Objective To investigate short-term clinical efficacy of autologous leukocyte-poor platelet-rich plasma(LP-PRP)treatment of knee osteoarthritis(KO A).Methods 85 cases of patients with Keligren Lawrence grade Ⅰ-Ⅲ knee os-teoarthritis in Peking University First Hospital Taiyuan Hospital(Taiyuan Central Hospital)from 2022 to 2023 were collect-ed for autologous LP-PRP collection and quality assessment using a blood component separator,and all patients were treated with autologous LP-PRP.The degree and function of knee pain were assessed by visual analog scale(VAS)and knee arthri-tis index scale(WOMAC)at 1,3 and 6 months after injection.Knee MRI was performed after 6 months of treatment,and the MRI imaging changes before and after treatment were compared.Different influencing factors in the treatment results were grouped and analyzed,mainly including platelet concentration in LP-PRP and K-L grading of knee joint.According to the platelet concentration in LP-PRP,it was divided into three grades,which are low concentration[(＜800)×109/L],medium concentration[(800-1 000)×109/L],and high concentration[(＞1 000)× 109/L];According to the K-L grade of the knee joint,the severity of knee osteoarthritis was divided into three grades:Ⅰ、Ⅱ、Ⅲ.Results The VAS and WOMAC scores at 1,3 and 6 months after LP-PRP treatment were significantly lower than those before treatment,and the difference was sta-tistically significant(P＜0.05).There was a statistically significant difference in the therapeutic effect of different levels of platelet concentration,and when the platelet concentration was more than 1 000×109/L,the significant effect was the most obvious(P＜0.05).The therapeutic effect of different levels of platelet concentration was statistically significant(P＜0.05).MRI showed that the articular cartilage signal was significantly improved after treatment.Conclusion Autologous LP-PRP injection into knee cavity for the treatment of KO A has a good short-term clinical effect in relieving knee pain.

Endocrine therapy is the most important adjuvant treatment for early estrogen receptor(ER)-positive breast cancer.ER-low-positive(immunohistochemistry staining 1%-10%)breast cancer has drawn widespread attention in recent years.This group accounts for 3%-9%of overall breast cancer patients.The efficacy of endocrine adjuvant therapy is relatively limited in patients with ER-low-positive breast cancer.Although the proportion of patients with low ER expression in breast cancer population is relatively low,the clinical needs of this population can not be ignored because of the large number of breast cancer patients.A number of studies have suggested that ER-low-positive breast cancer is different from ER-positive breast cancer,and is similar to ER-negative breast cancer in terms of molecular and biological characteristics,clinical features and prognosis.There are still controversies on the benefit and duration of endocrine therapy for early ER-low-positive breast cancer,and there is a lack of evidence from large-scale prospective studies.Multiple retrospective studies and meta-analyses have suggested that ER-low-positive breast cancer may have limited benefit from adjuvant endocrine therapy,and therefore endocrine therapy should be considered with caution in this population.The benefit of adjuvant therapy combined with cyclin-dependent kinase(CDK)4/6 inhibitors is yet to be supported by future data.Some patients with ER-low-positive breast cancer may try adjuvant chemotherapy in consideration of other risk factors.Additionally,clinical trials that test antibody-drug conjugates(such as sacituzumab govitecan and Dato-DXd),poly(ADP-ribose)polymerase(PARP)inhibitors,and immunotherapies for the treatment of early ER-low-positive breast cancer are still ongoing,including the phase Ⅲ ASCENT-05 study evaluating the adjuvant therapy of sacituzumab govitecan combined with pembrolizumab in high-risk human epidermal growth factor receptor 2(HER2)-negative,ER and progesterone receptor(PR)＜10%patients after surgery,the phase Ⅲ SASCIA study evaluating the adjuvant therapy of sacituzumab govitecan in high-risk HER2-negative patients after surgery,and the phase Ⅲ TROPION-Breast 04 study evaluating the neoadjuvant therapy of Dato-DXd combined with durvalumab.In addition,a neoadjuvant treatment for triple-negative breast cancer(TNBC)and ER-low expression breast cancer with olaparib and durvalumab(NCT03594396)is being explored,and the results are worth expecting.This article aimed to introduce the definition,clinical and pathological characteristics,and prognosis of ER-low breast cancer,and expound on the current treatment status and potential therapeutic strategies for HER2-negative,ER-low-positive early breast cancer in the future.

This paper interprets the background, content overview and characteristics, clinical practice significance and disciplinary development of Nursing Standards for Clinical Operation Techniques in Critical Care Ultrasound (hereinafter referred to as the Standards) and puts forward reflections on the clinical application of the Standards, aiming to improve the critical care ultrasound techniques of clinical nursing staff, solve nursing challenges and make clinical nursing ultrasound techniques more scientific, standardized and homogenized.

OBJECTIVE: To investigate the effect of improved nursing strategy on prognosis of older immunosuppressed patients with pneumonia and sepsis. METHODS: A prospective study was conducted. The older immunosuppressed patients with pneumonia and sepsis admitted to the department of intensive care medicine and emergency intensive care unit (ICU) of Peking Union Medical College Hospital from January 2017 to July 2022 were enrolled. In the first stage (from January 2017 to December 2019), patients received the original nursing strategy (original nursing strategy group), including: (1) nurses were randomly assigned; (2) routine terminal cleaning; (3) ICU environmental cleaning twice a day; (4) oral care was performed with chlorhexidine twice a day; (5) original lung physiotherapy [head of bed elevated at 30 degree angle-45 degree angle, maintaining a Richmond agitation-sedation scale (RASS) -2 to 1, sputum aspiration as needed]. After 1 month of learning and training of the modified nursing treatment strategy for nurses and related medical staff, the patients in the second stage (from February 2020 to July 2022) received the improved nursing strategy (improved nursing strategy group). The improved nursing strategy improved the hospital infection prevention and control strategy and lung physical therapy strategy on the basis of the original nursing strategy, including: (1) nurses were fixed assigned; (2) patients were placed in a private room; (3) enhanced terminal cleaning; (4) ICU environmental cleaning four times a day; (5) education and training in hand hygiene among health care workers was improved; (6) bathing with 2% chlorhexidinegluconate was performed once daily; (7) oral care with a combination of chlorhexidine and colistin was provided every 6 hours; (8) surveillance of colonization was conducted; (9) improved lung physiotherapy (on the basis of the original lung physiotherapy, delirium score was assessed to guide early mobilization of the patients; airway drainage was enhanced, the degree of airway humidification was adjusted according to the sputum properties, achieving sputum viscosity grade II; lung ultrasound was also used for lung assessment, and patients with atelectasis were placed in high lateral position and received the lung recruitment maneuver). Baseline patient information were collected, including gender, age, underlying diseases, source of admission, disease severity scores, vital signs, ventilatory parameters, blood gas analysis, life-sustaining treatments, clinical laboratory evaluation, indicators of infection and inflammation, pathogens and drug therapy. The primary outcome was 28-day mortality, and the secondary outcomes were duration of mechanical ventilation, length of ICU stay, and ICU mortality. Multivariate Logistic regression analysis was used to determine the risk factors for 28-day death in older immunosuppressed patients with pneumonia and sepsis. RESULTS: Finally, 550 patients were enrolled, including 199 patients in the original nursing strategy group and 351 patients in the improved nursing strategy group. No significant differences were found in gender, age, underlying diseases, source of admission, disease severity scores, vital signs, ventilatory parameters, blood gas analysis, life-sustaining treatments, clinical laboratory evaluation, indicators of infection and inflammation, coexisting pathogens or drug therapy between the two groups. Compared with patients in the original nursing strategy group, those in the improved nursing strategy group had significantly fewer duration of mechanical ventilation and length of ICU stay [duration of mechanical ventilation (days): 5 (4, 7) vs. 5 (4, 9), length of ICU stay (days): 11 (6, 17) vs. 12 (6, 23), both P < 0.01], and lower ICU mortality and 28-day mortality [ICU mortality: 23.9% (84/351) vs. 32.7% (65/199), 28-day mortality: 23.1% (81/351) vs. 33.7% (67/199), both P < 0.05]. Multivariate Logistic regression analysis showed that the improved nursing strategy acted as an independent protective factor in 28-day death of older immunosuppressed patients with pneumonia and sepsis [odds ratio (OR) = 0.543, 95% confidence interval (95%CI) was 0.334-0.885, P = 0.014]. CONCLUSIONS Improved nursing strategy shortened the duration of mechanical ventilation and the length of ICU stay, and decreased ICU mortality and 28-day mortality in older immunosuppressed patients with pneumonia and sepsis, significantly improving the short-term prognosis of such patients.
Humans ; Aged ; Prospective Studies ; Chlorhexidine/therapeutic use* ; Intensive Care Units ; Pneumonia ; Prognosis ; Sepsis/therapy* ; Inflammation

Objective:To formulate the Nursing standards of clinical practice of critical care ultrasonography (referred to as the Standards), so as to provide recommendations for the application of ultrasound in intensive care nursing practice. Methods:Based on the experience of intensive care ultrasound nursing practice and literature research, combined with the consensus recommendations of intensive care ultrasound, the critical care ultrasound study group formed the first draft of the Standards. After expert interview, consensus discussion, two rounds of Delphi expert letter consultation and other methods, the content of the Standards was revised and improved, and the final draft of the Standards was formed. Results:The Standards included four parts, such as basic application of intensive care ultrasound, nursing evaluation standard of intensive care ultrasound guidance, nursing operation process guided by ultrasound and intensive care ultrasound training. Conclusions:The establishment of Standards is scientific and practical, which can provide guidance for nursing practice of clinical operation technology of critical care ultrasonography.

Objective:To explore the puncture management in hemodialysis patients with difficult new arteriovenous fistula based on the finest evidence-based best practice evidence and evaluate the clinical effects.Methods:A team was formed, according to theoretical framework basing on the evidence of continuous quality improvement model, the best evidence-based interventions were obtained by adopting evidence-based practice. Formulated review indicators, evaluated obstacles and promoting factors in the process of practice, and took corresponding action strategies. From February 2020 to June 2020, 30 patients admitted to the dialysis center of Sir Run Run Shaw Hospital of Zhejiang University were recruited in the baseline review group by convenience sampling method. From September 2020 to January 2021, 30 patients from September 2020 to January 2021 were recruited in the after-effect evaluation group. The baseline review group adopted the original difficult new arteriovenous fistula puncture management scheme, and the after-effect evaluation group adopted the difficult autologous new internal fistula puncture management scheme based on the best evidence. The success rate of one puncture of fistula, the incidence rate of hematoma during puncture and dialysis, the incidence rate of discontinuation of treatment and the compliance with examination indexes were compared in the patients before and after applying for the evidences.Results:Compared with the baseline review group, the success rate of one-time puncture of internal fistula in the aftereffect evaluation group increased from 36.7% (11/30) to 73.3% (22/30), the incidence rate of hematoma during puncture and dialysis were decreased from 33.3%(10/30) to 6.67%(2/30) and 40%(12/30) to 0, the incidence rate of discontinuation of treatment were decreased from 40%(12/30) to3.33% (1/30), the difference was statistically significant ( χ2 values were 6.67-11.88, P<0.05). The implementation rate of review indexes in the aftereffect evaluation group was higher than that in the baseline review group, and the difference was statistically significant ( P<0.05). Conclusions:Evidence-based practice can improve the success rate of difficult new arteriovenous fistula, and reduce the incidence of arteriovenous fistula hematoma, reduce treatment interruption, and better maintain the lifeline of patients.

Amplifying "eat me signal" during tumor immunogenic cell death (ICD) cascade is crucial for tumor immunotherapy. Inspired by the indispensable role of adenosine triphosphate (ATP, a necessary "eat me signal" for ICD), a versatile ICD amplifier was developed for chemotherapy-sensitized immunotherapy. Doxorubicin (DOX), ATP and ferrous ions (Fe²⁺) were co-assembled into nanosized amplifier (ADO-Fe) through π‒π stacking and coordination effect. Meanwhile, phenylboric acid-polyethylene glycol-phenylboric acid (PBA-PEG-PBA) was modified on the surface of ADO-Fe (denoted as PADO-Fe) by the virtue of d-ribose unit of ATP. PADO-Fe could display active targetability against tumor cells via sialic acid/PBA interaction. In acidic microenvironment, PBA-PEG-PBA would dissociate from amplifier. Moreover, high H₂O₂ concentration would induce hydroxyl radical (·OH) and oxygen (O₂) generation through Fenton reaction by Fe²⁺. DOX and ATP would be released from the amplifier, which could induce ICD effect and "ICD adjuvant" to amplify this process. Together with programmed death ligands 1 (PD-L1) checkpoint blockade immunotherapy, PADO-Fe could not only activate immune response against primary tumor, but also strong abscopal effect against distant tumor. Our simple and multifunctional ICD amplifier opens a new window for enhancing ICD effect and immune checkpoint blockade therapy.

Objective:To retrieve, evaluate, and summarize the best evidence for the assessment of gastrointestinal function in critically ill patients by bedside ultrasound.Methods:Guidelines, evidence summaries, group standards, expert consensus, systematic reviews, and randomized controlled trials on the assessment of gastrointestinal function in critically ill patients by bedside ultrasound were retrieved by computer on domestic and foreign guideline websites, society websites and databases based on evidence-based nursing. The search period was from January 1, 2010 to April 30, 2021. The quality of the article was independently assessed by two researchers using the Appraisal of Guidelines for Research and Evaluation Ⅱ and the critical appraisal tool of the Joanna Briggs Institute (JBI) in Australia (2016) . Combined with the judgment of the research team, the data from the article that met the criteria were extracted and the evidence was graded and recommended according to the JBI quality level of evidence system (2014 Edition) .Results:A total of 22 articles were included, involving 5 guidelines, 1 evidence summary, 1 group standard, 6 expert consensuses, 4 systematic reviews, and 5 randomized controlled trials. A total of 33 pieces of evidence were summarized from 6 aspects, namely, the feasibility of nurses applying bedside ultrasound, fundamentals of ultrasound assessment of gastrointestinal tract, ultrasound assessment of gastric contents, ultrasound assessment of gastric motility, ultrasound assessment of bowel, ultrasound guided enteral nutrition program.Conclusions:Nurses who have been systematically trained can use ultrasound to assess gastrointestinal function in critically ill patients in real time. Ultrasound-guided enteral nutrition for critically ill patients needs to be standardized and improved, and many studies need to be carried out.

Chronic hepatitis B (CHB) is often treated with drugs such as interferons and nucleoside (acid)/nucleotide (acid) analogs. While these drugs are effective in controlling the viral loads, they are not able to eliminate hepatitis B virus (HBV) from the body completely. Besides, side effects and drug resistance may by caused by the long-term use of these drugs. Several monoclonal antibodies (McAbs) against HBV, mostly against hepatitis B surface antigen (HBsAg), have been demonstrated with viral neutralization capability and with effective inhibition of HBV replication in relevant animal models. The use of a McAb individually or in combination with another therapy has the potentials to achieve functional cure of CHB. In this review, we summarized the encouraging results from the research and development of anti-HBV McAbs in clinical or pre-clinical development stage, aiming to provide new idea for the treatment of CHB.

Thimerosal has been widely used as a preservative in drug and vaccine products for decades.Due to the strong propensity to modify thiols in proteins,conformational changes could occur due to covalent bond formation between ethylmercury(a degradant of thimerosal)and thiols.Such a conformational change could lead to partial or even complete loss of desirable protein function.This study aims to investigate the effects of thimerosal on the capsid stability and antigenicity of recombinant human papillomavirus(HPV)18 virus-like particles(VLPs).Dramatic destabilization of the recombinant viral capsid upon thimerosal treatment was observed.Such a negative effect on the thermal stability of VLPs preserved with thimerosal was shown to be dependent on the thimerosal concentration.Two highly neutralizing antibodies,13H12 and 3C3,were found to be the most sensitive to thimerosal treatment.The kinetics of antigenicity loss,when monitored with 13H12 or 3C3 as probes,yielded two distinctly different sets of kinetic parameters,while the data from both monoclonal antibodies(mAbs)followed a biphasic expo-nential decay model.The potential effect of thimerosal on protein function,particularly for thiol-containing proteinaceous active components,needs to be comprehensively characterized during formulation development when a preservative is necessary.