Inetetamab combined with pyrotinib and chemotherapy in the treatment of breast cancer brain metastasis: A case report

BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.

Optimization of communication topology for persistent formation in case of communication faults

To address the optimization problem of communication topology for persistent formation in the case of communication faults such as link interruption,transmitter failure,and receiver failure a two-stage model including fast reconstruction of communication topology and re-optimization of communication topology is constructed.Then,a fast reconstruction algorithm of communication topology for persistent formation(FRA-CT-PF),based on optimally rigid graph,arc addition operation,and path reversal operation,is proposed,which can quickly generate a feasible reconstructed communication topology after communication faults,thus ensuring the safety of the agents and maintaining the formation shape of persistent formation.Furthermore,a re-optimization algorithm of communication topology for persistent formation(ROA-CTPF),based on agent position exchange,is proposed,which can further obtain a reoptimized communication topology to minimize the formation communication cost while still maintaining the formation shape of persistent formation.The time complexities of these two algorithms are also analyzed.Finally,the effectiveness of the above algorithms is verified by numerical experiments.Compared with existing algorithms,FRA-CT-PF can always obtain feasible reconstructed communication topology in much less time under all communication fault scenarios,and ROA-CT-PF can obtain a reoptimized communication topology to further reduce the formation communication cost in a shorter time.

关节镜下髌内侧支持带紧缩术治疗创伤性髌骨不稳的疗效分析

目的探讨关节镜下髌内侧支持带紧缩并外侧支持带松解术治疗创伤性髌骨脱位的疗效。方法 2012年3月-2015年12月收治创伤性髌骨不稳患者17例。其中,男6例,女11例;年龄14~37岁(平均16.8岁)。所有患者在第一次脱位时均有外伤史,术前脱位次数1~4次。术中先进行关节镜检查,评估髌骨轨迹和髌股关节的匹配关系;然后在关节镜监视下紧缩缝合内侧支持带并松解外侧支持带。结果所有患者术后均获随访,随访9~28个月,平均(19.7±1.3)个月。术后无髌骨再脱位发生,恐惧试验阴性,关节活动度均在正常范围。术后CT显示髌股关节解剖关系恢复正常15例,髌骨轻度半脱位2例。术前Lysholm评分为(51.8±4.5)分,术后(92.4±2.8)分。术后1年患膝功能采用Insall评分标准,优11膝,良5膝,可1膝,优良率94.1%。结论关节镜下髌内侧支持带紧缩并外侧松解术治疗创伤性髌骨不稳,具有创伤小、恢复快和复发率低等优点,近期效果可靠。

Influences of blood lipids on the occurrence and prognosis of hemorrhagic transformation after acute cerebral infarction: a case-control study of 732 patients

Background: To study the influence of blood lipid levels on hemorrhagic transformation(HT) and prognosis after acute cerebral infarction(ACI).Methods: Patients with ACI within 72 h of symptoms onset between January 1 st, 2015, and December 31 st, 2016, were retrospectively analyzed. Patients were divided into group A(without HT) and group B(HT). The outcomes were assessed after 3 months of disease onset using the modified Rankin Scale(m RS). An m RS score of 0–2 points indicated excellent prognosis, and an m RS score of 3–6 points indicated poor prognosis.Results: A total of 732 patients conformed to the inclusion criteria, including 628 in group A and 104 in group B. The incidence of HT was 14.2%, and the median onset time was 2 d(interquartile range, 1–7 d). The percentages of patients with large infarct size and cortex involvement in group B were 80.8% and 79.8%, respectively, which were both significantly higher than those in group A(28.7 and 33.4%, respectively). The incidence rate of atrial fibrillation(AF) in group B was significantly higher than that in group A(39.4% vs. 13.9%, P<0.001). The adjusted multivariate analysis results showed that large infarct size, cortex involvement and AF were independent risk factors of HT, while total cholesterol(TC) was a protective factor of HT(OR=0.359, 95% CI 0.136–0.944, P=0.038). With every 1 mmol/L reduction in normal TC levels, the risk of HT increased by 64.1%. The mortality and morbidity at 3 months in group B(21.2% and 76.7%, respectively) were both significantly higher than those in group A(8.0% and 42.8%, respectively). The adjusted multivariate analysis results showed that large infarct size(OR=12.178, 95% CI 5.390–27.516, P<0.001) was an independent risk factor of long-term unfavorable outcomes, whereas low-density lipoprotein cholesterol(LDL-C) was a protective factor(OR=0.538, 95% CI 0.300–0.964, P=0.037). With every 1 mmol/L reduction in normal LDL-C levels, the risk of an unfavorable outcome increased by 46.2%. Major therapies, including intravenous recombinant human tissue plasminogen activator(r TPA), intensive lipid-lowering statins and anti-platelets, were not significantly related to either HT or long-term, post-ACI poor prognosis.Conclusions: For patients with large infarct sizes, especially those with cortex involvement, AF, or lower levels of TC, the risk of HT might increase after ACI. The risk of a long-term unfavorable outcome in these patients might increase with a reduction in LDL-C.

Milligan-Morgan hemorrhoidectomy with anal cushion suspension and partial internal sphincter resection for circumferential mixed hemorrhoids

AIM:To identify a more effective treatment protocol for circumferential mixed hemorrhoids.METHODS:A total of 192 patients with circumferential mixed hemorrhoids were randomized into the treatment group,where they underwent Milligan-Morgan hemorrhoidectomy with anal cushion suspension and partial internal sphincter resection,or the control group,where traditional external dissection and internal ligation were performed.Postoperative recovery and complications were monitored.RESULTS:The time to wound healing was 12.96 ± 2.25 d in the treatment group shorter than 19.58 ± 2.71 d in the control group.Slight pain rate was 58.3% in the treatment group higher than 22.9% in the control group;moderate pain rate was 33.3% in the treatment group lower than 56.3% in the control group severe pain rate was 8.4% in the treatment group lower than 20.8% in the control group.No edema rate was 70.8% in the treatment group higher than 43.8% in the control group;mild local edema rate was 26% in the treatment group lower than 39.6% in the control group obvious local edema was 3.03% in the treatment group lower than 16.7% in the control group.No stenosis rate was 85.4% in the treatment group higher than 63.5% in the control group;moderate stenosis rate was 14.6% in the treatment group Lower than 27.1% in the control group severe anal stenosis rate was 0% in the treatment group lower than 9.4% in the control group.CONCLUSION:Milligan-Morgan hemorrhoidectomy with anal cushion suspension and partial internal sphincter resection is the optimal treatment for circumferential mixed hemorrhoids and can be widely applied in clinical settings.

Manual reduction with traditional small splints for distal radius fracture in older patients

Objective:To investigate the effect of manual reduction with traditional small splints fixation for distal radius fractures in older patients in the emergency department.Methods:Older patients(aged at least 60 years)with distal radius fractures were enrolled in this study.The patients were randomly divided into the treatment group and the control group.The treatment group was treated with manual reduction and small splints fixation.The control group was treated with manual reduction and resin plaster fixation.Before treatment,after reduction,and 3 months after treatment,the palmar tilt angle,ulnar deviation angle,and radial length were recorded.Before treatment and 3 months after treatment,the Cooney wrist joint scores were recorded.The time of fracture healing and related adverse events during the treatment were recorded.Results:Before treatment and after reduction,there were no statistically significant differences between the two groups in palmar tilt angle,ulnar deviation angle,or radial length(P>0.05).Three months after treatment,the palmar tilt angle,ulnar deviation angle,and radial length of the treatment group were better than those of the control group(P<0.05).The Cooney wrist scores of the treatment group was significantly higher than that of the control group three months after the treatment(P<0.05).The time of fracture healing of the treatment group was shorter than that of the control group,but the difference was no statistically significant(P>0.05).Conclusions:Compared with resin plaster fixation,traditional small splints fixation for distal radius fractures in older patients have the advantages of less loss of fracture reduction and faster functional recovery.Besides,the method is simple and low cost thus,it needs to be promoted.

Minimally invasive puncture and drainage or patients with hypertensive spontaneous basal ganglia intracerebral hemorrhage: A prospective non-randomized comparative study of 198 cases

Background: The treatment of hypertensive spontaneous intracranial hemorrhage(ICH) is still controversial. The purpose of the present study was to investigate whether minimally invasive puncture and drainage(MIPD) could provide improved patient outcome compared with decompressive craniectomy(DC).Methods: Eligible, consecutive patients with ICH(≥30 ml, in basal ganglia, within 24 hours of ictus) were nonrandomly assigned to receive MIPD(group A) or to undergo DC(group B) hematoma evacuation. The primary outcome was death at 30 days after onset. Functional independence was assessed at 1 year using the Glasgow Outcome Scale(GOS, scores range from 1 to 5, score 1 indicating death, ≥4 indicating functional independence, with lower scores indicating greater disability). Results: A total of 198 patients met the per protocol analysis(84 cases in group A and 114 cases in group B), including 9 cases lost during follow-up(2 cases in group A and 7 cases in group B). For these 9 patients, their last observed data were used as their final results for intention-to-treat analysis. The mean age of all patients was 57.1 years(range of 31-95 years), and 114 patients were male. The initial Glasgow Coma Scale(GCS) score was 8.1±3.4, and the National Institutes of Health Stroke Scale(NIHSS) score was 20.8±5.3. The mean hematoma volume(HV) was 56.7±23.0 ml(range of 30-144 ml), and there was extended intraventricular hemorrhage(IVH) in 134 patients(67.7%). There were no significant intergroup differences in the above baseline data, except group A had a higher mean age(59.4±14.5years) than the mean age of group B(55.3±11.1 years, P=0.025). The total cumulative mortalities at 30 days and 1 year were 32.3% and 43.4%, respectively, and there were no significant differences between groups A and B(30 days: 27.4% vs. 36.0%, P=0.203; 1 year: 36.1% vs. 48.2%, P=0.112, respectively). However, the mortality for patients ≤60 years, NIHSS【15 or HV≤60 ml was significantly lower in group A than that in group B(all P【0.05). The total cumulative functional independence at 1 year was 26.8%, and the difference between group A(33/43, 39.3%) and group B(20/144, 17.5%) was significant(absolute difference 21.7%, odds ratio [OR] 0.329, 95% confidence interval [CI] 0.171 to 0.631, P=0.001). For patient with severe IVH, the 30 days and 1 year mortality rates were significant lower in group B than those in group A(P=0.025, P=0.036). However, the number of favorable outcomes had no significant difference between groups at 1 year post ictus. Multivariate logistic regression analysis showed that a favorable outcome after 1 year was associated with the difference in therapies(OR 0.280, 95% CI 0.104–0.752, P=0.012), age(OR 0.215, 95% CI 0.069–0.671, P=0.008), GCS(OR 1.187, 95% CI 1.010–1.395, P=0.037), HV(OR 0.943, 95% CI 0.906–0.982, P=0.005), IVH(OR 0.655, 95% CI 0.506–0.849, P=0.001) and PI(OR 0.211, 95% CI 0.071–0.624, P=0.001). Conclusions: Our results suggest that for patients with hypertensive spontaneous ICH(HV≥30 ml in basal ganglia), MIPD may be a more effective treatment than DC, as assessed by a higher rate of functional independence at 1 year after onset as well as reduced mortality in patients ≤60 years of age, NIHSS【15 or HV≤60 ml. For patients with HV 】60 ml, deep coma and severe IVH, the outcomes of the two therapies were similar.

18F-FDG PET/CT in vivo assessment of correlation between vascular calcification and inflammation

Objective:To explore the relationship between calcification of human vascular system and local inflammation using PET/CT.Methods:Patients who were treated with concurrent PET/CT in our hospital were collected continuously,and their arterial image data were analyzed in parallel with standardized uptake values.(SUV)and corresponding slice calcification score(CS)measurement.SUV values were collected and measured for slices with CS greater than 100.Patients were grouped according to CS,and the correlation analysis between SUV values and CS in each group was performed.Results:Overall CS and SUVmax(r=0.62,P<0.05)and SUVmean(r=0.59,P<0.05)were positively correlated,among which CS and SUV values were in the SUVmax(r=0.72,P<0.05),SUVmean(r=0.59,P<0.05),SUVmax of CS 200-299 group(r=0.71,P<0.05),SUVmean(r=0.80,P<0.05),SUVmax of CS 300-399 group(r=0.47,P<0.05),SUVmean(r=0.53,P<0.05)were positively correlated,SUVmax(r=-0.17,P>0.05),SUVmean(r=-0.07,P>0.05)were negatively correlated in CS 400-499 group,CS There was no significant correlation between SUVmax(r=0.22,P>0.05)and SUVmean(r=0.18,P>0.05)in the 500 group.Conclusion:There is a certain correlation between the local vascular calcification area and the corresponding local inflammatory response in the calcification progress PET/CT has the potential to monitor early calcification.

Orientational Chirality,Its Asymmetric Control,and Computational Study

Orientational chirality was discovered and characterized by a C(sp)-C(sp3)axis-anchored chiral center and a remotely anchored blocker.X-ray structural analysis proved that orientatiomers are stabilized by through-space functional groups,making it possible for 1 R-or S-chiral center to exhibit 3 orientational isomers simply by rotating operations.A new model system was proposed,fundamentally different from the traditional Felkin-Ahn-type or Cram-type models.In these traditional models,chiral C(sp^(3))center and blocking C(sp^(3))carbons are connected adjacently,and there exist 6 energy barriers during rotating along the C(sp^(2))-C(sp^(3))axis.In comparison,the present orientational chirality model shows that a chiral C(sp)-C(sp^(3))carbon is remotely located from a blocking group.Thus,it is focused on the steric dialog between a chiral C(sp^(3))center and a remotely anchored functional group.There exist 3 energy barriers for either(R)-or(S)-C(sp)-C(sp^(3))stereogenicity in the new model.Chiral amide auxiliary was proven to be an excellent chiral auxiliary in controlling rotations of orientatiomers to give complete stereoselectivity.The asymmetric synthesis of individual orientatiomers was conducted via multistep synthesis by taking advantage of the Suzuki-Miyaura cross-coupling and Sonogashira coupling reactions.Density functional theory computational study presented optimized conformers and relative energies for individual orientatiomers.This discovery would be anticipated to result in a new stereochemistry topic and have a broad impact on chemical,biomedical,and material sciences in the future.

Design, synthesis and antitumor activity of C3/C3 bis-fluoroquonolones cross-linked with [1,2,4]triazolo[3,4-b] [1,3,4]thiadiazole

To contribute to the development of an efficient method for the conversion of antibacterial fluoroquinolones to antitumor fluoroquinolones,a series of C3/C3 bis-fluoroquinolone fused heterocycles cross-linked with a[1,2,4]-triazolo[3,4-b][1,3,4]-thiadiazole core as a common bioisostere of two carboxylic acid groups was designed and synthesized as their hydrochloride salts.Structures were characterized by elemental analysis and spectral data and their in vitro antitumor activity against L1210,CHO and HL60 cell lines was screened by determination of their IC50 values in the methylthiazole trazolium(MTT)assay.Two compounds were highly potent against the HL60 cell line and represent promising lead compounds for future development.

Temporal and spatial variation in the environmental impacts of China’s resource extraction at the provincial scale

Introduction:Over the past two decades,China has experienced rapid economic development,which has not only led to a rapid increase in the use of raw materials but has also created environmental problems.This research analyzes the environmental impacts of resource extraction in China at the provincial level,and fully considers the environmental impact of various resources extraction.In addition,it is the first time to quantitatively study the spatial pattern and evolution characteristics of the environmental impacts of China’s resource extraction from multiple perspectives by means of spatial visualization.Outcomes:The results showed that the center of gravity of abiotic depletion potential(ADP)moved northwest,respiratory inorganics(RI)moved southwest and global warming potential(GWP)moved west.The results of the standard deviation ellipse showed that RI and GWP varied over time and space,while ADP showed a discrete trend.In addition,the distribution of the four in the northeast-southwest direction became more prominent.Conclusion:To mitigate the environmental impacts of resource extraction,we recommend that regional governments implement measures to control environmental impacts in the provinces within the distributed ellipse and design targeted policies based on actual conditions.

The tumor immune microenvironment transcriptomic subtypes of colorectal cancer for prognosis and development of precise immunotherapy

Background:Biomarkers based on immune context may guide prognosis prediction.T-cell inactivation,exclusion,or dysfunction could cause unfavorable tumor microenvironments,which affect immunotherapy and prognosis.However,none of the immuno-biomarkers reported to date can differentiate colorectal-cancer(CRC)patients.Thus,we aimed to classify CRC patients according to the levels of T-cell activation,exclusion,and dysfunction in the tumor microenvironment.Methods:RNAseq data of 618 CRC patients from The Cancer Genome Atlas and microarray data of 316 CRC patients from Gene Expression Omnibus were analysed using the Tumor Immune Dysfunction and Exclusion algorithm.Unsupervised clustering was used to classify patients.Results:Based on the expression signatures of myeloid-derived suppressor cells,cancer-associated fibroblasts,M2-like tumor-associated macrophages,cytotoxic T-lymphocytes,and PD-L1,all patients were clustered into four subtypes:cluster 1 had a high level of immune dysfunction,cluster 2 had a low level of immune activation,cluster 3 had intense immune exclusion,and cluster 4 had a high level of immune activation and a moderate level of both dysfunction and exclusion signatures.Compared with cluster 1,the hazard ratios and 95%confidential intervals for overall survival were 0.63(0.35-1.13)for cluster 2,0.55(0.29-1.03)for cluster 3,and 0.30(0.14-0.64)for cluster 4 in multivariate Cox regression.Similar immune clustering and prognosis patterns were obtained upon validation in the GSE39582 cohort.In subgroup analysis,immune clustering was significantly associated with overall survival among stage I/II patients,microsatellite stable/instability-low patients,and patients not treated with adjuvant therapy.Conclusions:Our findings demonstrated that classifying CRC patients into different immune subtypes serves as a reliable prognosis predictor and may help to refine patient selection for personalized cancer immunotherapy.