Variation in neuroimaging and outcomes in patients with Sturge Weber syndrome Type III.

OBJECTIVES: Sturge Weber syndrome (SWS) is a neurovascular condition with an estimated incidence of 1 in 20,000 to 50,000 live births. SWS Types I and II involve cutaneous and ophthalmological findings, with neurological involvement in Type I. SWS Type III is exclusive to brain stigmata. Our study aims to describe the characteristics of brain MRI findings and report neuroradiological features with seizure and cognitive outcomes in patients with SWS Type III. METHODS: This is a retrospective case series examining the clinical, radiological, and cognitive characteristics of patients with SWS Type III referred to the SWS Clinic at Boston Children's Hospital. We analyzed brain MRI findings based on vascular and parenchymal features. Clinical and cognitive outcomes were based on a validated assessment tool in this population (Neuroscore). RESULTS: This dedicated case series of patients with Type III SWS from a single center identified ten patients. All patients had classic stigmata indicative of SWS. Two distinct radiological phenotypes were found, one characterized by more pronounced deep venous enlargement, and the other, with more pronounced parenchymal abnormalities. There was heterogeneity in seizure presentation and outcome. Earlier age of onset and seizures predict more severe outcomes, as seen in classic SWS. CONCLUSION: We could not find significant divergence in outcomes between patients with differing neuroimaging phenotypes. These results raise the question of whether the two distinct radiological phenotypes found in SWS Type III are reflective of different disease entities, with underlying genetic heterogeneity. These results suggest the need for larger, multi-center natural history studies.

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.

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.

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.

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.

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.

Concerned About the Shortage of Paediatricians in Developing Countries.

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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.

Establishment of a novel co-cultured liver cancer model based on tumor microenvironment / 中华肿瘤杂志

Objective: To construct a new co-cultured liver cancer research model composed of activated hepatic stellate cells (aHSC) and liver cancer cells, explore the efficacy difference between it and traditional model, so as to establish a liver cancer research model in vitro and in vivo that can reflect the real clinical efficacy. Methods: A new co-culture model of liver cancer consisting of aHSC and liver cancer cells was constructed. The differences in efficacy between the new co-culture model and the traditional single cell model were compared by cytotoxicity test, cell migration test, drug retention test and in vivo tumor inhibition test. Western blot was used to detect the drug-resistant protein P-gp and epithelial-mesenchymal transition-related proteins. Masson staining was used to observe the deposition of collagen fibers in tumor tissues of tumor-bearing mice. CD31 immunohistochemical staining was used to observe the microvessel density in tumor tissues of tumor-bearing mice. Results: The cytotoxicity of single cell model and co-culture model was dose-dependent. With the increase of curcumin (CUR) concentration, the cell viability decreased, but the cell viability of single cell model decreased faster than that of co-culture model. When the concentration of CUR was 10 μg/ml, the cell viability of the co-culture model was 62.3% and the migration rate was (28.05±3.68)%, which were higher than those of the single cell model [38.5% and (14.91±5.92)%, both P<0.05]. Western blot analysis showed that the expressions of P-gp and vimentin were up-regulated in the co-culture model, which were 1.55 and 2.04 fold changes of the single cell model, respectively. The expression of E-cadherin was down-regulated, and the expression level of E-cadherin in the single cell model was 1.17 fold changes of the co-culture model. Drug retention experiment showed that the co-culture model could promote drug efflux and reduce drug retention. In vivo tumor inhibition experiment showed that the m-HSC+ H22 co-transplantation model had faster tumor growth and larger tumor volume than those of the H22 single cell transplantation model. After CUR treatment, the tumor growths of m-HSC+ H22 co-transplantation model and H22 single cell transplantation model were inhibited. Masson staining showed that the deposition of collagen fibers in tumor tissues of m-HSC+ H22 co-transplantation model mice was more than that of H22 single cell transplantation model. CD31 immunohistochemical staining showed that the microvessel density in tumor tissue of m-HSC+ H22 co-transplantation model was higher than that of H22 single cell transplantation model. Conclusions: The aHSC+ liver cancer cell co-culture model has strong proliferation and metastasis ability and is easy to be resistant to drugs. It is a new type of liver cancer treatment research model superior to the traditional single cell model.

Correlation analysis between post-stroke depression and serum bilirubin and high-sensitivity C-reactive protein / 中国基层医药

Objective:To analyze the influential factors of post-stroke depression and investigate the effects of changes in serum bilirubin and high-sensitivity C-reactive protein on post-stroke depression.Methods:A total of 199 patients with stroke admitted to Qinghai Provincial People's Hospital from December 2019 to December 2020 were included in this study. These patients were divided into the Xining urban group (2 000-3 000 meters above sea level; n = 165) and the Xining prefecture and county group (over 3 000 meters above sea level; n = 34) according to their long-term residence. They were also divided into the post-stroke depression group ( n = 56, including 45 patients in the Xining urban group and 11 patients in the Xining prefecture and county group) and non-post-stroke depression group ( n = 143, including 120 patients in the Xining urban group and 23 patients in the Xining prefecture and county group). Related scales were used to evaluate neurologic deficits and the degree of depression in the two groups. Serum levels of total bilirubin, direct bilirubin, and high-sensitivity C-reactive protein were measured in each group. Neurologic deficits and the degree of depression were correlated with serum levels of total bilirubin, direct bilirubin, and high-sensitivity C-reactive protein. Results:Serum levels of total bilirubin, direct bilirubin, and high-sensitivity C-reactive protein in the post-stroke depression group were (19.95 ± 7.22) mmol/L, (3.98 ± 1.49) mmol/L, and (1.40 ± 2.29) mg/L, respectively, which were significantly higher than (16.20 ± 7.61) mmol/L, (3.19 ± 1.62) mmol/L, and (0.63 ± 1.33) mg/L in the non-post-stroke depression group ( t = 3.17, 3.18, 2.35, all P < 0.05). There was a significant difference in serum level of high-sensitivity C-reactive protein between stroke patients with mild and moderate depression and stroke patients with severe depression ( t = 2.48, P < 0.05). Conclusion:Serum levels of bilirubin and high-sensitivity C-reactive protein play an important role in the pathogenesis of post-stroke depression and there is a significant correlation between the two.

Effects of acupoint application therapy with Chinese medicine combined with tiotropium bromide inhalation on quality of life in patients with stable chronic obstructive pulmonary disease / 中国基层医药

Objective:To investigate the effects of acupoint application therapy with Chinese medicine combined with tiotropium bromide inhalation on quality of life in patients with stable chronic obstructive pulmonary disease (COPD).Methods:A total of 109 patients with stable COPD admitted to People's Hospital of Gaomi from March 2019 to May 2020 were included in this study. They were randomly divided into a control group ( n = 54) and an observation group ( n = 55). Both groups were given tiotropium bromide powder inhalation and acupoint application therapy ( Dazhui, Shenque, Feishu, Pishu, Shenshu and Zusanli). Chinese medicine ointment was applied in the observation group, but not in the control group. All patients were treated for 6 consecutive months. Before and after treatment, pulmonary function indicators [forced expiratory volume in the first second (FEV 1), the percentage of expiratory volume in the first second (FEV 1%), forced vital capacity (FVC), FEV 1/FVC], modified Medical Research Council (mMRC) dyspnea scale score, and the Saint George's Respiratory Questionnaire (SGRQ) score were compared between the two groups before and after treatment to evaluate therapeutic efficacy and quality of life. Results:Before and after treatment, there were no significant differences in FEV 1, FEV 1% and FEV 1/FVC between the two groups (all P > 0.05). After treatment, mMRC score and SGRQ total score in the observation group were (1.91 ± 0.27) points and (38.54 ± 8.18) points, respectively, which were significantly lower than (2.43 ± 0.33) points and (43.12 ± 7.86) points in the control group ( t = 4.93, 4.47, both P < 0.05). The number of exacerbations and the number of hospitalizations were (0.42 ± 0.09) times/6 months and (0.27 ± 0.05) times/6 months in the observation group and they were (0.69 ± 0.17) times/6 months and (0.47 ± 0.13) times/6 months in the control group. There were significant differences in these indices between the two groups ( t = 3.90, 3.85, P < 0.05). Conclusion:Acupoint application therapy with Chinese medicine combined with tiotropium bromide inhalation has a good therapeutic effect on stable COPD. The combined therapy can reduce the number of acute attacks and improve patient's quality of life. This study is scientific and innovative.

Clinical efficacy of in vitro local high-frequency hyperthermia combined with drugs in the treatment of type Ⅲb chronic prostatitis / 现代泌尿外科杂志

【Objective】 To investigate the efficacy of in vitro local high-frequency hyperthermia combined with drugs in the treatment of type Ⅲb chronic prostatitis (CP). 【Methods】 A total of 148 patients with type Ⅲb CP treated in our hospital during Jun.2020 and Jun.2022 were randomly divided into control group (n=74) and combination group (n=74). The control group received only drug treatment, while the combination group received extracorporeal local high-frequency hyperthermia treatment. The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), maximum urinary flow rate (MFR), average urinary flow rate (AFR) and International Index of Erectile Function-5 (IIEF-5) score were compared between the two groups. 【Results】 There were no significant differences between the two groups in terms of NIH-CPSI, MFR, AFR and IIEF-5 score before treatment(P>0.05). After treatment, these indexes increased in both groups (P<0.05), and the improvements in the combination group were more significant (P<0.05). 【Conclusion】 Medication combined with in vitro local high-frequency hyperthermia is effective in improving the clinical symptoms of type Ⅲb CP, which is worth clinical promotion.

Progress in RNA-targeting and Gene Editing Therapies for Transthyretin Amyloidosis Cardiomyopathy / 罕见病研究

Transthyretin(TTR) protein is a tetramer protein, synthesized mainly by the liver. TTR can be misfolded and deposited as amyloid fibrilae and deposited in the myocardial interstroma leading to transthyroxin amyloidosis cardiomyopathy (ATTR-CM). ATTR-CM was included in China's First List of Rare Diseases. Therapeutic strategies for ATTR-CM include blocking TTR synthesis in the liver, stabilizing TTR tetramers and destroying TTR fibra. Small molecule drugs such as tafamidis and diflunisal offer new treatment options for patients. Chlorobenzolic acid became the first drug approved by the U.S. Food and Drug Administration for the treatment of ATTR-CM. Small interfering RNA(siRNA)patisiran and antisense oligonucleotide (ASO)inotersen block TTR expression in the liver and have been approved for the treatment of ATTR variant polyneuropathy (ATTRv-PN)and are in phase Ⅲ trials for the treatment of ATTR-CM. Other siRNA drugs, vutrisiran, and ASO, eplontersen, are being evaluated for clinical efficacy. This article reviews the development of RNA-targeted therapeutics and gene-editing drugs using CRISPR-Cas9.

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.

Clinical efficacy of anterior radius head fracture combined with lateral ligament complex injury / 中华骨科杂志

Objective:To investigate the operation efficacy of anterior radius head fracture combined with lateral ligament complex injury.Methods:The patients with radial head fracture admitted from September 2017 to August 2021 were retrospectively analyzed, 51 males and 54 females, average age of 38.84±13.63 years (range of 16-70 years). Based on the radial head fractures of Mason classification of type II, the cases involving the anterior radius head fracture were divided into three subtypes according to the number of fracture blocks and the type of displacement: type A (53 cases): one part of the anterior radius head collapse fracture; type B (50 cases): two or more parts of the anterior radial head collapse fracture; type C (2 cases): anterior radius head dissociated and displaced fracture. All fractures were treated with open reduction and internal fixation. Among them, the lateral ligament complex of type B were elongated due to the injury but the continuity existed. Therefore, the lateral ligament complex in 21 cases were not repaired in the early period (unrepaired group); in recent years, 29 cases repaired the lateral ligament complex (repair group). The postoperative efficacy was evaluated by elbow range of motion, table-top relocation test, Mayo score, and Broberg Morrey score. the patients were evaluated at final follow-up, except table-top relocation test was recorded according to the actual completion time.Results:All operations were successfully completed. The mean follow-up was 14.08±1.52 months (range of 12-18 months). Type A: the flexion and extension range was 115.70°±6.35°; the completion time of the table-top relocation test was 75.68±11.90 days; the Mayo score was 93.72±2.40 point, and the Broberg Morrey score was 92.89±2.28 point. Type B: lateral ligament repair group (repaired group) 29 cases and unrepaired lateral ligament group (unrepaired group) 21 cases. The flexion and extension range of elbow in repaired group was 112.1°±4.4°, which was better than that in unrepaired group 105.8°±3.7° ( t=5.31, P<0.001). The completion time of table-top relocation test was 77.72±6.51 days in repaired group and 104.29±18.45 days in unrepaired group ( t=6.32, P<0.001). The Mayo score of the repaired group was 90.21±5.88 points and that of the unrepaired group was 87.14±5.26 points ( t=1.90, P=0.063), and there was no significant difference between the two groups. Broberg Morrey score of 90.93±6.43 points in the repaired group was better than 86.95±6.37 points in the unrepaired group ( t=2.17, P=0.035). Type C for 2 patients, the flexion and extension range of elbow were 107°and 106°; the completion time of table-top relocation test were 82 days and 98 days; the Mayo scores were 91 point and 87 point; Broberg Morrey scores were 93 point and 85 point. There was a patient developed myositis ossificans in unrepair group of tybe B. Conclusion:The elbow joint is stable when one part of the anterior radius head collapse fracture; there is a degree of instability in the elbow when two or more parts of the anterior radial head collapse fractures suggest to repair the lateral ligament complex. The elbow joint is extremely unstable when anterior radius head dissociated and displaced fractures, the lateral ligament complex should be repaired in time.

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.