Lanthanum nitrate demonstrated no genotoxicity in the conducted tests.

Given the widespread applications in industrial and agricultural production, the health effects of rare earth elements (REEs) have garnered public attention, and the genotoxicity of REEs remains unclear. In this study, we evaluated the genetic effects of lanthanum nitrate, a typical representative of REEs, with guideline-compliant in vivo and in vitro methods. Genotoxicity assays, including the Ames test, comet assay, mice bone marrow erythrocyte micronucleus test, spermatogonial chromosomal aberration test, and sperm malformation assay were conducted to assess mutagenicity, chromosomal damage, DNA damage, and sperm malformation. In the Ames test, no statistically significant increase in bacterial reverse mutation frequencies was found as compared with the negative control. Mice exposed to lanthanum nitrate did not exhibit a statistically significant increase in bone marrow erythrocyte micronucleus frequencies, spermatogonial chromosomal aberration frequencies, or sperm malformation frequencies compared to the negative control (P > 0.05). Additionally, after a 24-h treatment with lanthanum nitrate at concentrations of 1.25, 5, and 20 µg/ml, no cytotoxicity was observed in CHL cells. Furthermore, the comet assay results indicate no significant DNA damage was observed even after exposure to high doses of lanthanum nitrate (20 µg/ml). In conclusion, our findings suggest that lanthanum nitrate does not exhibit genotoxicity.

Impact of hyperglycemia on tuberculosis treatment outcomes: a cohort study.

Hyperglycemia is prevalent and closely associated with pulmonary tuberculosis (PTB). This study aimed to investigate the effects of hyperglycemia on the outcomes of PTB treatment. This study comprised 791 patients with PTB in total. Patients with fasting plasma glucose levels of ≥ 6.1 mmol/L were diagnosed with hyperglycemia. Anthropometric and baseline demographic data were also collected. The treatment response was assessed based on clinical symptoms (sputum production, cough, chest pain, fever, hemoptysis, night sweats, loss of appetite, and fatigue), sputum smear, chest computed tomography (CT), and adverse gastrointestinal responses (vomiting, nausea, abdominal distension, diarrhea, and constipation). A generalized estimating equation (GEE) was used to evaluate these relationships. Hyperglycemia affected 266 (33.6%) of the 791 patients with PTB. In GEE analyses, patients with hyperglycemia exhibited a greater incidence of elevated tuberculosis (TB) scores (odds ratio (OR) 1.569; 95% CI 1.040-2.369), cough (OR 1.332; 95% CI 1.050-1.690), and night sweats (OR 1.694; 95% CI 1.288-2.335). Hyperglycemia was linked with a higher risk of positive sputum smears (OR 1.941; 95% CI 1.382-2.727). During therapy, hyperglycemia was also associated with an increased incidence of vomiting (OR 2.738; 95% CI 1.041-7.198), abdominal distension (OR 2.230; 95% CI 1.193-4.171), and constipation (OR 2.372; 95% CI 1.442-3.902). However, the CT results indicated that hyperglycemia did not affect pulmonary lesions in patients with TB. Patients with TB and hyperglycemia are at a higher risk of severe clinical manifestations, positive sputum smears, and adverse gastrointestinal effects and, therefore, the special situation of hyperglycemic patients should be considered in the prevention and treatment of TB.

Study on the Expression and Potential Function of LncRNA in Peripheral Blood of Patients with Ankylosing Spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is an autoimmune disease that has the characteristics of difficult early diagnosis and a high disability rate. OBJECTIVE: The objective of this study was to further explore the possible mechanism and potential function of lncRNA in AS. METHODS: We used lncRNA microarray technology to detect the expression of lncRNA and mRNA in patients with active AS, stable patients, and healthy controls (HC). Afterward, bioinformatics analysis was conducted on differentially expressed genes. Seven differentially expressed lncRNAs were screened out for real-time fluorescent quantitative PCR (RT-qPCR), combined with various clinical indicators for correlation analysis, and the receiver operating characteristic (ROC) curve was used to analyze the potential of lncRNA as a diagnostic marker for AS. RESULTS: The results showed that the expression levels of NR-037662 and ENST00000599316 in the AS subgroups were significantly higher than those in the HC group, while the expression levels of ENST00000577914 and ENST00000579003 were lower than those in the HC group. The expression levels of NR-003542 and ENST00000512051 in the ASA group were significantly higher than those in the ASS and HC groups, while NR-026756 was just the opposite. Spearman's correlation analysis showed that the expression level of NR-003542 was positively correlated with Bath Ankylosing Spondylitis Functional Index (BASFI), Erythrocyte Sedimentation Rate (ESR), and high sensitivity C-Reactive Protein (hsCRP). The expression level of NR-026756 was negatively correlated with the Bath Ankylosing Spine Inflammatory Disease Activity Index (BASDAI), BASFI, ESR, hsCRP, and globulin (GLOB). In addition, it was also found that the ROC curve analysis of the 4 lncRNAs between the AS group (ASA group and ASS group) and the HC group were statistically significant, and the area under the curve (AUC) of NR-037662, ENST00000599316, ENST00000577914, and ENST00000579003 was 0.804, 0.812, 0.706, and 0.698, respectively. CONCLUSION: It was found that these differentially expressed lncRNAs of AS may be involved in the occurrence and development of the disease. Among them, NR-037662, ENST00000599316, ENST00000577914, and ENST00000579003 might have the potential to become AS diagnostic molecular markers. Moreover, NR -003542, ENST00000512051, and NR-026756 might have the potential to be indicators of disease activity.

Application value of ultrasound elastography for screening of early pregnancy cervical insufficiency: a retrospective case-control study.

OBJECTIVE: This study aimed to investigate changes in the cervical strain rate (SR), cervical length (CL), and uterine artery blood flow parameters during early pregnancy in women with cervical insufficiency and evaluate the clinical efficacy of these markers for screening of cervical insufficiency in early pregnancy. METHODS: This retrospective study in 60 pregnant women with cervical insufficiency and 100 normal pregnant women was conducted between September 2021 and January 2023 and measured ultrasound parameters of the cervix during early pregnancy. The cervical SR, CL, and uterine artery resistance index (RI) were measured in both groups at 11-14 weeks of gestation. Strain elastography represented by the SR was used to assess the hardness of the internal and external cervical openings. RESULTS: During early pregnancy, the SR at the internal and external cervical openings were significantly higher in the cervical insufficiency group than those in the normal pregnancy group (SR I: 0.19 ± 0.018% vs. 0.16 ± 0.014%; SR E: 0.26 ± 0.028% vs. 0.24 ± 0.025%; p < .001). The CL was significantly shorter in the cervical insufficiency group than that measured in the normal pregnancy group (34.3 ± 2.9 mm vs. 35.2 ± 1.99 mm; p = .036), while cervical blood perfusion was also poorer in the cervical insufficiency group than that in the normal pregnancy group (uterine artery RI: 0.76 ± 0.07 vs. 0.74 ± 0.05; p = .048). Receiver operating characteristic (ROC) curve analysis showed that the optimal critical values for diagnosing cervical insufficiency were 0.17% for SR I, 0.25% for SR E, 33.8 mm for CL, and 0.78 for uterine artery RI. Of these parameters, the ROC curve for SR I had the largest area under the curve [AUC = 0.89 (p < .001)], with the highest sensitivity (78%) and specificity (82%). Multivariate logistic regression analysis demonstrated that the SR at the internal cervical opening (OR 17.47, 95% confidence interval (CI) 5.08-60.08; p < .001) and CL (OR 5.05, 95% CI 1.66-15.32; p = .004) still showed significant differences between the two groups. CONCLUSION: Cervical elastography is an effective tool for screening early pregnancy cervical insufficiency. The SR at the internal cervical opening is a valuable indicator for screening cervical insufficiency and has superior clinical efficacy for screening for this condition compared to that of CL and the uterine artery blood flow index.

Seasonal dynamics response mechanism of benthic microbial community to artificial reef habitats.

Artificial reefs (ARs) have been globally deployed to enhance and restore coastal resource and ecosystems. Microorganisms play an essential role in marine ecosystems, while the knowledge regarding the impact of ARs on microecology is still limited, particularly data concerning the response of benthic microbial community to AR habitats. In this study, the seasonal dynamics of benthic microbial community in AR and adjacent non-artificial reef (NAR) areas surrounding Xiaoshi Island were investigated with high-throughput sequencing technology. The results revealed that the diversity and structure of microbial community between AR and NAR both displayed pronounced seasonal dynamics. There was a greater influence of season factors on microbial communities than that of habitat type. The microbial communities in AR and NAR habitats were characterized by a limited number of abundant taxa (ranging from 5 to 12 ASVs) with high relative abundance (8.35-25.53%) and numerous rare taxa (from 5994 to 12412 ASVs) with low relative abundance (11.91%-24.91%). Proteobacteria, Bacteroidota and Desulfobacterota were the common predominant phyla, with the relative abundances ranging from 50.94% to 76.76%. A total of 52 biomarkers were discovered, with 15, 4, 6, and 27 biomarkers identified in spring, summer, autumn and winter, respectively. Co-occurrence network analysis indicated that AR displayed a more complex interaction pattern and higher susceptibility to external disturbances. Furthermore, the neutral model and ßNTI analyses revealed that the assembly of microbial communities in both AR and NAR is significantly influenced by stochastic processes. This study could provide valuable insights into the impact of ARs construction on the benthic ecosystems and would greatly facilitate the development and implementation of the future AR projects.

Curative Effect Observation of Burosumab for Children and Adults with X-Linked Hypophosphatemicrickets / 罕见病研究

We studied the patients diagnosed with X-linked hypophosphatemicrickets(XLH) and treated with burosumab in Peking Union Medical College Hospital from January 2021 to December 2022. In addition, we described the clinical characteristics of the patients, the changes of clinical indexes before and after burosumab treatment, and the adverse drug reactions during treatment. We also evaluated the efficacy and safety of burosumab for XLH. The results showed that three children XLH patients and one adult XLH patients received burosumab treatment. After treatment, the serum phosphorus level of all patients increased; the serum phosphorus of 3 children patients increased above the lower limit of the reference value range; the serum alkaline phosphatase(ALP) of all patients was lower than that of before treatment; the serum ALP of one adult patient was close to the normal range after 2.5 years of treatment. One child patient showed small crystals in kidney through ultrasound 48 weeks after treatment; one child and one adult showed increased serum parathyroid hormone(PTH)level before treatment and serum PTH continued increasing after treatment. Finally, it may be concluded that burosumab increased serum phosphorus levels in XLH patients, kept the level relatively stable, and reduced serum ALP levels. No serious adverse reactions occurred during treatment, in order to provide reference for the use of burosumab in patients with XLH.

Relationship Among Fungal Diversity at Different Levels of Root System of Stellaria dichotoma var. lanceolata， Soil Properties， and Main Components of Medicinal Materials in Lithosol Habitats / 中国实验方剂学杂志

ObjectiveTo explore the interaction among root fungi of Stellaria dichotoma var. lanceolata， soil factors， and main components of medicinal materials in lithosol habitats. MethodHigh-throughput sequencing technology was employed to determine the fungal community of the root system of S. dichotoma var. lanceolata at different levels （bulk soil， rhizosphere soil， rhizoplane soil， and root interior） and the soil properties of the root system （bulk and rhizosphere）， and the relationship among the fungal community， soil properties， and the main components of medicinal materials was analyzed. ResultThe total phosphorus， available phosphorus， alkaline nitrogen， dissolved organic carbon， and soil water content in the rhizosphere soil of S. dichotoma var. lanceolata were slightly higher than those in the rhizosphere， but the difference was not significant. Ascomycota is the dominant phylum of root fungi in S. dichotoma var. lanceolata. In the progressive level of bulk-rhizosphere-rhizoplane-root interior system， although the fungal diversity gradually decreased， the abundance of Hypocreales， a new phylum （unclassified_ k_ Fungi）， Helotiales， and Natipusilales gradually increased， among which Hypocreales is the most important fungal group in the root system of S. dichotoma var. lanceolata. The structural equation model （SEM） shows that the physicochemical factors of the root-soil play an important regulatory role in the fungal community and the main components of medicinal herbs， with soil total nitrogen， alkaline nitrogen， soil water content， and pH being the main regulatory factors. Soil nitrogen content is the key to promoting the main components of the medicinal herbs， and Penicillium fungi are the key fungal group to regulate the main components of the medicinal herbs. ConclusionIt highlights that the physicochemical properties of the soil of S. dichotoma var. lanceolata play a crucial role in the fungal community and the components of medicinal materials. Hypocreales fungi in the root of S. dichotoma var. lanceolata were an important group， and Penicillium fungi had a certain role in mediating the components of medicinal materials.

Improved unilateral puncture PVP based on 3D printing technology for the treatment of osteoporotic vertebral compression fracture / 中国骨伤

OBJECTIVE@#To investigate the clinical effect of unilateral percutaneous vertebroplasty (PVP) combined with 3D printing technology for the treatment of thoracolumbar osteoporotic compression fracture.@*METHODS@#A total of 77 patients with thoracolumbar osteoporotic compression fractures from October 2020 to April 2022 were included in the study, all of which were vertebral body compression fractures caused by trauma. According to different treatment methods, they were divided into experimental group and control group. Thirty-two patients used 3D printing technology to improve unilateral transpedicle puncture vertebroplasty in the experimental group, there were 5 males and 27 females, aged from 63 to 91 years old with an average of (77.59±8.75) years old. Forty-five patients were treated with traditional bilateral pedicle puncture vertebroplasty, including 7 males and 38 females, aged from 60 to 88 years old with an average of(74.89±7.37) years old. Operation time, intraoperative C-arm X-ray times, anesthetic dosage, bone cement injection amount, bone cement diffusion good and good rate, complications, vertebral height, kyphotic angle (Cobb angle), visual analogue scale(VAS), Oswestry disability index (ODI) and other indicators were recorded before and after surgery, and statistically analyzed.@*RESULTS@#All patients were followed up for 6 to 23 months, with preoperative imaging studies, confirmed for thoracolumbar osteoporosis compression fractures, two groups of patients with postoperative complications, no special two groups of patients' age, gender, body mass index (BMI), time were injured, the injured vertebral distribution had no statistical difference(P>0.05), comparable data. Two groups of patients with bone cement injection, bone cement dispersion rate, preoperative and postoperative vertebral body height, protruding after spine angle(Cobb angle), VAS, ODI had no statistical difference(P>0.05). The operative time, intraoperative fluoroscopy times and anesthetic dosage were statistically different between the two groups(P<0.05). Compared with the traditional bilateral puncture group, the modified unilateral puncture group combined with 3D printing technology had shorter operation time, fewer intraoperative fluoroscopy times and less anesthetic dosage. The height of anterior vertebral edge, kyphosis angle (Cobb angle), VAS score and ODI of the affected vertebrae were statistically different between two groups at each time point after surgery(P<0.05).@*CONCLUSION@#In the treatment of thoracolumbar osteoporotic compression fractures, 3D printing technology is used to improve unilateral puncture PVP, which is convenient and simple, less trauma, short operation time, fewer fluoroscopy times, satisfactory distribution of bone cement, vertebral height recovery and kyphotic Angle correction, and good functional improvement.

Discovery of proqodine A derivatives with antitumor activity targeting NAD(P)H: quinone oxidoreductase 1 and nicotinamide phosphoribosyltransferase / 中国天然药物

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD+), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD+ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD+ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.

Experimental investigation on the aero-optical effects of supersonic gas films with various cooling fluids.

Despite the fact that a supersonic cooling gas film can efficiently insulate aerodynamic heating, its interaction with the mainstream generates a sophisticated flow structure which may cause significant aero-optical ramifications. This study aims to analyze the fluid structure and wavefront distortion of supersonic gas film when subjected to varying nozzle pressure ratios (NPR) by employing two distinct cooling refrigerants, namely C O 2 and air. Within the NPR range of 0 to 2, a linear relationship exists between the wavefront distortion of both C O 2 and air films, while the C O 2 film exhibits higher wavefront distortion than the air. Additionally, the influence of condensation on the discrepancies in aero-optical effects of the two refrigerants is discussed.

Nitrogen removal performance of aerobic denitrifying bacteria enhanced by an iron-anode pulsed electric field.

Pulsed electric field (PEF) technology has attracted considerable attention because it can efficiently treat pollutants that are difficult to degrade. In this study, a PEF system using iron as the electrode was constructed to investigate the effect of PEF-Fe on the growth and metabolism of aerobic denitrifying bacteria and the effectiveness of wastewater nitrogen removal. The chemical oxygen demand, NO3--N and nitrate removal rates were 98.93%, 97.60% and 24.40 mg·L-1·h-1, respectively, under optimal conditions. As confirmed in this study, PEF-Fe could improve the key enzyme activities of W207-14. Scanning electron microscopy revealed that the surface of PEF-Fe-treated W207-14 was intact and smooth without any irreversible deformation. Flow cytometry combined with fluorescence staining analysis also confirmed reversible electroporation on the cell membrane surface of PEF-Fe-treated W207-14. Differentially expressed gene enrichment analysis showed that PEF-Fe activated the transmembrane transport function of ATP-binding cassette transporte (ABC) transport proteins and enhanced the cell membrane permeability of aerobic denitrifying bacteria. The significant differential expression of iron-sulphur cluster proteins facilitated the regulation of electron transport and maintenance of the dynamic balance of iron ions within the PEF-Fe system.

Study on signal transmission mechanism of arbuscular mycorrhizal hyphal network against root rot of Salvia miltiorrhiza.

To explore the signal transmission mechanism of the arbuscular mycorrhizal network against root rot of Salvia miltiorrhiza. In this experiment, the arbuscular mycorrhizal hyphal network was established among Salvia miltiorrhiza plants, and a two plant three-compartment culture model was established. The root of the donor Salvia miltiorrhiza was inoculated with the pathogenic fungi Fusarium solani. The changes of hormone signals such as jasmonic acid and salicylic acid and the expression of related defense genes in the recipient Salvia miltiorrhiza plants in different periods were measured, to study the underground disease resistance signal transmission mechanism among medicinal plants. Salvia miltiorrhiza can transmit the signal of resistance to root rot through the jasmonic acid pathway; When plants suffer from disease stress, the content of JA increases significantly, and the increase of JA content will inhibit the content of SA in plants; The gene expression of PR-10 gene in the roots of Salvia miltiorrhiza with arbuscular mycorrhizal network infected by pathogenic fungi was 17.56 times higher than that inoculated only with pathogenic fungi; Changes in hormone content will also cause changes in the expression of related defense genes, such as SnRK2 is inhibited by ABA in the signal transduction pathway, while JA and ABA show antagonistic changes after inoculation of pathogenic fungi in Salvia miltiorrhiza, so JA may positively regulate the expression of SnRK2 gene. Plants can transmit signals through AM hyphal network after being stressed by the pathogen Fusarium solani. In the arbuscular mycorrhizal hyphal network, JA has important significance for the signal transmission of resistance to root rot and disease resistance of Salvia miltiorrhiza, which can make Salvia miltiorrhiza ready for stress resistance and improve the stress resistance of Salvia miltiorrhiza. This experiment is of great significance to further analyze the signal transmission mechanism of the arbuscular mycorrhizal hyphal network.

Concerned About the Shortage of Paediatricians in Developing Countries.

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Ion-Dipole Interaction Enabling Highly Efficient CsPbI3 Perovskite Indoor Photovoltaics.

Metal halide perovskites are ideal candidates for indoor photovoltaics (IPVs) because of their easy-to-adjust bandgaps, which can be designed to cover the spectrum of any artificial light source. However, the serious non-radiative carrier recombination under low light illumination restrains the application of perovskite-based IPVs (PIPVs). Herein, polar molecules of amino naphthalene sulfonates are employed to functionalize the TiO2 substrate, anchoring the CsPbI3 perovskite crystal grains with a strong ion-dipole interaction between the molecule-level polar interlayer and the ionic perovskite film. The resulting high-quality CsPbI3 films with the merit of defect-immunity and large shunt resistance under low light conditions enable the corresponding PIPVs with an indoor power conversion efficiency of up to 41.2% (Pin : 334.11 µW cm-2 , Pout : 137.66 µW cm-2 ) under illumination from a commonly used indoor light-emitting diode light source (2956 K, 1062 lux). Furthermore, the device also achieves efficiencies of 29.45% (Pout : 9.80 µW cm-2 ) and 32.54% (Pout : 54.34 µW cm-2 ) at 106 (Pin : 33.84 µW cm-2 ) and 522 lux (Pin : 168.21 µW cm-2 ), respectively.

Comparative analysis of clinical efficacy between laparoscopic and open pancreaticoduodenectomy.

Laparoscopic pancreaticoduodenectomy (LPD) is a technically demanding procedure but is gradually gaining acceptance in clinical practice. This study was performed to compare the short-term outcomes of LPD with open pancreaticoduodenectomy (OPD). The perioperative data of the patients who underwent LPD (n = 25) and OPD (n = 40) from January 1, 2017 to December 31, 2021 at Zhangjiagang Hospital Affiliated to Soochow University were collected and retrospectively analyzed. All patients received R0 resection, and none of the patients died within the perioperative period. The preoperative data (gender, age, body mass index [BMI], and preoperative bilirubin), the intraoperative data (operative time, number of retrieved lymph nodes), and postoperative data (level 1 monitoring time, postoperative fluid diet time, postoperative fluid feeding time, and hospitalization cost) were comparable between the 2 groups (P > .05). The estimated blood loss, abdominal drainage tube removal time, postoperative hospital stay, catheter removal time, and analgesic drug use were significantly lesser in the LPD group, when compared to the OPD group (P < .05). LPD is safe and feasible. Compared to OPD, LPD has less surgical trauma, less intraoperative bleeding, and faster postoperative recovery.

Early arrival did not ensure the early acquisition of intravenous thrombosis for acute ischemic stroke during the COVID-19 pandemic.

BACKGROUND: Intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) is a time-dependent treatment with a narrow therapeutic time window, in which the time delay could result from the deadline effect. METHODS: One hospital-based cohort was recruited to detect the factors contributing to the deadline effect, where patients with the deadline effect were defined as those who were presented with the onset-to-door time (ODT) in the first 50%, while the door-to-needle time (DNT) was in the last quartile. DNT (in-hospital delay) was further subdivided into several time intervals [door-to-examination time (DET), door-to-imaging time (DIT), door-to-laboratory time (DLT), and decision-making time (DMT) of the patients or their proxies. RESULTS: A total of 186 IVT cases were enrolled, of which 17.2% (32/186) suffered a delay of the deadline effect. The median age was 66 years, and 35.5% were female. Baseline characteristics were similar between the two groups (all p > .05). For the comparisons of the time intervals, DIT (26 versus 15 min, p = .001) was significantly longer in the group with deadline effect, while the differences of DET, DLT, DMT, and ONT did not reach statistical significance (all p > .05). Upon multivariable adjustment in the binary logistic regression model, longer DIT [odds ratio (OR), 1.076; 95% confidence interval (CI), 1.036-1.118; p < .001], and history of coronary heart disease (OR, 3.898; 95%CI, 1.415-10.735; p = .008) were independently associated with deadline effect in the binary logistic regression model, while admitted in the working day (OR, 0.674; 95%CI, 0.096-0.907; p = .033), and having medical insurance (OR, 0.350; 95% CI, 0.132-0.931; p = .035) were negatively associated with the deadline effect. CONCLUSIONS: A speed-safety tradeoff phenomenon from the deadline effect was observed in 17.2% of IVT cases during the COVID-19 pandemic, where longer DIT contributed a lot to this time delay. Patients without medical insurance, or admitted in official holidays were more likely to experience a delay of the deadline effect.

Study on the efficacy and influencing factors of pyrotinib in treatment of patients with human epidermal growth factor receptor 2-positive metastatic breast cancer / 肿瘤研究与临床

Objective:To evaluate the efficacy of oral pyrotinib in treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in the real world, and to explore its influencing factors.Methods:The clinical data of 148 patients with HER2-positive metastatic breast cancer treated with oral pyrrolitinib in Shanxi Cancer Hospital from September 2018 to December 2020 were retrospectively analyzed. The efficacy was evaluated according to the efficacy evaluation criteria for solid tumors, version 1.1, and the adverse effects were graded according to the National Cancer Institute common terminology criteria of adverse effects, version 4.0. The Kaplan-Meier method was used to draw progression-free survival (PFS) curves, the patients were stratified by different clinical characteristics, and log-rank test was used for univariate analysis of PFS; the multivariate analysis of PFS was performed using Cox proportional hazards model.Results:The objective response rate (ORR) of 148 patients was 71.6% (106/148), and the disease control rate (DCR) was 89.2% (132/148). The overall median PFS time was 11.0 months (95% CI 10.1-11.9 months), and the median PFS of 19 patients with brain metastases was 10.0 months (95% CI 7.4-12.6 months). The differences in PFS between patients stratified by disease-free interval (DFI), the number of metastatic site and Eastern Cooperative Oncology Group (ECOG) score were statistically significant (all P < 0.05), but the difference in PFS between patients with negative and positive hormone receptor was not statistically significant ( P > 0.05). Multivariate Cox regression analysis showed that DFI (>1 year vs. ≤1 year: HR = 5.254, 95% CI 0.728-37.933, P = 0.046) and ECOG score (≥2 points vs. 0-1 point: HR = 2.454, 95% CI 1.261-4.788, P = 0.008) were independent influencing factors of PFS. The most common ≥grade 3 adverse effects were diarrhea (31 cases, 20.9%) and hand-foot syndrome (38 cases, 25.8%). Conclusions:The pyrotinib has definite efficacy and good safety in the treatment of HER2-positive metastatic breast cancer in the real world, especially for patients with DFI > 1 year and ECOG score 0-1 point, the efficacy and safety are particularly good.

Prognostic value of serum cystatin C levels on kidney outcome in type 2 diabetes mellitus patients complicated with chronic kidney disease / 中华检验医学杂志

Objective:We aimed to explore the prognostic value of serum cystatin C (CysC) levels on kidney disease outcome in type 2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD).Methods:The clinical data and pathological examination results of 113 T2DM patients with CKD, who were hospitalized in the First Affiliated Hospital of Nanjing Medical University from January 2011 to July 2020, were retrospectively analyzed in this study. Clinicopathological features and renal outcomes were compared between patients with CysC>1.54 mg/L ( n=57) and CysC≤1.54 mg/L ( n=56) at the time of renal biopsy. Cox regression analysis was used to analyze the risk factors of poor renal prognosis. The relationship between serum CysC level and renal prognosis was analyzed by smoothing curve fitting and threshold effect. Kaplan-Meier survival curve was used to compare and analyze the difference of renal survival rate. Further, the receiver operator characteristic curve was used to evaluate the predictive value of serum CysC combined with renal tubular marker blood and urinary neutrophil gelatinase-associated lipocalin (NGAL) on renal prognosis in all enrolled patients and those with different kidney disease stages. Besides, the ability of serum CysC level to predict renal prognosis within 3 years was evaluated by time-dependent area under the curve (AUC). Results:Compared with patients with serum CysC levels≤1.54 mg/L, patients with CysC>1.54 mg/L had more deteriorated renal function, decreased levels of hemoglobin and serum 25(OH) vitamin D, but more severe interstitial inflammation, higher glomerular sclerosis ratio and severe vascular lesion (all P<0.05). During 36.77 (29.34, 44.20) months follow-up, the composite renal outcomes were noted in 37.2% patients. Kaplan-Meier survival curve showed that the cumulative survival rates of patients without renal end points was significantly lower in CysC level>1.54 mg/L group than in CysC≤1.54 mg/L group (χ 2=5.752, P=0.016). Adjusted multivariate Cox analysis showed that serum CysC level ( HR=7.850, 95% CI 1.248-49.382, P<0.05) was an independent risk factor for renal prognosis. Smoothing curve fitting analysis showed that there was a linear relationship between serum CysC level and relative risk of renal endpoint event (β=2.25, 95% CI 1.06-4.81, P=0.036). The time-dependent receiver operator characteristic curve showed that the AUC of serum CysC in predicting the poor renal prognosis of T2DM patients within 3 years after renal biopsy were 0.714, 0.625 and 0.631, respectively. The AUC of serum CysC combined with blood and urinary NGAL was 0.694 (sensitivity 55.56%, specificity 77.78%). In the population with eGFR less than 60 ml·min -1·1.73m -2 ( n=51), the AUC was 0.817 (sensitivity 66.67%, specificity 85.00%). Conclusions:Higher serum CysC level is associated with deteriorated renal function, more severe renal pathological lesions and increased risk of worse renal prognosis in T2DM patients. Serum CysC level presents better predictive value for the renal prognosis of T2DM patients within 1 year after renal biopsy. Combined with renal tubular marker blood and urinary NGAL, serum CysC level might serve as a potential tool for identifying cases with high-risk of unsatisfactory renal prognosis, especially in those with eGFR less than 60 ml·min -1·1.73m -2.

Effect of complete percutaneous revascularization on improving long-term outcomes of patients with chronic total occlusion and multi-vessel disease / 中华医学杂志(英文版)

BACKGROUND@#Limited data are available on the comparison of clinical outcomes of complete vs. incomplete percutaneous coronary intervention (PCI) for patients with chronic total occlusion (CTO) and multi-vessel disease (MVD). The study aimed to compare their clinical outcomes.@*METHODS@#A total of 558 patients with CTO and MVD were divided into the optimal medical treatment (OMT) group ( n = 86), incomplete PCI group ( n = 327), and complete PCI group ( n = 145). Propensity score matching (PSM) was performed between the complete and incomplete PCI groups as sensitivity analysis. The primary outcome was defined as the occurrence of major adverse cardiovascular events (MACEs), and unstable angina was defined as the secondary outcome.@*RESULTS@#At a median follow-up of 21 months, there were statistical differences among the OMT, incomplete PCI, and complete PCI groups in the rates of MACEs (43.0% [37/86] vs. 30.6% [100/327] vs. 20.0% [29/145], respectively, P = 0.016) and unstable angina (24.4% [21/86] vs. 19.3% [63/327] vs. 10.3% [15/145], respectively, P = 0.010). Complete PCI was associated with lower MACE compared with OMT (adjusted hazard ratio [HR] = 2.00; 95% confidence interval [CI] = 1.23-3.27; P = 0.005) or incomplete PCI (adjusted HR = 1.58; 95% CI = 1.04-2.39; P = 0.031). Sensitivity analysis of PSM showed similar results to the above on the rates of MACEs between complete PCI and incomplete PCI groups (20.5% [25/122] vs. 32.6% [62/190], respectively; adjusted HR = 0.55; 95% CI = 0.32-0.96; P = 0.035) and unstable angina (10.7% [13/122] vs. 20.5% [39/190], respectively; adjusted HR = 0.48; 95% CI = 0.24-0.99; P = 0.046).@*CONCLUSIONS@#For treatment of CTO and MVD, complete PCI reduced the long-term risk of MACEs and unstable angina, as compared with incomplete PCI and OMT. Complete PCI in both CTO and non-CTO lesions can potentially improve the prognosis of patients with CTO and MVD.