Polymer colloidal motors with photodynamic-regulated propulsion.

Artificial colloidal motors capable of converting various external energy into mechanical motion, have emerged as attractive photosensitizer (PS) nanocarriers with good deliverability for photodynamic therapy. However, photoactivated 3O2-to-1O2 transformation as the most crucial energy transfer of the photodynamic process itself is still challenging to convert into autonomous transport. Herein, we report on PS-loaded thiophane-containing semiconducting conjugated polymer (SCP)-based polymer colloidal motors with asymmetric geometry for photodynamic-regulated propulsion in the liquid. The asymmetrical presence of the SCP phases within the colloidal motors would lead to significant differences in the 3O2-to-1O2 transformation and 1O2 release manners between asymmetrical polymer phases, spontaneously creating asymmetrical osmotic pressure gradients across the nanoparticles for powering the self-propelled motion under photodynamic regulation. This photoactivated energy-converting behavior can be also combined with the photothermal conversion of the SCP phases to create two energy gradients exerting diffusiophoretic/thermophoretic force on the colloidal motors for achieving multimode synergistic propulsion. This unique motile feature endows the light-driven PS nanocarriers with good permeability against various physiological barriers in the tumor microenvironment for enhancing antitumor efficacy, showing great potential in phototherapy.

Characteristics of surface ozone pollution and its correlations with meteorological factors: the case of Xiangtan.

Based on ozone (O3) monitoring data for Xiangtan and meteorological observation data for 2020-2022, we examined ozone pollution characteristics and the effects of meteorological factors on daily maximum 8-h average ozone (O3-8h) concentrations in Xiangtan. Thus, we observed significant increases as well as notable seasonal variations in O3-8h concentrations in Xiangtan during the period considered. The ozone and temperature change response slope (KO3-T) indicated that local emissions had no significant effect on O3-8h generation. Further, average O3-8h concentration and maximum temperature (Tmax) values showed a polynomial distribution. Specifically, at Tmax < 27 °C, it increased almost linearly with increasing temperature, and at Tmax between 27 and 37 °C, it showed an upward curvilinear trend as temperature increased, but at a much lower rate. Then, at Tmax > 37 °C, it decreased with increasing temperature. With respect to relative humidity (RH), the average O3-8h concentration primarily exceeded the standard value when RH varied in the range of 45-65%, which is the key humidity range for O3 pollution, and the inflection point for the correlation curve between O3-8h concentration and RH appeared at ~55%. Furthermore, at wind speeds (WSs) below 1.5 m∙s-1, O3-8h concentration increased rapidly, and at WSs in the 1.5-2 m∙s-1 range, it increased at a much faster rate. However, at WSs > 2 m∙s-1, it decreased slowly with increasing WS. O3-8h concentration also showed the tendency to exceed the standard value when the dominant wind directions in Xiangtan were easterly or southeasterly.

Value of a nomogram model in early recurrence of pancreatic ductal adenocarcinoma after laparoscopic pancreaticoduodenectomy / 临床肝胆病杂志

ObjectiveTo investigate the risk factors for early tumor recurrence after laparoscopic pancreaticoduodenectomy （LPD） in patients with pancreatic ductal adenocarcinoma （PDAC）， and to establish a predictive model. MethodsA retrospective analysis was performed for the clinical data of 240 PDAC patients who underwent LPD in The First Hospital of Jilin University from April 2016 to July 2022， with early postoperative tumor recurrence （time to recurrence ≤12 months） as the study outcome. The patients were randomly divided into training group with 168 patients and validation group with 72 patients at a ratio of 7∶3. In the training group， there were 70 patients （41.67%） with early postoperative recurrence and 98 （58.33%） without early recurrence， and in the validation group， there were 32 （44.44%） with early postoperative recurrence and 40 （55.56%） without early recurrence. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； a logistic regression analysis was used to investigate the risk factors for early postoperative recurrence； the receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to evaluate the discriminatory ability of the model， with AUC>0.75 indicating that the model had adequate discriminatory ability. The Bootstrap resampling method was used for validation after 1 000 times of random sampling， and the model was validated again in the validation group. The calibration curve and the Hosmer-Lemeshow goodness-of-fit test were used to evaluate the degree of calibration， and the decision curve analysis was used to evaluate clinical practicability. ResultsThe univariate and multivariate analyses showed that preoperative CA19-9 level≥37 U/mL （odds ratio ［OR］=6.265， 95% confidence interval ［CI］： 1.938‍ ‍—‍ ‍20.249， P<0.05）， maximum tumor diameter >3 cm （OR=10.878， 95%CI： 4.090‍ ‍—‍ ‍28.932， P<0.05）， poor tumor differentiation （OR=3.679， 95%CI： 1.435‍ ‍—‍ ‍9.433， P<0.05）， lymph node metastasis （OR=0.209， 95%CI： 0.080‍ ‍—‍ ‍0.551， P<0.05）， and absence of adjuvant chemotherapy after surgery （OR=0.167， 95%CI： 0.058‍ ‍—‍ ‍0.480， P<0.05）. A nomogram model was constructed based on these factors； the ROC curve analysis showed that the model had an AUC of 0.895 （95%CI： 0.846‍ ‍—‍ ‍0.943， P<0.001）， and the calibration curve and the Hosmer-Lemeshow test showed that the model had a good degree of calibration （P=0.173）. The decision curve analysis showed that the nomogram had a good clinical application value. ConclusionPreoperative CA19-9 level ≥37 U/mL， maximum tumor diameter >3 cm， poor tumor differentiation， lymph node metastasis， and absence of adjuvant chemotherapy after surgery are independent risk factors for the early recurrence of PDAC after LPD， and the nomogram model established based on these factors can effectively predict early postoperative recurrence.

Quality evaluation of Chinese and global guidelines/consensus for TDM of anti-TNF-α agents in patients with inflammatory bowel disease / 中国药房

OBJECTIVE To evaluate the quality of guidelines/consensus on therapeutic drug monitoring （TDM） of anti-tumor necrosis factor-α （TNF-α） in patients with inflammatory bowel disease （IBD） in China and globally. METHODS PubMed， Embase， CNKI， Wanfang data， VIP， and release websites of guidelines/consensus in China and globally were searched to collect guidelines/expert consensus on TDM with anti-TNF-α for IBD patients. The search period was from database establishment to June 2023. After two investigators independently screened the literature and extracted the data， the methodological quality of the included guidelines/consensuses was evaluated using the Appraisal of Guidelines for Research and Evaluation Ⅱ. The main recommendations of the included guidelines/consensuses were summarized. RESULTS A total of 9 articles were included， 3 were guidelines and 6 were expert consensus. The standardized percentages of the 9 guidelines/consensus in the 6 dimensions （scope and aims， participants， rigor of formulation， clarity of expression， application， and editorial independence） were 90.43%， 41.98%， 52.55%， 85.49%， 19.00%， and 76.85%， respectively. Eight guidelines/consensus had a recommendation of grade B and one consensus of grade C. The main recommendations involve TDM application scenarios， threshold ranges， strategy adjustments， detection methods， and interpretation of results. Most guidelines/consensus recommend passive TDM for non-responders. It is recommended to set the TDM concentration range according to the expected treatment results and make strategy adjustments in combination with the disease condition and TDM results. Additionally， the same test method is recommended for the same patient. Some guidelines/consensus hold that no differences were noted in the interpretation of results between biosimilar and original drug. CONCLUSIONS The overall quality of the included guidelines/consensus was fair， with relatively consistent recommendation. Clinicians need to understand the characteristics and limitations of TDM with this class of drugs， and interpret and apply results of TDM in combination with specific clinical treatment goals.

Tanshinone⠡A inhibits excessive autophagy and protects myocardium against ischemia/reperfusion injury via 14-3-3η/Akt/Beclin1 pathway.

Excessive autophagy induced by reperfusion is one of the causes of severe myocardial injury. Tanshinone IIA (TSN) protects the myocardium against ischemia/reperfusion (I/R) injury. The mechanism by which the inhibition of excessive autophagy contributes to the myocardial protection by TSN is unclear. The protective effects and mechanisms of TSN were studied in H9c2 cells and rats after anoxia/reoxygenation (A/R)-or I/R-induced myocardial injury. The results showed that after the injury, cell viability decreased, lactate dehydrogenase and caspase 3 activity and apoptosis increased, and autophagy was excessively activated. Further, redox imbalance and energy stress, mitochondrial dysfunction, reduced myocardial function, increased infarct area, and severely damaged morphology were observed in rats. TSN increased 14-3-3η expression and regulated Akt/Beclin1 pathway, inhibited excessive autophagy, and significantly reversed the functional, enzymological and morphological indexes in vivo and in vitro. However, the protective effects of TSN were mimicked by 3-methyladenine (an autophagy inhibitor) and were attenuated by pAD/14-3-3η-shRNA, API-2 (an Akt inhibitor), and rapamycin (an autophagy activator). In conclusion, TSN could increase 14-3-3η expression and regulate Akt/Beclin1 pathway, inhibit excessive autophagy, maintain the mitochondrial function, improve energy supply and redox equilibrium, alleviate apoptosis, and ultimately protect myocardium against I/R injury.

Engineered Organic Nanorockets with Light-Driven Ultrafast Transportability for Antitumor Therapy.

Nanomedicines confront various complicated physiological barriers limiting the accumulation and deep penetration in the tumor microenvironment, which seriously restricts the efficacy of antitumor therapy. Self-propelled nanocarriers assembled with kinetic engines can translate external energy into orientated motion for tumor penetration. However, achieving a stable ultrafast permeability at the tumor site remains challenging. Here, sub-200 nm photoactivated completely organic nanorockets (NRs), with asymmetric geometry conveniently assembled from photothermal semiconducting polymer payload and thermo-driven macromolecular propulsion through a straightforward nanoprecipitation process, are presented. The artificial NRs can be remotely manipulated by 808 nm near-infrared light to trigger the photothermal conversion and Curtius rearrangement reaction within the particles for robustly pushing nitrogen out into the solution. Such a two-stage light-to-heat-to-chemical energy transition effectively powers the NRs for an ultrafast (≈300 µm s-1 ) and chemical medium-independent self-propulsion in the liquid media. That endows the NRs with high permeability against physiological barriers in the tumor microenvironment to directionally deliver therapeutic agents to target lesions for elevating tumor accumulation, deep penetration, and cellular uptake, resulting in a significant enhancement of antitumor efficacy. This work will inspire the design of advanced kinetic systems for powering intelligent nanomachines in biomedical applications.

Luteoloside pretreatment attenuates anoxia-induced damage in cardiomyocytes by regulating autophagy mediated by 14-3-3η and the AMPKα-mTOR/ULK1 pathway.

The relation between ischemia and heart failure is well demonstrated, and several studies suggested that realizing the physiological role of autophagy will be of great importance. Luteoloside (Lut) is one of the main components of Lonicera japonica flos and exhibits antioxidant, anti-inflammatory, and cardioprotective properties. To determine if Lut pretreatment enhanced autophagy by 14-3-3η expression and the AMPKα-mTOR/ULK1 pathway and protected the neonatal rat cardiomyocytes (NRCMs) against anoxia damage, NRCMs were treated using 20 µM Lut for 36 h, and the anoxia damage model was established using NRCMs. The indexes reflecting the condition of NRCMs, oxidative stress level, and mitochondrial function were evaluated. In addition, the expression and phosphorylation of 14-3-3η and AMPKα/mTOR/ULK1, and autophagy markers (LC3II, P62) and the abundance of autophagy lysosomes were detected. Results revealed that Lut pretreatment alleviated anoxia- induced damage in NRCMs, that is, Lut pretreatment could increase cell viability, decrease LDH activity and apoptosis, suppressed ROS generation and oxidative stress, restored intracellular ATP levels, stabilized MMP levels, and inhibited mPTP opening. Furthermore, Lut pretreatment could enhance autophagy via upregulating 14-3-3η, LC3II expression and increasing p-AMPKα/AMPKα and p-ULK1/ULK1 level, whereas P62 expression and p-mTOR/mTOR level decreased; the fluorescence intensity of autolysosomes also increased. However, in the NRCMs treated with pAD/14-3-3η RNAi or incubated with 3-MA (an autophagy inhibitor), the abovementioned effects of Lut pretreatment were reduced. Taken together, Lut pretreatment could enhance autophagy by upregulating 14-3-3η expression to influence the AMPKα-mTOR/ ULK1 pathway against anoxia-induced damage in NRCMs.

Reinforced radiculoplasty for the treatment of symptomatic sacral Tarlov cysts: A clinical analysis of 71 cases / 北京大学学报(医学版)

OBJECTIVE@#To investigate the safety and efficacy of reinforced radiculoplasty in the treatment of symptomatic sacral Tarlov cysts (TCs).@*METHODS@#A retrospective analysis was performed on the clinical data and follow-up data of 71 patients with symptomatic sacral TCs who underwent reinforced radiculoplasty in the Neurosurgery Department of Peking University Third Hospital from June 2018 to March 2021. All the operations were performed under neuroelectrophysiological monitoring. Intraoperative cyst exploration, partial resection of the cyst wall, narrowing of the leak, nerve root sleeve radiculoplasty and artificial dural reinforcement were performed. The incidence of postoperative complications and new neurological dysfunction was analyzed. Visual analogue scale (VAS) was used to assess the changes of pain before and after surgery. The Japanese Orthopedics Association (JOA) low back pain score was used to evaluate the changes in nerve function before and after surgery.@*RESULTS@#In the study, 71 patients had 101 TCs, 19 (18.8%) TCs originated from the left S1 nerve, 26 (25.7%) originated from the left S2 nerve, 3 (3.0%) originated from the left S3 nerve, 14 (13.9%) originated from the right S1 nerve, 33 (32.7%) originated from the right S2 nerve, 6 (5.9%) originated from the right S3 nerve, all the TCs underwent reinforced radiculoplasty. Deep infection (1 case), subcutaneous effusion (1 case), fat li-quefaction (1 case) and urinary tract infection (4 cases) were recorded postoperatively. The patients were followed up for 12-43 months (median, 26 months). Two cases had new urinary retention after operation, and the catheter was removed at the end of the first and second months respectively. One case had new fecal weakness, which improved after 3 months. Compared with preoperation, VAS decreased significantly at the last follow-up [median, 6 (4-9) vs. 1 (0-5), Z=-7.272, P < 0.001], JOA score increased significantly [median, 20 (16-25) vs. 27 (18-29), Z=-7.265, P < 0.001]. There were 18 cured cases (25.4%), 41 excellent cases (57.7%), 8 effective cases (11.3%), and 4 invalid cases (5.6%). The total efficiency was 94.4% (67/71). Two (1.98%) cysts recurred.@*CONCLUSION@#For patients with symptomatic sacral TCs, reinforced radiculoplasty can significantly improve the pain and nerve function, which is safe and reliable.

Research progress in transcriptional and immunological biomarkers associated with tuberculosis infection / 中华预防医学杂志

Tuberculosis (TB) is an infectious disease that poses a serious threat to human health. About a quarter of the world's population were infected with Mycobacterium tuberculosis in 2020, and the majority of them were latently infected. Approximately 5%-10% of the population with latent tuberculosis infection may progress to active TB disease. Identifying latent TB infection from active TB by biomarkers and screening people with latent TB infection at high risk of progression for preventive treatment by biomarkers that can reliably predict the progression is one of the most effective strategies to control TB. This article reviews the progress of research on transcriptional and immunological biomarkers for identifying TB infection and predicting the progression from latent infection to active TB, with the aim of providing new ideas for tuberculosis control.

Puerarin activates adaptive autophagy and protects the myocardium against doxorubicin-induced cardiotoxicity via the 14-3-3γ/PKCε pathway.

Doxorubicin (Dox)-induced cardiotoxicity (DIC) seriously threatens the health of related patients. Studies have confirmed that 14-3-3γ and protein kinase C epsilon (PKCε) are the endogenous protective proteins. Puerarin (Pue) is a bioactive ingredient isolated from the root of Pueraria lobata. It possesses many pharmacological properties, which have been widely used in treating and adjuvant therapy of cardiovascular diseases. In the study, we intended to explore the effects and mechanism of Pue pretreatment to protect the myocardium against DIC injury. Adult mice and H9c2 cells were pretreated with Pue, and the injury model was made with Dox. Results showed that Pue pretreatment alleviated DIC injury, as revealed by increased cell viability, decreased LDH activity and apoptosis, inhibited excess oxidative stress, maintained mitochondrial function and energy metabolism, and improved myocardial function. Furthermore, Pue pretreatment upregulated 14-3-3γ expression, interacted with PKCε, phosphorylated and impelled migration to mitochondria, activated adaptive autophagy, and protected the myocardium. However, pAD/14-3-3γ-shRNA or εV1-2 (a PKCε activity inhibitor) or 3-methyladenine (an autophagy inhibitor) could weaken the above effects of Pue pretreatment. Together, Pue pretreatment could activate adaptive autophagy by the 14-3-3γ/PKCε pathway and protect the myocardium against DIC injury.

Photoactivated Organic Nanomachines for Programmable Enhancement of Antitumor Efficacy.

Limited permeability in solid tumors significantly restricts the anticancer efficacy of nanomedicines. Light-driven nanomotors powered by photothermal converting engines are appealing carriers for directional drug delivery and simultaneous phototherapy. Nowadays, it is still a great challenge to construct metal-free photothermal nanomotors for a programmable anticancer treatment. Herein, one kind of photoactivated organic nanomachines is reported with asymmetric geometry assembled by light-to-heat converting semiconducting polymer engine and macromolecular anticancer payload through a straightforward nanoprecipitation process. The NIR-fueled polymer engine can be remotely controlled to power the nanomachines for light-driven thermophoresis in the liquid media and simultaneously thermal ablating the cancer cells. The great manipulability of the nanomachines allows for programming of their self-propulsion in the tumor microenvironment for effectively improving cellular uptake and tumor penetration of the anticancer payload. Taking the benefit from this behavior, a programmed treatment process is established at a low drug dose and a low photothermal temperature for significantly enhancing the antitumor efficacy.

Symptom Persistence Despite Improvement in Cardiopulmonary Health - Insights from longitudinal CMR, CPET and lung function testing post-COVID-19

BackgroundThe longitudinal trajectories of cardiopulmonary abnormalities and symptoms following infection with coronavirus disease (COVID-19) are unclear. We sought to describe their natural history in previously hospitalised patients, compare this with controls, and assess the relationship between symptoms and cardiopulmonary impairment at 6 months post-COVID-19. MethodsFifty-eight patients and thirty matched controls underwent symptom-questionnaires, cardiac and lung magnetic resonance imaging (CMR), cardiopulmonary exercise test (CPET), and spirometry at 3 months following COVID-19. Of them, forty-six patients returned for follow-up assessments at 6 months. FindingsAt 2-3 months, 83% of patients had at least one cardiopulmonary symptom versus 33% of controls. Patients and controls had comparable biventricular volumes and function. Native cardiac T1 (marker of inflammation) and late gadolinium enhancement (LGE, marker of focal fibrosis) were increased in patients. Sixty percent of patients had lung parenchymal abnormalities on CMR and 55% had reduced peak oxygen consumption (pVO2) on CPET. By 6 months, 53% of patients remained symptomatic. On CMR, indexed right ventricular (RV) end-diastolic volume (-4{middle dot}3 mls/m2, P=0{middle dot}005) decreased and RV ejection fraction (+3{middle dot}2%, P=0{middle dot}0003) increased. Native T1 and LGE improved and was comparable to controls. Lung parenchymal abnormalities and peak VO2, although better, were abnormal in patients versus controls. 31% had reduced pVO2 secondary to fatigue and submaximal tests. Cardiopulmonary symptoms in patients did not associate with CMR, lung function, or CPET measures. InterpretationIn patients, cardiopulmonary abnormalities improve over time, though some measures remain abnormal relative to controls. Persistent symptoms at 6 months post-COVID-19 did not associate with objective measures of cardiopulmonary health. FundingNIHR Oxford and Oxford Health BRC, Oxford BHF CRE, UKRI and Wellcome Trust.

Analysis of Heart-Sound Characteristics during Motion Based on a Graphic Representation.

In this paper, the graphic representation method is used to study the multiple characteristics of heart sounds from a resting state to a state of motion based on single- and four-channel heart-sound signals. Based on the concept of integration, we explore the representation method of heart sound and blood pressure during motion. To develop a single- and four-channel heart-sound collector, we propose new concepts such as a sound-direction vector of heart sound, a motion-response curve of heart sound, the difference value, and a state-change-trend diagram. Based on the acoustic principle, the reasons for the differences between multiple-channel heart-sound signals are analyzed. Through a comparative analysis of four-channel motion and resting-heart sounds, from a resting state to a state of motion, the maximum and minimum similarity distances in the corresponding state-change-trend graphs were found to be 0.0038 and 0.0006, respectively. In addition, we provide several characteristic parameters that are both sensitive (such as heart sound amplitude, blood pressure, systolic duration, and diastolic duration) and insensitive (such as sound-direction vector, state-change-trend diagram, and difference value) to motion, thus providing a new technique for the diverse analysis of heart sounds in motion.

Minimally invasive treatment of cervical1-2 epidural neurilemmoma / 北京大学学报(医学版)

OBJECTIVE@#To explore the minimally invasive surgical method for cervical1-2 epidural neurilemmoma.@*METHODS@#The clinical features, imaging characteristics and surgical methods of 63 cases of cervical1-2 epidural neurilemmoma from July 2010 to December 2018 were reviewed and analyzed. Pain and numbness in occipitocervical region were the common clinical symptoms. There were 58 cases with pain, 30 cases with numbness, 3 cases with limb weakness and 2 cases with asymptomatic mass. Magnetic resonance imaging (MRI) showed that the tumors located in the cervical1-2 epidural space with diameter of 1-3 cm. The equal or slightly lower T1 and equal or slightly higher T2 signals were found on MRI. The tumors had obvious enhancement. Individualized laminotomy was performed according to the location and size of the tumors, and axis spinous processes were preserved as far as possible. Resection of tumor was performed strictly within the capsule.@*RESULTS@#Total and subtotal resection of tumor were achieved in 60 and 3 cases respectively, and no vertebral artery injury was found. The operation time ranged from 60 to 180 minutes, with an average of 92.83 minutes. The hospitalization time ranged from 3 to 9 days, with an average of 5.97 days. All tumors were confirmed as neurilemmoma by pathology. There was no postoperative infection or cerebrospinal fluid leakage. There was no new-onset dysfunction except 9 cases of numbness in the nerve innervation area. The period of follow-up ranged from 6 months to 8 years (median: 3 years). All the new-onset dysfunction recovered completely. Pain disappeared in all of the 58 patients with pain. Numbness recovered completely in 27 patients while slight numbness remained in another 3 patients. Three patients with muscle weakness recovered completely. The spinal function of all the patients restored to McCormick grade Ⅰ. No recurrence was found on MRI. No cervical spine instability or deformity was found on X-rays.@*CONCLUSION@#It is feasible to resect cervical1-2 epidural neurilemmoma by full use of the anatomical space between atlas and axis and individual laminotomy. It is helpful to prevent cervical instability or deformity by minimizing the destruction of cervical2 bone and preserving normal muscle attachment to cervical2 spinous process. Strict intracapsular resection can effectively prevent vertebral artery injury.

Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge

BackgroundThe medium-term effects of Coronavirus disease (COVID-19) on multiple organ health, exercise capacity, cognition, quality of life and mental health are poorly understood. MethodsFifty-eight COVID-19 patients post-hospital discharge and 30 comorbidity-matched controls were prospectively enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments. FindingsAt 2-3 months from disease-onset, 64% of patients experienced persistent breathlessness and 55% complained of significant fatigue. On MRI, tissue signal abnormalities were seen in the lungs (60%), heart (26%), liver (10%) and kidneys (29%) of patients. COVID-19 patients also exhibited tissue changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domain relative to controls. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance (405{+/-}118m vs 517{+/-}106m in controls, p<0.0001) were significantly reduced in patients. The extent of extra-pulmonary MRI abnormalities and exercise tolerance correlated with serum markers of ongoing inflammation and severity of acute illness. Patients were more likely to report symptoms of moderate to severe anxiety (35% versus 10%, p=0.012) and depression (39% versus 17%, p=0.036) and a significant impairment in all domains of quality of life compared to controls. InterpretationA significant proportion of COVID-19 patients discharged from hospital experience ongoing symptoms of breathlessness, fatigue, anxiety, depression and exercise limitation at 2-3 months from disease-onset. Persistent lung and extra-pulmonary organ MRI findings are common. In COVID-19 survivors, chronic inflammation may underlie multiorgan abnormalities and contribute to impaired quality of life. FundingNIHR Oxford and Oxford Health Biomedical Research Centres, British Heart Foundation Centre for Research Excellence, UKRI, Wellcome Trust, British Heart Foundation.

Clinical study of 21 cases of sacral cysts containing fila terminale / 北京大学学报(医学版)

OBJECTIVE@#To summarize the characteristics of sacral cysts containing fila terminale and to explore the surgical treatment methods.@*METHODS@#The clinical features, imaging characteristics and surgical methods of 21 cases of sacral cysts containing fila terminale from July 2010 to March 2017 were reviewed and analyzed. Lumbosacral and perineal pain, weakness of the lower limbs and bladder and bowel dysfunction were the common clinical symptoms. MRI showed that the cysts located in the sacral canal. The lower T1 and higher T2 signals were found on MRI. There were fila terminale within the cysts which tethered the spinal cord. No enhancement was visible within the lesion. The key steps of operation included the resection of the cyst wall, the cutting off of the fila terminale, the release of the tethered cord and the reconstruction of the cisterna terminalis.@*RESULTS@#The total and subtotal resections of cyst walls were achieved in 14 and 7 cases, respectively. The fila terminales were separated and cut off in all the cases, and the tethered cords were released completely. The reconstructions of the cisterna terminalis were accomplished in all the cases. There was no new-onset dysfunction except for 7 cases of mild numbness around anus postoperatively. Pathological examinations confirmed that the cyst wall was fibrous connective tissue, and hyperplasia of fibrous tissue and/or adipose tissue was found within the thickened fila terminale. The lumbosacral and perineal pain disappeared. The weakness of the lower extremities and the bladder and bowel dysfunction gradually improved. The period of follow-up ranged from 3 months to 7 years (average: 2.25 years). The spinal function of all the patients restored to McCormick grade Ⅰ. Only 1 case encountered recurrence of cyst.@*CONCLUSION@#The sacral cysts containing fila terminale are rare. The common symptoms include lumbosacral and perineal pain and symptoms of tethered cord. MRI is helpful to the diagnosis, which shows the signal of cerebrospinal fluid and the fila terminale in the cyst as well as tlow-placed conus medullaris. Microsurgery should remove the cyst wall, cut off the fila terminale, release the tethered cord and reconstruct the cisterna terminalis.

Comparative clinical study on seldom segment with multiple segment intramedullary primary spinal cord tumors / 北京大学学报(医学版)

OBJECTIVE@#Several clinical studies were performed on multi-segment intramedullary primary spinal cord tumors. However, no clinical study focused on the relationship between different vertebral segments intramedullary tumors involvement and neurological functions, as well as prognosis of the patients. This prospective study was performed to compare clinical analysis on neurological functions and prognosis of the patients with intramedullary spinal cord primary tumors.@*METHODS@#A prospective cohort study was performed in a single medical center, Neurosurgical Department, Peking University Third Hospital. Between Jan. 1, 2010 and Dec. 30, 2015, 135 patients underwent microsurgery for intramedullary primary spinal cord tumors. The intramedullary tumor length occupying 3 or more vertebral body levels was considered as multiple segments intramedullary primary spinal cord tumor, and occupying one or two vertebral body levels considered as seldom segments. Preoperative and postoperative functions were assessed using IJOA (improved Japanese orthopaedic association) scoring system, and analyzed using the appropriate statistical tests.@*RESULTS@#Among the 135 patients, 52 cases had seldom segments intramedullary primary spinal cord tumors, and 83 cases had multiple segments. In the seldom group, 32 (62%) patients presented with normal urine and stool function, 8 (15%) patients with severe dysfunction, 7 (14%) with slight dysfunction, and 5 (9%) with incontinence, and 30 (58%) patients demonstrated various degrees of limbs weakness. The preoperative IJOA scores of the patients were 16.9±2.4. The postoperative IJOA scores at the end of 3 months were 16.6±2.3. The current IJOA scores until the end of the follow-up were 17.5±4.4. In the multiple group, 37 (45%) patients presented with normal urine and stool functions, 26 (31%) patients with slight dysfunction, 11 (13%) with severe dysfunction, and 9 (11%) with incontinence, and 62 (75%) patients demonstrated various degrees of limbs weakness. The preoperative IJOA scores of the patients were 15.6±3.4. The postoperative IJOA scores at the end of 3 months were 15.5±3.8. The current IJOA scores until the end of the follow-up were 16.9±5.8. The difference of presenting urine and stool dysfunction (Z=-1.35, P=0.18) was not statistically significant between the different patient groups. However, the difference of presenting limbs weakness (Z=-2.06, P=0.04) was statistically significant between the two groups. Most patients with multiple segment intramedullary tumors suffered from various limbs weakness. The difference of the preoperative IJOA score (P=0.02) and the postoperative early IJOA score (P=0.004) of the patients was statistically significant between the seldom and multiple segments groups. Preoperative and early postoperative neurological function of the patients was better with seldom segments tumor than with multiple segments tumor. Most patients with multi-segment intramedullary tumors experienced various limbs weakness. However, the difference of long-term neurological function (P=0.12) between the seldom and multiple segments groups was not statistically significant. The neurological function of the patients with multiple segments intramedullary tumor was remarkably improved after physical therapy.@*CONCLUSION@#Perioperative neurological function of the patients with seldom segments primary tumor was superior to that of the patients with multiple segments primary tumor, especially for limb strength. The neurological function of the patients with multiple segments intramedullary primary tumor was remarkably improved after physical therapy during long-term follow-up.

Systematic review of Shenqi Fuzheng Injection combined with chemotherapy for treatment of breast cancer / 中国中药杂志

Databases including China Biological Medicine database(CBM), Chinese scientific journals full-text database(VIP), China National Knowledge Infrastructure database(CNKI), WanFang Data, PubMed, and EMbase were searched from inception to March 2018 to collect the randomized controlled trials(RCTs) on Shenqi Fuzheng Injection combined with chemotherapy for the treatment of breast cancer. All included studies were critically appraised by two independent reviewers by following the cochrane systematic review method and using Revman 5.3 software and State 12.0 for data analysis. After screening, 20 RCTs involving 2 095 patients were included in the study. Meta-analysis showed that as compared with control group of chemotherapy alone, Shenqi Fuzheng Injection combined with chemotherapy could improve the clinical curative efficiency, the KPS score, and immune function indexes such as total T cells, Th cells and Ts cells; inhibit the decline of white blood cells(WBC), platelets in blood system, T-lymphocyte subsets such as CD3~+, CD4~+, CD4~+/CD8~+, alleviate myelosuppression and reduce the incidence of side effects such as gastrointestinal adverse reaction, liver and kidney dysfunction and abnormal electrocardiogram. The results revealed that for clinical breast cancer patients, Shenqi Fuzheng Injection combined with chemotherapy could significantly improve its clinical efficacy and reduce adverse reactions. However, the conclusions still need to be verified by high-quality, multi-center, large-sample, prospective, randomized and double-blind clinical trials. In conclusion, this study has systemically evaluated the efficacy and safety of Shenqi Fuzheng Injection combined with chemotherapy in treatment of breast cancer and provided the reference of evidence-based medicine for safe and effective clinical application of medicines.

Analysis of Clinical Application of Angiotensin Receptor Enkephalinase Inhibitor Sacubitril Valsartan in 61 Patients with Heart Failure / 中国药房

OBJECTIVE： To investigate the clinical application of angiotensin receptor enkephalinase inhibitor sacubitril valsartan in patients with heart failure， and to provide reference for its standardized use. METHODS： The electronic medical records of inpatients with heart failure using sacubitril valsartan in cardiovascular medicine department of the First Affiliated Hospital of Soochow University were collected from hospital information system during Oct. 2017 to Jun. 2018. Those medical records were analyzed statistically in respects of indication， contraindications， usage and dosage， conversion with angiotensin converting enzyme inhibitor （ACEI） or angiotensin Ⅱ receptor antagonist （ARB）， ADR and standard-reaching rate of target dose， etc. RESULTS： A total of 61 patients were given sacubitril valsartan， among which there were 7 cases （11.48％） without indication and 5 cases （8.20％） with contraindications. There were 34 cases （55.74％） with unreasonable initial dose， 4 cases （6.56％） with unreasonable frequency， 7 cases （11.48％） with unreasonable conversion with ACEI， 2 cases （3.28％） with unreasonable conversion with ARB. 9 cases （14.75％） suffered from ADR. All patients did not reach the target dose， but 27 patients （44.26％） met the target blood pressure. CONCLUSIONS： There is still a certain gap between clinical application of sacubitril valsartan and 2016 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure and 2017 Guideline for the Management of Heart Failure， mainly involving indication， contraindications， usage and dosage， drug conversion， etc. Specially the initial dosage is generally low. It is suggested that its clinical application should be further standardized by means of real-time checking and regular evaluation.