Biomaterial-based scaffolds for direct in situ programming of tumor-infiltrating T lymphocytes.

Adoptive cell therapy with tumor-infiltrating T cells (TILs) has generated exciting clinical trial results for the treatment of unresectable solid tumors. However, solid tumors remain difficult targets for adoptively transferred T cells, due in part to poor migration of TILs to the tumor, physical barriers to infiltration, and active suppression of TILs by the tumor. Furthermore, a highly skilled team is required to obtain tumor tissue, isolate and expand the TILs ex vivo, and reinfuse them into the patient, which drives up costs and limits patient access. Here, we describe a cell-free polymer implant designed to recruit, genetically reprogram and expand host T cells at tumor lesions in situ. Importantly, the scaffold can be fabricated on a large scale and is stable to lyophilization. Using a mouse breast cancer model, we show that the implants quickly and efficiently amass cancer-specific host lymphocytes at the tumor site in quantities sufficient to bring about long-term tumor regression. Given that surgical care is the mainstay of cancer treatment for many patients, this technology could be easily implemented in a clinical setting as an add-on to surgery for solid tumors. Furthermore, the approach could be broadened to recruit and genetically reprogram other therapeutically desirable host cells, such as macrophages, natural killer cells or dendritic cells, potentially boosting the antitumor effectiveness of the implant even more.

[The imaging presentations of the fallopian canal cerebrospinal fluid leaking].

Objective: To summarize the imaging presentations of the fallopian canal cerebrospinal fluid leaking (FCCFL). Methods: The high resolution CT (HRCT)and MRI materials of 4 patients (4 ears) with FCCFL confirmed by surgery between August 2016 to November 2023 were retrospectively analyzed. Among these, there were 2 males and 2 females, their ages ranged from 6 to 69 years. Results: All of the FCCFL were unilateral, including 2 on the left and 2 on the right.Clinically, the patients with FCCFL suffered from clear nasal fluid flow, ear tightness, and hearing loss. On CT, all of the affected ears were depicted markedly dilatation of the proximal portion of fallopian canal(FC), the labyrinthine segment and geniculate fossa were involved in 4 cases, and involvement of tympanic segment in 1 case at the same time. The geniculate fossa in the affected side were significantly enlarged, protruding upwards into the tympanic cavity, with one case simultaneously involving the cochlea. On MRI, the hyposignal on T1WI and hypersignal on T2WI or water sequence like cerebrospinal fluid (CSF) were shown in the enlargement FC, without diffusion restriction, and non-enhancing with administration Gadolinium contrast.CSF-like signal effusion was shown in all of the affected tympanum, of which, the CSF-like signal effusion was demonstrated in the area along the superficial petrosal nerve, the right pterygopalatine fossa and the parapharyngeal space. The adjacent intracranial meninges were presented thickening in 3 cases. Conclusion: The imaging appearances of FCCFL present some characteristics:on HRCT, the proximal portions of the affected FC depicts markedly enlargement,especially the geniculate fossa.While they present CSF-like signal, no diffusion restriction, and no enhancement administration, Gadolinium contrast on MRI, accompanying the CSF-like signal effusion in the affected tympanum.

Diabetes in pregnancy: Women's views of care in a multi-ethnic, low socioeconomic population with midwifery continuity-of-care.

BACKGROUND: Diabetes in pregnancy is diagnosed in 6% of pregnancies annually in Aotearoa-New Zealand, disproportionately affecting multi-ethnic, low socio-economic women. Little is known about the care experience of this population within the model of midwifery continuity-of-care, including views of telehealth care. AIM: Increase understanding of the experience of diabetes in pregnancy care, including telehealth, among multi-ethnic, low socio-economic women receiving midwifery continuity-of-care. METHODS: Qualitative interview study with primarily indigenous and migrant women who had diabetes in pregnancy and gave birth 6-18 months previously. Interviewers were matched with participants by ethnicity. Transcripts were analysed using Framework analysis. RESULTS: Participants were 19 women (5 Maori, 5 Pacific Peoples, 5 Asian, 4 European). Data analysis revealed three key themes: 1) 'shock, shame, and adjustment' to the diagnosis 2) 'learning to manage diabetes in pregnancy' and 3) 'preparation for birth and beyond' to the postpartum period. DISCUSSION: Receiving the diagnosis of diabetes in pregnancy was a shock. Managing diabetes during pregnancy was particularly challenging for indigenous and migrant women, who wished for better access to culturally appropriate dietary and lifestyle information. Women appreciated having options of telehealth and face-to-face consultations. Preparation for birth and postpartum diabetes follow-up were areas requiring significant improvement. Challenges were mitigated through care from a consistent diabetes specialist midwife and community-based midwifery continuity-of-care. CONCLUSION: Midwives were the backbone of diabetes in pregnancy care for this multi-ethnic, low socio-economic population. Care could be improved with more culturally appropriate diet and lifestyle information, better birth preparation, and expanded postpartum diabetes support.

Effects of remittances on life expectancy and under-five mortality in sub-Saharan Africa: Evidence using Generalized Method of Moments analysis

The study examined the relationship between financial remittances and health outcomes in 45 sub-Saharan African countries (SSA) using data obtained from the World Development Indicator (WDI) over the period 1990 to 2021. Because of the issue of endogeneity, the System Generalized Method of Moments (SGMM) was adopted to analyze the impact of remittances on life expectancy and infant mortality respectively. The results showed that contrary to expectations, remittances did not significantly improve life expectancy and infant mortality rate in SSA. The life expectancy in the previous year, has a statically significant impact on life expectancy at birth for the current year. Also, the lagged value of infant mortality rate significantly increased under five mortality. Therefore, the study recommends that governments in SSA sub-region should evolve policies aimed at guiding recipients of remittances towards effective utilization with a view to improving social welfare and health outcomes.

L'étude a examiné la relation entre les envois de fonds et les résultats de santé dans 45 pays d'Afrique subsaharienne (ASS) à l'aide des données obtenues à partir de l'indicateur du développement mondial (WDI) sur la période 1990 à 2021. En raison de la question de l'endogénéité, la méthode généralisée du système of Moments (SGMM) a été adopté pour analyser l'impact des envois de fonds sur l'espérance de vie et la mortalité infantile respectivement. Les résultats ont montré que contrairement aux attentes, les envois de fonds n'ont pas amélioré de manière significative l'espérance de vie et le taux de mortalité infantile en ASS. L'espérance de vie de l'année précédente a un impact statiquement significatif sur l'espérance de vie à la naissance de l'année en cours. En outre, la valeur décalée du taux de mortalité infantile a considérablement augmenté chez les enfants de moins de cinq ans. Par conséquent, l'étude recommande que les gouvernements de la sous-région d'ASS élaborent des politiques visant à guider les destinataires des envois de fonds vers une utilisation efficace en vue d'améliorer le bien-être social et les résultats en matière de santé.

Effect of antioxidant procyanidin b2 (pcb2) on ovine oocyte developmental potential in response to in vitro maturation (ivm) and vitrification stress.

BACKGROUND: It was demonstrated that external stress, such as in vitro maturation (IVM) and vitrification process can induce significantly reduced development capacity in oocytes. Previous studies indicated that antioxidants play a pivotal part in the acquisition of adaptation in changed conditions. At present, the role of the natural potent antioxidant PCB2 in response to IVM and vitrification during ovine oocyte manipulation has not been explored. OBJECTIVE: To investigate whether PCB2 treatment could improve the developmental potential of ovine oocytes under IVM and vitrification stimuli. MATERIALS AND METHODS: The experiment was divided into two parts. Firstly, the effect of PCB2 on the development of oocytes during IVM was evaluated. Un-supplemented and 5 ug per mL PCB2-supplemented in the IVM solution were considered as control and experimental groups (C + 5 ug per mL PCB2). The polar body extrusion (PBE) rate, mitochondrial membrane potential (MMP), ATP, reactive oxygen species (ROS) levels and early apoptosis of oocytes were measured after IVM. Secondly, we further determine whether PCB2 could improve oocyte quality under vitrification stress. The survival rate, PBE rate and early apoptosis of oocytes were compared between fresh group, vitrified group and 5 ug per mL PCB2-supplemented in the IVM solution after vitrification (V + 5 ug per mL PCB2). RESULTS: Compared to the control group, adding PCB2 significantly increased PBE rate (79.4% vs. 62.8%, P < 0.01) and MMP level (1.9 +/- 0.08 vs. 1.3 +/- 0.04, P < 0.01), and decreased ROS level (47.1 +/- 6.3 vs. 145.3 +/- 8.9, P < 0.01). However, there was no significant difference in ATP content and early apoptosis. Compared to the fresh group, vitrification significantly reduced oocytes viability (43.0% vs. 90.8%, P < 0.01) as well as PBE rate (24.2% vs. 60.6%, P < 0.05). However, 5 ug per mL PCB2-supplemention during maturation had no effect on survival, PBE or early apoptosis in vitrified oocytes. CONCLUSION: PCB2 could effectively antagonise the oxidative stress during IVM and promote oocyte development. DOI: 10.54680/fr23210110412.

Radiology program director's perspective on a novel hands-on advanced elective.

With the advent of the USMLE Step 1 exam moving to a pass/fail status, Radiology Program Directors (PDs) and Associate Program Directors (APDs) need alternative methods of identifying interested and engaged medical students who are applying to their program. Additionally, undergraduate radiology medical education in the United States varies widely from institution to institution with no universal mandatory radiology component. To address these problems, we implemented an advanced fourth year hands-on radiology elective where the students were treated as first year radiology residents (R1s), giving them resident-level access to the Picture Archive and Communication System (PACS) and dictation software, and allowing them to perform entry-level procedures with appropriate supervision. After implementation of the elective, a 5-question online survey was sent to two hundred and ninety-eight PDs and APDs via the Association of Program Directors in Radiology (APDR) listserv, of which seventy-two responses were compiled, yielding a response rate of 24%. The survey focused on how a hands-on medical student elective would help in assessing prospective candidates and predicting R1 performance. Most respondents felt interest in radiology, motivation, and interpersonal skills would be better assessed after such an elective and the vast majority felt hands-on Advanced Elective would be at least slightly predictive of first year resident performance. Based on this information, we believe implementing a hands-on advanced radiology elective would significantly help address the passive nature of traditional radiology electives, providing valuable information to PDs and APDs and giving the best possible radiology experience to our medical students.

[Expression and clinical significance of plasma methylated SEPT 9 gene in patients with primary liver cancer].

Objective: To investigate the expression and clinical significance of plasma methylated SEPT9 (mSEPT9) gene in patients with primary liver cancer. Methods: 393 cases who visited our hospital from May 2016 to October 2018 were selected. Among them, 75 cases were in the primary liver cancer (PLC) group, 50 cases were in the liver cirrhosis (LC) group, and 268 cases were in the healthy control group (HC). The three groups' positive rates of mSEPT9 expression in the peripheral plasma were detected by the polymerase chain reaction (PCR) fluorescent probe method. The correlational clinical features of liver cancer were analyzed. At the same time, the electrochemiluminescence detection method was used to compare the AFP positive rate. Statistical analysis was conducted using chi-square tests or continuity-corrected chi-square tests. Results: 367 cases actually had valid samples. There were 64, 42, and 64 cases in the liver cancer group, cirrhosis group, and healthy control group, respectively. Among them, 34 cases of liver cancer were verified from pathological tissues. The positive rate of plasma mSEPT9 was significantly higher in the liver cancer group than that in the liver cirrhosis and healthy control groups [76.6% (49/64), 35.7% (15/42), and 3.8% (10/261), respectively], and the differences were statistically significant (χ (2) = 176.017, P < 0.001). The sensitivity of plasma mSEPT9 detection (76.6%) was significantly better in liver cancer (76.6%) than that of AFP patients (54.7%), and the difference was statistically significant (χ (2) = 6.788, P < 0.01). Compared with the single detection, the sensitivity and specificity of plasma mSEPT9 combined with AFP were significantly improved (89.7% vs. 96.3%, respectively). Patients with liver cancer aged≥50 years, with clinical stage II or above, and those with pathological signs of moderate to low differentiation had higher levels of plasma mSEPT9 positive expression, and the differences were statistically significant (χ (2) = 6.41, 9.279, 6.332, P < 0.05). During the follow-up period, the survival time of liver cancer patients with positive plasma mSEPT9 expression was significantly shorter than that of those with negative expression (310 ± 26 days vs. 487 ± 59 days, respectively), with statistically significant differences (Log Rank P = 0.039). Conclusion: In China, the positive rate of plasma mSEPT9 detection in liver cancer patients is higher than that of AFP in relation to age, clinical stage, and degree of tissue differentiation; additionally, it has certain survival predictive values. As a result, detecting this gene has important clinical significance and potential clinical application value in the non-invasive diagnosis and prognosis assessment of patients with primary liver cancer.

Sex difference in the expression of PD-1 of non-small cell lung cancer.

Evidence increasingly indicated that lung cancer incidence in female individuals continue to rise, and women have a higher risk to develop adenocarcinoma than men. Male and female individuals differ in their innate and adaptive immune responses, and there are sex differences in response to the PD-1/PD-L1-dependent blocking immunotherapy. Whether the differential expression of PD-1 between genders affect the response to blocking treatment is currently unknown. In this study, we examined sex differences in serum sPD-1, mPD-1 expression on T cells, and sex hormone levels in non-small cell lung cancer (NSCLC) patients. Our results revealed a higher level of sPD-1 and expression of PD-1 on CD4+T cell in female patients than in male patients; we identified that serum sPD-1 level and the expression of mPD-1 on T cells were significantly reduced in NSCLC; we also found that serum testosterone level increased in female patients compared with control subjects and that increased testosterone downregulated the expression of mPD-1 on T cell. These findings provide a better understanding of the differences in PD-1 expression between genders in NSCLC patients and the effect of sex hormones on PD-1 expression and supply evidence for early lung cancer diagnosis and responsiveness to immune checkpoint inhibitors.

[Factors analysis of worsening renal function in patients with acute right ventricular myocardial infarction during hospitalization].

Objective: To analyze the related factors of worsening renal function (WRF) in patients with acute right ventricular myocardial infarction (RVMI) during hospitalization. Methods: A total of 98 patients with acute RVMI admitted to the emergency comprehensive ward of Beijing Anzhen Hospital from August 2011 to January 2020 were enrolled in this cross-sectional study. According to the situation of WRF, the patients were divided into non-WRF group (76 cases) and WRF group (22 cases). WRF was defined as ≥0.3 mg/dL increase in serum creatinine level from baseline on day 6 of hospitalization (if hospital stay<6 days, it was at discharge). Baseline data, intravenous fluid infusion, diuretic and significant positive balance of patients' intake and output volume [any 24 h intakes and outputs ≥1 000 ml or any consecutive 72 h intakes and outputs ≥2 000 ml within 6 d of hospitalization (if hospitalization<6 d, it was from admission to discharge)] were obtained, and the differences of above indicators between the two groups were analyzed. Multiple logistic regression model was used to analyze the related factors of WRF. Results: The ages of patients in WRF group and non-WRF group were 60 (50, 68) and 63 (52, 72) years, and the male proportions were 63.6% (14 cases) and 76.3% (58 cases), respectively, and there was no significant difference (all P>0.05). The proportion of positive balance was 31.8% (7 cases) in WRF group, which was higher than 14.5% (11 cases) in non-WRF group (P=0.034). The rate of loop diuretic use in WRF group was 4.5% (1 case), lower than that in non-WRF group 10.5% (8 cases) (P=0.027). After adjusting for age, sex, baseline estimated glomerular filtration rate (eGFR), preoperative isoproterenol/temporary pacemaker/atropine use, significant positive balance of intake and output volume, and loop diuretic use, it was found that eGFR≥60 ml·min-1·1.73 m-2 and significant positive balance were associated with WRF, the OR (95%CI) were 0.71 (0.62-0.86) and 1.21 (1.02-1.43) (both P<0.05); After eliminating the variable of significant positive balance in the above model, loop diuretic use was found to be a correlation factor for WRF, with an OR (95%CI) of 0.89 (0.72-0.97) (P<0.05). Conclusions: Significant positive balance of intake and output volume during hospitalization in patients with acute RVMI is a risk factor for WRF on day 6 or at discharge. In the presence of a significant positive balance, loop diuretic use is a protective factor for WRF.

[Clinical phenotype analysis of 6 cases of TTC21B gene related nephronophthisis].

Objective: To analyze the clinical characteristics of 6 children with TTC21B-related nephronophthisis to provide reference for early clinical diagnosis. Methods: The general condition, clinical manifestations, laboratory tests and other clinical data of 6 children from 4 families diagnosed with nephronophthisis by genetic testing in Shanghai Children's Hospital from January 2015 to December 2020 were analyzed retrospectively. Results: A total of 6 children (3 males and 3 females) developed proteinuria and progressive renal dysfunction in early infancy. The onset age of proteinuria was 18 (6, 25) months. The age at the onset of renal impairment was 22 (10, 36) months. All 6 children progressed to end-stage renal disease (ESRD) within 10 (4, 65) months of onset. Five children had hypertension, 3 children with abnormal liver function, 2 children with visceral translocation and 1 child with growth retardation. The genetic results suggested that all children carried variations TTC21B gene p.C518R. Conclusions: Children with TTC21B gene p.C518R nephronophthisis had proteinuria and progressed to ESRD at the early stage of life. These nephronophthisis patients commonly presented with liver and renal dysfunction.

[Analysis of differences and influencing factors of liver injury associated with different strains of 2019-nCoV infection].

Objective: To analyze whether there are differences and related influencing factors in liver injury associated with different strains of 2019-nCoV/SARS-CoV-2 infection. Methods: Data of epidemiology, clinical symptoms, laboratory tests, and treatment outcomes of patients with COVID-19 infection confirmed with Alpha and Delta virus strain in Zhejiang Province were retrospectively collected. Statistical analysis was performed using independent samples t-test or Mann-Whitney U test, χ2 test or Fisher's exact test, and logistic regression analysis. Results: A total of 788 and 381 cases with Alpha and Delta virus strain were included. Vaccination ratio was 0% in Alpha and 85.30% in Delta group (P<0.001), The proportion of patients with fever (80.71% vs. 40.94%, P<0.001) was significantly higher in Alpha than Delta strain group. The proportion of critical ill patients was significantly higher in Delta group (9.90% vs. 1.57%, respectively, P<0.001). The virus negative conversion time was significantly longer in Delta than Alpha group (22 d vs. 11 d, P<0.001), but the incidence of liver injury was significantly higher in Alpha than Delta group (20.05% vs. 13.91%, P=0.011). Univariate analysis showed that Alpha virus strain infection, male sex, body mass index, chronic liver disease, fever, diarrhea, shortness of breath, severe/critical illness, elevated creatine kinase (CK), elevated international normalized ratio (INR) and an elevated neutrophil/lymphocyte ratio was significantly associated with an increased risk of liver injury occurrence, and in patients with pharyngeal pain the risk of liver injury occurrence was significantly reduced. Multivariate analysis showed that shortness of breath [OR, 2.667 (CI: 1.389-5.122); P=0.003], increased CK [OR, 2.544 (CI: 1.414-4.576); P=0.002] and increased INR [OR, 1.721] (CI: 1.074-2.758); P=0.024] was significantly associated with an increased risk of liver injury occurrence, and in patients with pharyngeal pain the risk of liver injury occurrence was significantly reduced [OR, 0.424 (CI: 0.254-0.709); P=0.001]. Conclusion: Although the virulence of the Delta is stronger than Alpha strain, most patients infected with Delta strain vaccinated against COVID-19 in Zhejiang province had milder clinical symptoms and a lower incidence and degree of liver injury. Notably, the infection risk even remains after vaccination; however, symptoms and the incidence of severe and critical illness can be significantly reduced.

Measuring health consumers' engagement at the governance level: development and validation of the Middlemore Consumer Engagement Questionnaire.

AIM: To develop and validate a questionnaire to measure health CE at governance level. METHOD: This study used qualitative and quantitative methods (including focus groups, cognitive interviews and an international survey), and consisted of two phases. In Phase 1, an initial list of items was generated and refined with feedback from health consumer representatives. In Phase 2, a draft survey was distributed to n=227 consumers from New Zealand, Australia and Canada. The benefit and relevance of using the questionnaire was explored through face-to-face interviews with five CE leaders from New Zealand healthcare organisations. RESULTS: The proposed questionnaire comprises 25 statements relating to CE. Respondents indicate their level of agreement with the statements on a five-point Likert-type scale. Focus group and cognitive interview participants found the questionnaire relevant and easy to understand. The questionnaire scores correlated with the PPEET, another instrument measuring consumer engagement, and showed excellent internal consistency (Cronbach's alpha=0.97), unidimensionality and test-retest reliability (r=0.84). CONCLUSION: The proposed questionnaire measures CE at governance level and can be used for international comparisons and benchmarking. It showed sound psychometric properties and its value and relevance was recognised by health consumer representatives and leaders with CE roles in New Zealand healthcare organisations.

Peer learning in emergency radiology: effects on learning, error identification, and radiologist experience.

PURPOSE: We established and evaluated a peer learning program in an emergency radiology (ER) division. Peer learning is an alternative to peer review focusing on non-punitive error reporting to mitigate consequences of inevitable human error. The central component is the peer learning conference, where cases are presented, key teaching points are discussed, and process improvement ideas are solicited. METHODS: We established a prior imaging-based case identification system and a bimonthly remote videoconference where ER faculty discuss 5-15 cases selected for learning or process improvement opportunities. Case identification and conference characteristics were captured. A survey focused on learning and performance outcomes was administered to faculty initially and showed improved scores after 6 months. RESULTS: Cases selected for conference favored perception errors (46%), with great calls (17%) and process improvement (15%) the next most common categories. A variety of anatomical regions were represented, with abdominal (35%) and musculoskeletal (29%) most common. Error detection was improved over peer review. All participants find the system easy to use and prefer peer learning to peer review for learning and process improvement. CONCLUSION: A peer learning program can be successfully implemented within a busy academic emergency radiology division, as evidenced by increasing buy-in and engagement scores over time. When tied to a departmental peer learning infrastructure, interdisciplinary expertise and robust case identification can be leveraged to increase learning opportunities.

Traumatic Intracranial Hemorrhage on CT After Ground-Level Fall in Adult Patients Receiving Antithrombotic Therapy: A Retrospective Case-Control Study.

BACKGROUND. Antithrombotic medications may increase the risk and severity of traumatic intracranial hemorrhage (tICH) after minor head trauma. OBJECTIVE. The purpose of this study was to determine the frequency, distribution, and clinical course of tICH in patients receiving antithrombotic therapy who present with good neurologic status after a ground-level fall. METHODS. This retrospective study included 1630 patients (693 women and 937 men; mean age, 80.2 ± 12.7 [SD] years) who underwent head CT after presenting to the emergency department after a ground-level fall between January 1 and December 31, 2020; all patients had a Glasgow Coma Scale score of 14 or higher and no focal neurologic deficit. Patients with tICH were identified on the basis of clinical reports. In patients with tICH, images from initial head CT examinations were reviewed for characteristics of tICH, images from follow-up head CT examinations (performed within 24 hours) were reviewed for hematoma expansion, and clinical outcomes were extracted from medical records. Patients receiving antithrombotic therapy and control patients (those not receiving antithrombotic therapy) were compared. RESULTS. The antithrombotic therapy group included 954 patients (608 receiving anticoagulant therapy; 226, antiplatelet therapy; and 120, both therapies); the control group included 676 patients. A total of 63 patients (3.9%; 95% CI, 2.9-4.8%) had tICH. The antithrombotic therapy and control groups were not significantly different in terms of the frequency of tICH (4.4% vs 3.1%, p = .24), midline shift (10.0% vs 7.1%, p = .76) or regional mass effect (33.3% vs 14.3%, p = .19) on initial CT. Hematoma expansion on follow-up CT occurred in 11 of 42 patients (26.2%) in the antithrombotic group and one of 21 patients (4.8%) in the control group (p = .04). Two patients required neurosurgical intervention, and three deaths related to tICH occurred within 30 days; all five of these patients were receiving antithrombotic therapy. CONCLUSION. Antithrombotic therapy use was not associated with an increased frequency of tICH, although it was associated with an increased frequency of hematoma expansion at follow-up. CLINICAL IMPACT. In patients with good neurologic status after a ground-level fall, the findings suggest application of a similar strategy for selecting patients for initial head CT, regardless of antithrombotic therapy use; if initial head CT shows tICH, early follow-up head CT should be systematically performed in those receiving antithrombotic therapy, though it possibly should be deferred in other patients.

[Safety and efficacy of left atrial appendage closure combined with patent foramen ovale closure for atrial fibrillation patients with patent foramen ovale].

Objective: To analyze the safety and efficacy of combined left atrial appendage (LAA) and patent foramen ovale (PFO) closure in adult atrial fibrillation (AF) patients complicating with PFO. Methods: This study is a retrospective and cross-sectional study. Seven patients with AF complicated with PFO diagnosed by transesophageal echocardiography (TEE) in Zhoupu Hospital Affiliated to Shanghai University of Medicine & Health Sciences from June 2017 to October 2020 were selected. Basic data such as age, gender and medical history were collected. The atrial septal defect or PFO occluder and LAA occluder were selected according to the size of PFO, the ostia width and depth of LAA. Four patients underwent left atrial appendage closure(LAAC) and PFO closure at the same time. PFO closure was performed during a one-stop procedure of cryoablation combined with LAAC in 2 patients. One patient underwent PFO closure at 10 weeks after one-stop procedure because of recurrent transient ischemic attack (TIA). All patients continued to take oral anticoagulants. TEE was repeated 8-12 weeks after intervention. In case of device related thrombus(DRT), TEE shall be rechecked 6 months after adjusting anticoagulant and antiplatelet drug treatment. Patients were follow-up at 1, 3, 6, 12, 24 months by telephone call, and the occurrence of cardio-cerebrovascular events was recorded. Results: Among the 7 patients with AF, 2 were male, aged (68.0±9.4) years, and 3 had a history of recurrent cerebral infarction and TIA. Average PFO diameter was (3.5±0.8)mm. Three patients were implanted with Watchman LAA occluder (30, 30, 33 mm) and atrial septal defect occluder (8, 9, 16 mm). 2 patients were implanted with LAmbre LAA occluder (34/38, 18/32 mm) and PFO occluder (PF1825, PF2525). 2 patients were implanted with LACbes LAA occluder (24, 28 mm) and PFO occluder (PF2525, PF1825) respectively. The patients were followed up for 12 (11, 24) months after operation. TEE reexamination showed that the position of LAA occluder and atrial septal defect occluder or PFO occluder was normal in all patients. DRT was detected in 1 patient, and anticoagulant therapy was adjusted in this patient. 6 months later, TEE showed that DRT disappeared. No cardiovascular and cerebrovascular events occurred in all patients with AF during follow-up. Conclusions: In AF patients complicated with PFO, LAAC combined with PFO closure may have good safety and effectiveness.

[Application of bionics in spinal surgery].

Spinal bionic therapy is the application of bionics concept, by imitating the natural anatomical structure and physiological function of the spine, to treat spinal diseases using various modern technology, materials and equipment .How to repair or preserve the anatomical structure and function of spine to the maximum extent while treating spinal diseases is an important content of spinal bionic therapy.Firstly, the use of movable spinal implants not only preserves the spinal mobility function to a certain extent, reduces the degeneration of adjacent segments, but also reduces the incidence of internal fixation fracture and improves the long-term efficacy.Secondly, with the help of the development of three dimensional printing technology, personalized artificial prostheses can be made to fill the spinal structure with complex defects, and biological scaffolds and functional prostheses with anti-tumor drugs can not only realize the biomimetic and functional spine anatomy, but also become a multiplier of the efficacy of anti-tumor drugs.Thirdly, in the design and manufacture of spinal orthopaedic braces, computer aided design and manufacturing technology can make spinal orthopaedic braces more comfortable with better orthopaedic effect and ergonomic characteristics.How to apply bionics concepts and relate technologies to spinal surgery have not been determined yet, and no relevant diagnosis and treatment guidelines have been formulated.It is foreseeable that with the continuous development of medical technology, the content of spinal bionic therapy will be gradually enriched and improved, and become a powerful measure to overcome difficulties in the diagnosis and treatment of spinal surgery diseases.

BiTE secretion from in situ-programmed myeloid cells results in tumor-retained pharmacology.

Bispecific T-Cell Engagers (BiTEs) are effective at inducing remission in hematologic cancers, but their use in solid tumors has been challenging due to their extreme potency and on-target, off-tumor toxicities in healthy tissue. Their deployment against solid tumors is further complicated by insufficient drug penetration, a hostile tumor microenvironment, and immune escape. To address these challenges, we developed targeted nanocarriers that can deliver in vitro-transcribed mRNA encoding BiTEs to host myeloid cells - a cell type that is actively recruited into the tumor microenvironment. We demonstrate in an immunocompetent mouse model of ovarian cancer, that infusion of these nanoparticles directs BiTE expression to tumor sites, which reshapes the microenvironment from suppressive to permissive and triggers disease regression without systemic toxicity. In contrast, conventional injections of recombinant BiTE protein at doses required to achieve anti-tumor activity, induced systemic inflammatory responses and severe tissue damage in all treated animals. Implemented in the clinic, this in situ gene therapy could enable physicians - with a single therapeutic - to safely target tumor antigen that would otherwise not be druggable due to the risks of on-target toxicity and, at the same time, reset the tumor milieu to boost key mediators of antitumor immune responses.

[Clinical application value of peripheral blood metagenomic next-generation sequencing test for patients with hematological diseases accompanied by fever].

Objective: To investigate the clinical application value of peripheral blood metagenomic next-generation sequencing (mNGS) test for patients with hematological diseases accompanied by fever. Methods: The blood mNGS results and clinical data of inpatients with hematological diseases accompanied by fever treated in the Hematology Department of Tianjin Medical University General Hospital in March 2020 to June 2021were retrospectively analyzed. A total of 90 patients with 98 cases of specimens were included. The pathogen distribution characteristics and mNGS test performance were analyzed. Results: The positive rate of peripheral blood mNGS was significantly higher than that of traditional examination (68.37% vs 37.76%, P<0.001) and blood culture (68.37% vs 9.18%, P<0.001) . Viral, bacterial, and fungal infections accounted for 38.81%, 14.93%, and 2.99% in patients with single-pathogen infections, respectively. Polymicrobial infections accounted for 43.28%, in which viral and bacterial coinfections were the most common type (25.37%) . There were 55 virus-positive cases (82.09%) , 30 bacteria-positive cases (44.78%) , and 14 fungus-positive cases (20.90%) . The clinical approval rate of peripheral blood mNGS was 64.63% (63/98) . The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of peripheral blood mNGS were 75.68%, 36.07%, 41.79%, and 70.97%, respectively, and the overall consistency rate with traditional examination was 51.02%. Of the 22 pulmonary infection cases with no detectable pathogens by conventional tests, the pathogens were identified by peripheral blood mNGS in 14 cases, 10 of which were clinically approved. Conclusion: The positive rate of peripheral blood mNGS was significantly higher than that of blood culture and traditional laboratory examination. Peripheral blood mNGS had a high clinical recognition rate, sensitivity, and NPV in the detection of pathogens in patients with hematological diseases accompanied by fever.