.640[exo2]G>C, c.647[exon2]C>A, c.647[exon2]C>G, and c.981[exon3]C>G) had little effect on protein structure changes. No relation was found between changes of protein structure caused by different mutation types and prognosis. Conclusion:PRRT2 gene mutation patients with clinical phenotypes of BFIE and ICCA have good prognosis, but the mutation type is not related with the prognosis of patients.

Objective:To explore the differences in clinicopathological features, survival status and prognostic influencing factors of breast cancer patients with different molecular subtypes, and to provide bases for the prevention and treatment of breast cancer.Methods:The clinicopathological data of new-onset female breast cancer patients hospitalized in Shanxi Province Cancer Hospital from January 2015 to December 2016 were retrospectively analyzed, and patients were followed up. The clinicopathological features of patients with different molecular subtypes were compared. The follow-up was performed until June 30, 2021. Kaplan-Meier method was used to analyze the survival of patients, and Cox proportional hazards model was used to analyze the factors affecting overall survival (OS) of patients with different molecular subtypes.Results:There were 272 (14.9%), 1 005 (55.2%), 277 (15.2%) and 268 (14.7%) patients with subtypes of Luminal A, Luminal B, human epidermal growth factor receptor 2 (HER2) overexpression and triple-negative breast cancer (TNBC), respectively. The differences in the distribution of patients with age at diagnosis, age at menarche, menopausal status, age at menopause, pathological type, longest tumor diameter, T staging, N staging, histological grading, and TNM staging were statistically significant among the four groups (all P < 0.05). At a median follow-up of 60 months, the 5-year OS rates of Luminal A, Luminal B, HER2 overexpression and TNBC subtypes were 93.8%, 89.2%, 77.6% and 78.0%, respectively, and the difference was statistically significant ( χ2 = 58.76, P < 0.001). M staging was an independent influencing factor for OS in patients with Luminal A breast cancer ( HR = 16.789, 95% CI 4.972-56.690, P < 0.001); T staging ( HR = 2.721, 95% CI 1.715-4.319), N staging ( HR = 4.460, 95% CI 2.399-8.291) and M staging ( HR = 3.364, 95% CI 1.988-6.670) were independent influencing factors for OS in patients with Luminal B breast cancer (all P < 0.001); N staging ( HR = 4.428, 95% CI 1.836-10.677) and M staging ( HR = 13.489, 95% CI 6.043-30.107) were independent influencing factors for OS of patients with HER2 overexpression breast cancer (both P < 0.01); T staging ( HR = 3.052, 95% CI 1.575-5.915), N staging ( HR = 2.492, 95% CI 1.298-4.785) and M staging ( HR = 33.012, 95% CI 8.606-126.637) were independent influencing factors for OS of patients with TNBC (all P < 0.01). Conclusions:The clinicopathological features and prognostic influencing factors of breast cancer patients with different molecular subtypes are different, and the prognosis of HER2 overexpression and TNBC patients is poor. Clinicians should provide individualized treatment and follow-up programs for patients with different molecular subtypes of breast cancer.

Objective:To report the clinical phenotype and mutation site of a patient with grey matter heterotopia caused by a de novo heterozygous missense mutation in the TUBB2B gene, and to expand the phenotypic and mutational spectrum of TUBB2B mutations. Methods:One patient with TUBB2B mutation who presented to the Department of Neurology, the First Affiliated Hospital of Air Force Medical University in July 2017 was collected and analyzed for clinical features and mutation site, and a review of previous studies was performed. Results:The male patient started at the age of 18 and presented mainly with seizures, poor left-handed fine motor skills and poor spatial imagination. Magnetic resonance imaging showed nodular grey matter heterotopia in the right cerebral hemisphere, right frontoparietal-temporal localized cerebral gyrus, and cerebral sulcus shallow flat.The whole exon gene test suggested a heterozygous missense mutation in the TUBB2B gene: c.776 C>T (p.Pro259Leu), which was wild-type in both of his parents. The mutation site was located between the tubulin and tubulin-c structural domains and did not affect the function of the essential structural domain. After treatment with magnesium valproate in combination with levetiracetam, the patient′s seizure symptoms were significantly controlled and he has been seizure-free for 3 years now. Conclusions:The TUBB2B gene c.776 C>T (p.Pro259Leu) heterozygous missense mutation is a novel missense mutation causing grey matter heterotopia. The patient had a good prognosis, and the combination of two antiepileptic drugs resulted in complete seizure control.

Objective:To explore the clinicopathological characteristics and factors influencing the survival of young breast cancer patients with diagnostic age below 35 years, and to provide the basis for the prevention and treatment of young breast cancer patients.Methods:Epidemiological and clinicopathological data of young female patients with newly diagnosed breast cancer from Shanxi Province Cancer Hospital between January 2015 and December 2016 were retrospectively analyzed. The data included age at diagnosis, reproductive history, history of abortion, menopausal status, and immunohistochemical results. Univariate and multivariate analysis were performed by using Cox regression model.Results:A total of 118 young breast cancer patients were collected, and the median age was 31 years old. Among them, the vast majority of 118 young breast cancer patients were invasive cancer (113 cases, accounting for 95.8%); there were 65 cases (55.1%) with tumor diameter ≤ 20 mm, 61 cases (51.7%) at N 0 stage, and 112 cases (94.9%) at M 0 stage. The positive rates of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) were 73.7% (87/118), 69.5% (82/118) and 28.8% (34/118), respectively. Luminal B breast cancer was the predominant molecular subtype, accounting for 55.1% (65/118). By the end of follow-up (median follow-up period of 60 months), the overall survival rate of young breast cancer patients was 78.8%. Multivariate analysis showed that TNM staging was an independent factor affecting overall survival in young breast cancer patients ( HR = 7.858, 95% CI 2.924-21.120, P < 0.001). Conclusions:Young breast cancer patients have unique clinicopathological features and TNM staging is an independent factor affecting the prognosis. Individualized treatment helps to improve the quality of life and prolong the survival time of patients.

Objective:To investigate the association between breast cancer and thyroid diseases, and to provide evidence for the prevention and treatment of thyroid diseases in breast cancer patients.Methods:A total of 511 newly diagnosed breast cancer patients were recruited between March 2018 and August 2019 from Shanxi Province Cancer Hospital, and 303 age-matched newly diagnosed breast benign disease patients and 341 age-matched healthy controls were recruited during the same time-frame. Thyroid B-ultrasound and thyroid function test were performed in the three groups. By reviewing the medical records, the general and clinicopathological data of the patients were collected, and the differences in the prevalence of thyroid diseases among the three groups were compared. The changes of thyroid function in breast cancer patients before treatment, in the middle stage of chemotherapy and at the end of chemotherapy were compared.Results:Among breast cancer group, breast benign disease group and healthy control group, the differences in the prevalence rates of hypothyroidism [32.5% (166/511), 25.7% (78/303) and 21.7% (74/341)], thyroid nodules [50.7% (259/511), 43.2% (131/303) and 41.6% (142/341)] and Thyroid Imaging Reports and Data System(TI-RADS) grade 4 and above thyroid nodules [15.4% (40/259), 14.5% (19/131) and 4.9% (7/142)] were statistically significant (all P < 0.05). The abnormal rates of thyroid stimulating hormone (TSH) and free thyroxine (fT4) in breast cancer group were higher than those in breast benign disease group and healthy control group [34.1% (174/511) vs. 26.1% (79/303), 23.5% (80/341); 24.9% (127/511) vs. 8.6% (26/303), 3.2% (11/341)], and the differences were statistically significant (both P < 0.05). The levels of fT4, free three iodide thyroxine (fT3), thyroid immunoglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) in breast cancer patients before treatment, in the middle stage of chemotherapy and at the end of chemotherapy were statistically different (all P < 0.05). The abnormal rates of fT4, TgAb and TPOAb in the last chemotherapy cycle were lower than those before chemotherapy [11.5% (59/511) vs. 24.9% (127/511), 5.1% (26/511) vs. 17.4% (89/511), 11.9% (61/511) vs. 20.4% (104/511)] in breast cancer patients, and the differences were statistically significant (all P < 0.001). Conclusions:The breast cancer is associated with thyroid diseases. Clinicians should pay more attention to the changes of thyroid diseases and thyroid function during the treatment and in the follow-up process of breast cancer patients, so as to detect the thyroid diseases early and carry out standardized treatment.

Cholangiocarcinoma is a malignant tumor of the biliary tract with high heterogeneity and poor prognosis. Surgery is the only cure for early cholangiocarcinoma, but about two thirds of the patients are already advanced at the time of initial diagnosis. First-line chemotherapy in patients with advanced cholangiocarcinoma does not lead to viable survival. In recent years, with the development of second-generation sequencing technology, potential targets in cholangiocarcinoma have been continuously discovered, and a series of clinical trials have been carried out accordingly. Among them, clinical trials of drugs targeting fibroblast growth factor receptors (FGFRs) have yielded promising results. This article reviews the current status and research progress of drugs targeting FGFRs in the treatment of advanced cholangiocarcinoma.

A survey on professional knowledge levels was conducted from April to October 2019 among 388 general practitioners (GPs) from 46 community health service centers and 30 township health centers of 6 provinces selected by stratified random sampling method. The overall knowledge test score was 31.82—84.09(56.94±9.19) points, and the pass rate was 36.3% (141/388). There were significant differences in test scores among participants with different types of work units, regions, provinces, marital status, educational background, professional titles, types of employment, length of service, and training status (all P<0.05). Multivariate regression analysis showed that educational background ( B=-2.835), professional title ( B=-8.867), and participation in professional course training ( B=2.214) were the influencing factors of knowledge level (all P<0.05). The pass rates in knowledge of prevention/health management (13.7%, 53/388) and policies and regulations (12.1%, 47/388) were low. The results show that the levels of professional knowledge among GPs working in grassroots health institutions are relatively low, and suggest that continuing education should be strengthened to improve the professional knowledge level of GPs in primary care institutions, particularly, knowledge of health policies and regulations, disease prevention and health management.

Objective:To observe the safety of intravitreal injection of triamcinolone acetonide (TA) combined with partial anterior pars plana vitrectomy (PPV) for cataract with severe vitreous hemorrhage.Methods:A retrospective case-control study. A total of 60 patients (60 eyes) with cataract and severe vitreous hemorrhage were included from June 2017 to June 2019 in Xi’an People’s Hospital (Xi’an Fourth Hospital). There were 32 males (32 eyes) and 28 females (28 eyes), with a mean age of 64.8 years. The eyes were randomly divided into intravitreal injection TA group (TA group) and non-TA injection group (control group), with 30 eyes in each group. Before phacoemulsification, 0.05-0.10 ml TA was injected into the vitreous cavity in the TA group and the vitreous besides the vitrectomy channel was removed. The eyes of the control group underwent conventional cataract phacoemulsification combined with PPV. The follow-up time after surgery was ≥6 months. The rate of success continuous circular capsulorhexis, posterior capsule rupture, and intraocular lens (IOL) implantation in the capsular bag were compared between the two groups. The statistical data were compared with χ2 test. Results:For all eyes in the TA group, after intravitreal injection of TA combined with partial anterior PPV, the white reflection of the fundus can clearly show the anterior and posterior capsule of the lens. Continuous circular capsulorhexis was completed, the posterior capsule was not broken, and the IOL was successfully implanted inside the capsular bag. Among the 30 eyes of the control group, 4 eyes did not complete continuous circular capsulorhexis. Radial tear occurred during capsulorhexis, and capsulorhexis was used to complete capsulorhexis. In 5 eyes with posterior capsule rupture, the posterior capsule occurred in 3 eyes during phacoemulsification, and injecting the lens cortex caused posterior capsule repture in 2 eyes; the IOL was implanted in the ciliary sulcus and the capsular bag in 4 and 1 eyes, respectively. Whether the consecutive capsulorhexis was successful ( χ2=4.286), whether the posterior capsule was ruptured ( χ2=5.455), whether the IOL was implanted in the capsular bag ( χ2=4.286), the differences in the number of eyes between the two groups were statistically significant ( P= 0.038, 0.020, 0.038). At the last follow-up, no special complications occurred. Conclusions:Intravitreal injection of TA combined with partial anterior PPV can improve the visibility of the anterior and posterior lens capsule and lens nucleus during phacoemulsification in patients with cataract and severe vitreous hemorrhage. The surgical success rate is high, the complications are few, and the safety is good.

Objective: The aim of the study was to investigate association of response depth and prognosis in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC)patients treated with first-line tyrosine kinase inhibitors (TKIs). Methods: The clinicopathological data and prognosis information of patients with locally advanced or metastatic (ⅢB or Ⅳ) lung adenocarcinoma with EGFR classical (19del or 21L858R) mutation who were treated in our hospital from 2015 to 2016 were collected. The tumor remission depth [stable disease (SD), partial response (PR), complete response (CR)] was measured by recist 1.1 standard. The survival curve was drawn by Kaplan-Meier method and log rank test was performed. Results: During the study period, 204 advanced lung adenocarcinoma patients with 19del or 21L858R mutation were treated with TKI drugs of the first generation. Among them, 24 patients were lost or unable to evaluate the efficacy, 20 patients were evaluated as progression disease (PD), 62 patients as SD, 98 patients as CR or PR. Disease control rate (DCR) and objective remission rate (ORR) were 88.9% and 54.4%, respectively. The median progression free survival time (PFS) was 12.6 months (95% CI: 10.9-14.4 months) and 13.1 months (95% CI: 11.6-14.7) for patients assessed as SD (group A) and CR or PR (group B), respectively, with no significant difference (P=0.27). Subgroup analysis showed that the median overall survival of patients with EGFR 19del and 21L858R mutations was 12.5 months (95% CI: 9.9-15.4) and 12.7 months (95% CI: 9.4-16.1), respectively, with no significant difference (P=0.66); Similar result was also observed in Group B with a median PFS of 13.9 months (95% CI: 12.3-15.5 months) and 12.3 months (95% CI: 9.5-15.1 months) in patients who had EGFR 19del or 21L858R mutations (P=0.41). Conclusions Response depth was not a positive predictor for prognosis in EGFR-mutant NSCLC patients treated with first-line TKIs.