Lidar AOD inversion and aerosol extinction profile correction method based on GA-BP neural network.

Lidar is an effective remote sensing method to obtain the vertical distribution of aerosols, and how to select the aerosol extinction-backscattering ratio (AE-BR) during the inversion process is a key step to guarantee the accuracy of the lidar inversion of aerosol optical thickness (AOD) and aerosol extinction coefficient profile (AECP). In this paper, an inversion algorithm for AOD and AECP based on a genetic BP (GA-BP) neural network is proposed. Simultaneous measurements are carried out using CE318 sun photometer and lidar, and the mapping relationship between the lidar echo signal and AOD is established based on the genetic BP (GA-BP) neural network method, which achieves the accurate inversion of AOD with an absolute error mean value of 0.0156. Based on the AOD output from the GA-BP neural network, the real-time best AE- BR to improve the inversion accuracy of AECP. Finally, practical tests show that the method achieves accurate inversion of AOD, determines the range of AE-BR from 20-50sr, realizes real-time dynamic correction of AECP, and has strong generalization ability and applicability in practical situations.

Effectiveness and Safety of Anlotinib Combined with PD-1 Blockades in Patients with Previously Immunotherapy Treated Advanced Non-Small Cell Lung Cancer: A Retrospective Exploratory Study.

Objective: This study aimed to investigate the effectiveness and tolerability of anlotinib plus PD-1 blockades in patients with previously immunotherapy treated advanced non-small-cell lung cancer (NSCLC). Methods: A total of 67 patients with previously immunotherapy treated advanced NSCLC who received anlotinib plus PD-1 blockades in clinical practice were screened retrospectively. All the PD-1 blockades used in this study were approved in China and consisted of sintilimab, camrelizumab, tislelizumab and pembrolizumab. Effectiveness and safety of anlotinib plus PD-1 blockades were assessed, and all patients were followed up regularly. Clinical significance between response status to previous immune-related treatment regimens and therapeutic outcomes of anlotinib plus PD-1 blockades was further explored. Results: The best overall response among the 67 patients suggested that a partial response was observed in 16 patients, stable disease was noted in 41 patients and progressive disease was found in 10 patients, which yielded an objective response rate of 23.9% (95% CI: 14.3-35.9%) and a disease control rate of 85.1% (95% CI: 74.3-92.6%). Prognostic outcomes indicated that the median progression-free survival (PFS) was 6.1 months (95% CI: 2.37-9.83) and the median overall survival (OS) was 16.5 months (95% CI: 10.73-22.27). Exploratory analysis highlighted that patients who were intolerant to previous immune-related regimens (17 patients) might have a superior prognosis (median OS: 22.3 months vs 12.5 months, P=0.024). Additionally, adverse reactions with any grades during anlotinib plus PD-1 blockades administration were observed in 62 patients (92.5%), of which 31 patients (46.3%) had ≥grade 3 adverse reactions. Most common adverse reactions were fatigue, hypertension, diarrhea and hepatotoxicity. Conclusion: Anlotinib plus PD-1 blockades demonstrated promising effectiveness and tolerable safety in patients with previously immunotherapy treated advanced NSCLC. Those who were intolerant to previous immune-related regimens might benefit significantly from treatment with anlotinib plus PD-1 blockades. This conclusion should be confirmed in future studies.

Discussion on the Pathogenesis of Osteonecrosis of the Femoral Head Under the System of Non-uniform Settlement During Bone Resorption and Multidimensional Composite Bowstring Working in Coordination with the Theory of Liver-Kidney and Muscle-Bone Based on the Concept of Liver and Kidney Sharing the Common Source / 广州中医药大学学报

From the perspective of the physiological basis of liver and kidney sharing the common source in traditional Chinese medicine(TCM),and by integrating the theory of kidney dominating bone,liver dominating tendon,and meridian sinew of TCM as well as the bone resorption and collapse theory,and non-uniform settlement theory and lower-limb musculoskeletal bowstring structure theory of modern orthopedics,the pathogenesis of osteonecrosis of the femoral head(ONFH)under the system of non-uniform settlement during bone resorption and multidimensional composite bowstring working in coordination with the theory of liver-kidney and muscle-bone was explored.The key to the TCM pathogenesis of ONFH lies in the deficiency of the liver and kidney,and then the imbalance of kidney yin-yang leads to the disruption of the dynamic balance of bone formation and bone resorption mediated by osteoblasts-osteoclasts,which manifests as the elevated level of bone metabolism and the enhancement of focal bone resorption in the femoral head,and then leads to the necrosis and collapse of the femoral head.It is considered that the kidney dominates bone,liver dominates tendon,and the tendon and bone together constitute the muscle-bone-joint dynamic and static system of the hip joint.The appearance of collapse destroys the originally balanced muscle-bone-joint system.Moreover,the failure of liver blood in the nourishment of muscles and tendons further exacerbates the imbalance of the soft tissues around the hip joint,accelerates the collapse of the muscle-bone-joint dynamic and static system,speeds up the process of femoral head collapse,and ultimately results in irreversible outcomes.Based on the above pathogenesis,the systematic integrative treatment of ONFH should be based on the TCM holistic concept,focuses on the focal improvement of internal and external blood circulation of the femoral head by various approaches,so as to rebuild the coordination of joint function.Moreover,attention should be paid to the physical constitution of the patients,and therapy of tonifying the kidney and regulating the liver can be used to restore the balance between osteogenesis and osteoblastogenesis,and to reconstruct the muscle-bone-joint system,so as to effectively delay or even prevent the occurrence of ONFH.

Metabolic engineering of Escherichia coli for efficient production of l-arginine.

As a semi-essential amino acid, l-arginine (l-Arg) plays an important role in food, health care, and medical treatment. At present, the main method of producing l-Arg is the use of microbial fermentation. Therefore, the selection and breeding of high-efficiency microbial strains is the top priority. To continuously improve the l-Arg production performance of the strains, a series of metabolic engineering strategies have been tried to transform the strains. The production of l-Arg by metabolically engineered Corynebacterium glutamicum (C. glutamicum) reached a relatively high level. Escherichia coli (E. coli), as a strain with great potential for l-Arg production, also has a large number of research strategies aimed at screening effective E. coli for producing l-Arg. E. coli also has a number of advantages over C. glutamicum in producing l-Arg. Therefore, it is of great significance to screen out excellent and stable E. coli to produce l-Arg. Here, based on recent research results, we review the metabolic pathways of l-Arg production in E. coli, the research progress of l-Arg production in E. coli, and various regulatory strategies implemented in E. coli.

Deepening the Action on Salt Reduction in China-suggestions on strategy and implementation plan / 中华预防医学杂志

Excessive sodium/salt intake is the leading dietary risk factor for the loss of healthy life in the Chinese population. The "Healthy China 2030" Action Plan set the goal of reducing salt intake by 20% by 2030. However, salt intake in China is still at a very high level in the world, with adults reaching 11 g/d, more than twice the recommended limit of 5 g/d. The current policies and action plans of China have targeted catering workers, children, adolescents, and home chefs in salt, oil, and sugar reduction actions. However, there are still obvious deficiencies in the coordinated promotion and implementation. This study, therefore, proposed a set of comprehensive strategies (named CHRPS that is composed of communication and education, salt reduction in home cooking, salt reduction in restaurants, reducing salt content in pre-packaged food, and surveillance and evaluation) and key implementation points for further deepening the salt reduction action in China. These strategies were developed based on the main sources of dietary sodium for Chinese residents, the status of "knowledge, attitude and practice" in salt reduction, evidence of effective intervention measures, existing policies and requirements, and the salt reduction strategies of the World Health Organization and experience from some other countries. As a scientific reference, the CHRPS strategies will help the government and relevant organizations quickly implement salt reduction work and facilitate the earlier realization of China's salt reduction goal.

Traditional Chinese medicine Pingchan granule for motor symptoms and functions in Parkinson's disease: A multicenter, randomized, double-blind, placebo-controlled study.

BACKGROUND: Pingchan granule (PCG) is a traditional Chinese medicine for Parkinson's disease (PD). HYPOTHESIS/PURPOSE: This was the first study aiming to evaluate the efficacy and safety of PCG for motor symptoms, gait impairments and quality of life in PD. STUDY DESIGN AND METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, 292 participants were included and followed for 9 months, randomly assigned at a 1:1 ratio to receive PCG or placebo. The primary outcome was the severity of motor symptoms assessed by Movement Disorder Society Unified Parkinson's Rating Scale III (MDS-UPDRS-III) motor score. Secondary outcomes included timed up and go test (TUG), functional gait assessment (FGA), freezing of gait (FOG), and quality of life assessed by Parkinson's disease questionnaire (PDQ-39). Assessments were done at baseline (T0), 3 months (T1), 6 months (T2) and 9 months (T3). TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-INR-1,701,194. RESULTS: Generalized estimating equation analyses revealed that PCG group had significantly better improvement in MDS-UPDRS-III motor score than placebo group, as well as its domain scores of axial symptoms, bradykinesia, rigidity, and tremor. Improvements of TUG time, FGA, FOG questionnaire (FOGQ), and PDQ39 scores were also observed. CONCLUSION: PCG had a long-lasting efficacy for motor symptoms and function in PD with good tolerance, supporting that PCG might be a viable alternative in the management of PD.

Transanal drainage tube for prevention of anastomotic leak after anterior resection for rectal cancer: a meta-analysis / 中华胃肠外科杂志

Objective: To assess the effectiveness of transanal drainage tube (TDT) in reducing the incidence of anastomotic leak following anterior resection in patients with rectal cancer. Methods: We conducted a systematic search for relevant studies published from inception to October 2022 across multiple databases, including PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP. Meta-analysis was performed using Review Manager 5.4 software. The primary outcomes included total incidence of anastomotic leak, grade B and C anastomotic leak rates, reoperation rate, anastomotic bleeding rate, and overall complication rate. Results: Three randomized controlled trials involving 1115 patients (559 patients in the TDT group and 556 in the non-TDT group) were included. Meta-analysis showed that the total incidences of anastomotic leak and of grade B anastomotic leak were 5.5% (31/559) and 4.5% (25/559), respectively, in the TDT group and 7.9% (44/556) and 3.8% (21/556), respectively, in the non-TDT group. These differences are not statistically significant (P=0.120, P=0.560, respectively). Compared with the non-TDT group, the TDT group had a lower incidence of grade C anastomotic leak (1.6% [7/559] vs. 4.5% [25/556]) and reoperation rate (0.9% [5/559] vs. 4.3% [24/556]), but a higher incidence of anastomotic bleeding (8.2% [23/279] vs. 3.6% [10/276]). These differences were statistically significant (P=0.003, P=0.001, P=0.030, respectively). The overall complication rate was 26.5%(74/279) in the TDT group and 27.2% (75/276) in the non-TDT group. These differences are not statistically significant (P=0.860). Conclusions: TDT did not significantly reduce the total incidence of anastomotic leak but may have potential clinical benefits in preventing grade C anastomotic leak. Notably, placement of TDT may increase the anastomotic bleeding rate.

Clinical effects of free peroneal artery perforator flaps in repairing forefoot skin and soft tissue defect wounds assisted with three-dimensional computed tomography angiography / 中华烧伤杂志

Objective: To investigate the clinical effects of free peroneal artery perforator flaps in repairing forefoot skin and soft tissue defect wounds assisted with three-dimensional computed tomography angiography (3D-CTA). Methods: A retrospective observational study was conducted. From March 2017 to September 2019, 15 patients with skin and soft tissue defect wounds in the forefoot were treated in the Department of Burn and Plastic Surgery of Yidu Central Hospital of Weifang, including 12 males and 3 females, with age of 18-60 years. The wound area on admission was 3.0 cm×3.0 cm-9.0 cm×8.0 cm. The 3D-CTA examination before operation was performed to select the peroneal artery perforating vessels with appropriate length of vascular pedicle and good blood perfusion. According to the wound area and the perforating vessels of the peroneal artery located by 3D-CTA, the peroneal artery perforator flaps of 3.5 cm×3.5 cm-9.5 cm×8.5 cm carried with lateral sural cutaneous nerve was designed and cut, and the nerve was anastomosed with the nerve of the wound. The wound in the donor site of the flap was directly sutured or covered with medium-thickness skin graft from the thigh. The consistencies of type, diameter, and perforating position of perforating vessel of the peroneal artery detected by 3D-CTA before the operation with those of the actual measurement during operation were observed. The length of time for flap cutting and the survival of the flap after operation were recorded. During follow-up of 12 months after the operation, the patients were instructed to evaluate the foot function according to the Maryland foot function score standard, and the wound healing in the donor area and the occurrence of complications affecting the motor function of limb were observed. Data were statistically analyzed with paired sample t test. Results: The types of peroneal artery perforating vessels in patients measured during the operation were septocutaneous perforator of 12 cases, musculocutaneous perforator of 2 cases, and musculomuscular septal perforator of 1 case, which were consistent with those measured by preoperative 3D-CTA. The diameter of the peroneal artery perforating vessel measured by preoperative 3D-CTA was (1.38±0.17) mm, which was close to (1.40±0.19) mm measured during the operation (t=0.30, P>0.05). The horizontal distance from the starting point of the perforating vessel to the outer edge of the shank was (42±6) mm, and the vertical distance from the starting point of the perforating vessel to the level of the lateral ankle tip was (219±14) mm measured by preoperative 3D-CTA, which were respectively close to (43±6) and (221±15) mm of intraoperative measurement (with t values of 0.46 and 0.38, respectively, P>0.05). The length of time for cutting flap was (31±6) min. All flaps survived post operation without vascular crisis. During follow-up of 12 months after the operation, the foot function was evaluated as excellent in 11 cases, good in 3 cases, and fair in 1 case, the donor site wound healed well, the scar was not noticeable with no contracture, and the motor function of joints was not affected. Conclusions: Free peroneal artery perforator flap is one of the effective methods to reconstruct skin and soft tissue defect wounds in the forefoot, and the risk of surgery can be reduced when the anatomical location of the perforating vessels is confirmed by 3D-CTA.

[Evaluation of eutrophication level changes in Baiyangdian Lake based on multiple biological groups]. / 应用多种生物类群评价白洋淀水环境质量变化.

Baiyangdian Lake is the largest shallow lake in the North China Plain. Due to the increases in upstream water consumption in recent decades, the amount of natural water entering the lake has decreased, resulting in a significant drop in the water level of Baiyangdian Lake. Severe eutrophication has occurred in Baiyangdian Lake owing to the discharge of domestic sewage around the sub-lakes. With the establishment of the Xiong'an New Area in 2017, the importance of environmental governance and protection of Baiyangdian Lake has been unprecedentedly increased. The implementation of ecological water supplement from upstream reservoirs and other basins has significantly increased water level of Baiyangdian Lake. Moreover, domestic sewage from surrounding rural areas was collected. In order to understand the current state of water quality in Baiyangdian Lake, and to evaluate the effects of the previous water replenishment and pollution control projects, we investigated water physicochemical variables and aquatic organisms of Baiyangdian Lake in August 2019. We evaluated water quality status of Baiyangdian Lake based on water quality, phytoplankton, zooplankton and macrozoobenthos, by comparing with the evaluation based on the survey data in 2010. In addition, submerged macrophytes were used to evaluate the water ecological status. The results showed that the water quality state of Baiyangdian Lake in 2019 was greatly improved compared with 2010. Among them, total phosphorus concentration decreased by 88.6%, total nitrogen concentration decreased by 83.9%, chlorophyll a concentration decreased by 47.8%, and the Seechi depth increased by 43.4%. The diversity of zooplankton and macrozoobenthos were significantly increased, the density of phytoplankton was significantly reduced, the dominant species of phytoplankton changed from a general highly eutrophic type to a eutrophic type, and the distribution of the clean-type submerged macrophytes was narrowed. The evaluation methods based on submerged macrophytes species and based on zooplankton diversity were not suitable for water quality evaluation in Baiyangdian Lake. In the early stage, the pollution source of Baiyangdian Lake was concentrated in the west, which led to lower water quality. Nowadays, due to the water replenishment from the west, north and south, the hydrodynamic conditions changed significantly. In the west, pollution control projects were carried out, and the spatial distribution of water quality in Baiyangdian Lake are showing a characteristics of homogenization.

Prediction of the progression from mild cognitive impairment to Alzheimer's disease using a radiomics-integrated model.

OBJECTIVE: This study aimed to build and validate a radiomics-integrated model with whole-brain magnetic resonance imaging (MRI) to predict the progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD). METHODS: 357 patients with MCI were selected from the ADNI database, which is an open-source database for AD with multicentre cooperation, of which 154 progressed to AD during the 48-month follow-up period. Subjects were divided into a training and test group. For each patient, the baseline T1WI MR images were automatically segmented into white matter, gray matter and cerebrospinal fluid (CSF), and radiomics features were extracted from each tissue. Based on the data from the training group, a radiomics signature was built using logistic regression after dimensionality reduction. The radiomics signatures, in combination with the apolipoprotein E4 (APOE4) and baseline neuropsychological scales, were used to build an integrated model using machine learning. The receiver operating characteristics (ROC) curve and data of the test group were used to evaluate the diagnostic accuracy and reliability of the model, respectively. In addition, the clinical prognostic efficacy of the model was evaluated based on the time of progression from MCI to AD. RESULTS: Stepwise logistic regression analysis showed that the APOE4, clinical dementia rating, AD assessment scale, and radiomics signature were independent predictors of MCI progression to AD. The integrated model was constructed based on independent predictors using machine learning. The ROC curve showed that the accuracy of the model in the training and the test sets was 0.814 and 0.807, with a specificity of 0.671 and 0.738, and a sensitivity of 0.822 and 0.745, respectively. In addition, the model had the most significant diagnostic efficacy in predicting MCI progression to AD within 12 months, with an AUC of 0.814, sensitivity of 0.726, and specificity of 0.798. CONCLUSION: The integrated model based on whole-brain radiomics can accurately identify and predict the high-risk population of MCI patients who may progress to AD. Radiomics biomarkers are practical in the precursory stage of such disease.

Computed tomography imaging features for amyloid dacryolith in the nasolacrimal excretory system: A case report.

BACKGROUND: Nasolacrimal duct obstruction leading to epiphora is a common ophthalmologic complaint, and it may derive from amyloidosis in rare cases. There are a few reports about localized amyloidosis, and amyloidosis with involvement and obstruction of the nasolacrimal duct is exceedingly rare. CASE SUMMARY: A 54-year-old male presented with a 2-year history of a lump overlying the left lacrimal sac that had grown rapidly for nearly half a year. Physical examination touched a firm lump in the left lacrimal sac. Nasal endoscopy discovered lesions in appearance of sediments with easy bleeding at the entry of the nasolacrimal duct of the left inferior nasal meatus. Computerized tomography scan revealed speckle high density in the left lacrimal sac and the dilated nasolacrimal duct. During an endoscopic exploration and excision, a large number of dacryoliths were exposed. Pathology indicated amorphous pink material and multinucleated giant cell reaction in the fibrous tissue. CONCLUSION: This case showed amyloidosis in localized form mimicking dacryolith with nasolacrimal duct obstruction. In clinical practice, we should be aware of the possibility of localized amyloidosis in the nasolacrimal excretory system.

Effect of Modified Shiquan Dabutang on Inflammatory and Bone Metabolism Indexes in Elderly Patients with Osteoporotic Intertrochanteric Fractures Due to Qi and Blood Deficiency / 中国实验方剂学杂志

Objective:To explore the application value of modified Shiquan Dabutang in the treatment of elderly patients with osteoporotic intertrochanteric fractures （OIFs） due to Qi and blood deficiency by observing its impacts on inflammatory and bone metabolism indexes. Method:Ninety-eight elderly patients admitted to our hospital for OIFs of Qi and blood deficiency syndrome from April 2018 to April 2020 were randomized into an observation group （<italic>n</italic>=49） and a control group （<italic>n</italic>=49）. Following the proximal femoral nail antirotation （PFNA） fixation， patients in the control group were treated with Guipiwan， while those in the observation group received the modified Shiquan Dabutang. The clinical efficacy， inflammatory and bone metabolism indexes， and complications were compared between the two groups after four weeks of treatment. Result:The levels of such serum indexes as fibroblast growth factor-2 （FGF-2）， osteoprotegerin （OPG）， transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁）， <italic>β</italic>-endorphin （<italic>β</italic>-EP）， bone-specific alkaline phosphatase （BALP）， and osteocalcin （BGP） in the observation group after treatment were significantly elevated as compared with those in the control group （<italic>P</italic><0.05）， whereas the serum tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） and <italic>D</italic>-dimer （<italic>D</italic>-D） declined （<italic>P</italic><0.05）. The TCM symptom score in the observation group after treatment was obviously lower than that in the control group， while the Harris Hip Score （HHS） was higher （<italic>P</italic><0.05）. The overall response rate of the observation group was 93.88% （46/49）， higher than 75.51% （37/49） of the control group （<italic>χ²</italic>=6.376， <italic>P</italic><0.05）. The total incidence of incision infection， deep vein thrombosis of lower limbs， and pulmonary infection in the control group was 24.49% （12/49）， significantly higher than 6.12% （3/49） in the observation group （<italic>χ²</italic>=6.607， <italic>P</italic><0.05）. Conclusion:The modified Shiquan Dabutang is able to alleviate inflammation， regulate bone metabolism， promote bone repair， and reduce the incidence of complications in elderly patients with OIFs due to Qi and blood deficiency.

High Prevalence of 16s rRNA Methylase Genes Among Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae Isolates in a Chinese Tertiary Hospital.

Thirty-nine carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) isolates collected from a Chinese tertiary hospital were used in the characterization of the prevalence of 16S rRNA methylase genes. In total, 66.7% (26/39) of the CR-hvKP isolates were found to carry 16S rRNA methylase genes. The most frequently detected 16S rRNA methylase gene was armA (11/26, 42.3%), followed by rmtB (8/26, 30.8%), and coexistence of both armA and rmtB (7/26, 26.9%). All the clinical isolates were found to carry at least one carbapenemase gene, with blaKPC-2 (79.5%, 31/39), blaNDM-1 (10.3%, 4/39), and cocarrying blaKPC-2 and blaNDM-1 (10.3%, 4/39). A total of 89.7% (35/39) isolates carried extended-spectrum ß-lactamase (ESBL) genes, including 61.5% (24/39) blaSHV-1, 71.8% (28/39) blaTEM-1, and 89.7% (35/39) blaCTX-M-14. All except four isolates (89.7%, 35/39) harbored quinolone resistance genes, with qnrS (82.1%, 32/39), aac(6')-Ib-cr (79.5%, 31/39), and qnrB (2.6%, 1/39). Twenty-six hvKP strains in this study were first reported to cocarry carbapenemase genes, ESBL genes, quinolone resistance genes, and 16S rRNA methylase genes simultaneously. Multilocus sequence typing (MLST) analysis assigned the 39 CR-hvKP isolates into 4 sequence types (STs), with ST11 encompassing 79.5% of the strains. Pulsed field gel electrophoresis (PFGE) typing showed that strains closely related by MLST clustered in major PFGE clusters, of which cluster A accounts for 31 ST11 isolates. Cumulatively, 16S rRNA methylase genes are highly prevalent in CR-hvKP clinical isolates especially for ST11; it is, therefore, critical to continuously monitor the epidemiology of these 16S rRNA methylase-producing CR-hvKP while simultaneously minimizing potential risks from aminoglycoside-resistant CR-hvKP.

SARS-CoV-2 seroprevalence and transmission risk factors among high-risk close contacts: a retrospective cohort study.

BACKGROUND: The proportion of asymptomatic carriers and transmission risk factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among household and non-household contacts remains unclear. In Singapore, extensive contact tracing by the Ministry of Health for every diagnosed COVID-19 case, and legally enforced quarantine and intensive health surveillance of close contacts provided a rare opportunity to determine asymptomatic attack rates and SARS-CoV-2 transmission risk factors among community close contacts of patients with COVID-19. METHODS: This retrospective cohort study involved all close contacts of confirmed COVID-19 cases in Singapore, identified between Jan 23 and April 3, 2020. Household contacts were defined as individuals who shared a residence with the index COVID-19 case. Non-household close contacts were defined as those who had contact for at least 30 min within 2 m of the index case. All patients with COVID-19 in Singapore received inpatient treatment, with access restricted to health-care staff. All close contacts were quarantined for 14 days with thrice-daily symptom monitoring via telephone. Symptomatic contacts underwent PCR testing for SARS-CoV-2. Secondary clinical attack rates were derived from the prevalence of PCR-confirmed SARS-CoV-2 among close contacts. Consenting contacts underwent serology testing and detailed exposure risk assessment. Bayesian modelling was used to estimate the prevalence of missed diagnoses and asymptomatic SARS-CoV-2-positive cases. Univariable and multivariable logistic regression models were used to determine SARS-CoV-2 transmission risk factors. FINDINGS: Between Jan 23 and April 3, 2020, 7770 close contacts (1863 household contacts, 2319 work contacts, and 3588 social contacts) linked to 1114 PCR-confirmed index cases were identified. Symptom-based PCR testing detected 188 COVID-19 cases, and 7582 close contacts completed quarantine without a positive SARS-CoV-2 PCR test. Among 7518 (96·8%) of the 7770 close contacts with complete data, the secondary clinical attack rate was 5·9% (95% CI 4·9-7·1) for 1779 household contacts, 1·3% (0·9-1·9) for 2231 work contacts, and 1·3% (1·0-1·7) for 3508 social contacts. Bayesian analysis of serology and symptom data obtained from 1150 close contacts (524 household contacts, 207 work contacts, and 419 social contacts) estimated that a symptom-based PCR-testing strategy missed 62% (95% credible interval 55-69) of COVID-19 diagnoses, and 36% (27-45) of individuals with SARS-CoV-2 infection were asymptomatic. Sharing a bedroom (multivariable odds ratio [OR] 5·38 [95% CI 1·82-15·84]; p=0·0023) and being spoken to by an index case for 30 min or longer (7·86 [3·86-16·02]; p<0·0001) were associated with SARS-CoV-2 transmission among household contacts. Among non-household contacts, exposure to more than one case (multivariable OR 3·92 [95% CI 2·07-7·40], p<0·0001), being spoken to by an index case for 30 min or longer (2·67 [1·21-5·88]; p=0·015), and sharing a vehicle with an index case (3·07 [1·55-6·08]; p=0·0013) were associated with SARS-CoV-2 transmission. Among both household and non-household contacts, indirect contact, meal sharing, and lavatory co-usage were not independently associated with SARS-CoV-2 transmission. INTERPRETATION: Targeted community measures should include physical distancing and minimising verbal interactions. Testing of all household contacts, including asymptomatic individuals, is warranted. FUNDING: Ministry of Health of Singapore, National Research Foundation of Singapore, and National Natural Science Foundation of China.

Multiple comorbid sleep disorders adversely affect quality of life in Parkinson's disease patients.

Sleep disorders are common non-motor symptoms in patients with Parkinson's disease (PD). The characteristics and impact of multiple comorbid sleep disorders remain to be elucidated. Our goal was to investigate the characteristics of various sleep disorder comorbidities, and their association with motor complications and the impact on the quality of life in PD patients. In this multicenter, observational, cross-sectional study, data concerning the clinical characteristics of complicated sleep disorders were collected from PD patients treated at 40 different hospitals in Shanghai. Sleep disorders were evaluated using the PD Sleep Scale-2, Epworth Sleepiness Scale, Rapid Eye Movement Sleep Behavior Disorder Questionnaire-Hong Kong, and the International Restless Legs Scale. Among the 1006 subjects evaluated, 77.53% exhibited signs of sleep disorders, and most had multiple sleep disorders (n = 502, 49.9%). A smaller percentage of patients with sleep disorders had a single disorder (n = 278, 27.6%). Furthermore, an increased number of sleep disorders, including nighttime problems, excessive daytime sleepiness, rapid eye movement sleep behavior disorder, and restless legs syndrome was a significant contributor to a poor quality of life (ß = 4.33, CI: 3.33-5.33, P for trend <0.001), even when controlling for multiple factors. Moreover, motor complications partially mediated this relationship (indirect effect: ß = 0.355, 95% boot CI: 0.134, 0.652).Our study showed that a large proportion of PD patients suffer from multiple comorbid sleep disorders, which greatly decreases the quality of life in PD patients and is partially mediated by motor complications.

Effect of roux-en Y gastric bypass surgery on patients with type 2 diabetes mellitus: A protocol of systematic review and meta-analysis.

BACKGROUND: Previous studies have reported that roux-en Y gastric bypass surgery (RYGBS) can benefit patients with type 2 diabetes mellitus (T2DM). However, their conclusions are still inconsistent. Thus, this study will aim to assess the effect of RYGBS for patients with T2DM. METHODS: In this study, the electronic databases of MEDLINE, EMBASE, CENTRAL, CINAHL, AMED, and CNKI from inceptions to the present without any limitations to language and publication status. All randomized controlled trials on assessing the effect of RYGBS for patients with T2DM will be included in this study. Two independent authors will carry out study search and selection according to the previous designed inclusion and exclusion criteria. At the same time, 2 authors will independently evaluate the risk of bias assessment by Cochrane risk of bias tool. Any disagreements between 2 authors will be solved by a third author through discussion. RevMan 5.3 software will be utilized for statistical analysis. RESULTS: This study will summarize the most recent studies and will provide a deeper understanding about using the effect of RYGBS for patients with T2DM. CONCLUSIONS: The findings of this study will present the existing evidence for the effect of RYGBS for patients with T2DM. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040127.

Efficacy of laparoscopic sleeve gastrectomy in obese patients with type 2 diabetes mellitus: A protocol of systematic review and meta-analysis.

BACKGROUND: A numerous studies have reported that obese patients (OP) are easily to have type 2 diabetes mellitus (T2DM). Although a variety of managements are available to treat such disorder, their efficacy is still limited. Previous studies have reported that laparoscopic sleeve gastrectomy (LSGT) can benefit OP with T2DM. However, no study specifically and systematically explores this topic. Thus, this study will assess the efficacy and complications of LSGT for the management of OP with T2DM. METHODS: The search strategy will be performed in the electronic databases from inception to the March 31, 2020 without limitations of language and publication time: PUBMED, EMBASE, Cochrane Library, Scopus, Web of Science, CINAHL, AMED, WANGFANG, VIP, and CNKI. Two authors will independently identify the articles, collect the data, and assess the risk of bias using Cochrane risk of bias tool. We will invite a third author to solve any differences between two authors. We will use RevMan 5.3 software to investigate the statistical analysis. RESULTS: This study will supply a high-quality synthesis of randomized controlled trials (RCTs) on the analysis of LSGT for the management of OP with T2DM. CONCLUSIONS: This study will help to build proposals that aim at providing high quality RCTs in the management of LSGT in OP with T2DM. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040128.

2-Pyrazine-PPD, a novel dammarane derivative, showed anticancer activity by reactive oxygen species-mediate apoptosis and endoplasmic reticulum stress in gastric cancer cells.

20 (R)-Dammarane-3ß, 12ß, 20, 25-tetrol (25-OH-PPD), a ginsenoside, was derived from Panax ginseng (C. A. Meyer) and inhibited growth of several cancer cell lines. To improve the anti-cancer activity, we introduced the pyrazine ring to 25-OH-PPD and obtained the compound 20(R)-[2,3-ß]-Pyrazine-dammarane-12ß,20,25-triol (2-Pyrazine-PPD). we evaluated the anti-cancer activity of 2-Pyrazine-PPD and investigated the main anti-cancer mechanisms of 2-Pyrazine-PPD in gastric cancer cells. We found that 2-Pyrazine-PPD remarkably suppressed the proliferation of gastric cancer cells in a concentration-dependent, and showed little toxicity to the normal cell (human gastric epithelial cell line-GES-1). Further study indicated that 2-Pyrazine-PPD induced apoptosis by mitochondria pathway in BGC-803 cancer cells, and activated unfolded protein response and the protein kinase RNA-activated (PKR)-like ER kinase (PERK)/Eukaryotic translation initiation factor-2α (eIF-2α)/Activating transcription factor 4 (ATF4) axis, the expression level of the protein C/EBP homologous protein (CHOP), the marker of endoplasmic reticulum stress, and the apoptosis inducing by 2-Pyrazine-PPD can partly be inhibited by siRNA-mediated knockdown of CHOP. Moreover, the production of reactive oxygen species was remarkably up-regulated in BGC-803 cancer cells treated with 2-Pyrazine-PPD. N-acetylcysteine (NAC, a reactive oxygen species scavenger) can attenuate 2-Pyrazine-PPD-induced apoptosis and endoplasmic reticulum stress. Taken together, we suggested that 2-Pyrazine-PPD exhibited remarkable anti-cancer activity by reactive oxygen species-mediate cell apoptosis and endoplasmic reticulum stress in gastric cancer cells. Our results uncovered the mechanism of 2-Pyrazine-PPD as a promising anti-tumor candidate for gastric cancer therapy.

Acquisition of Plasmid with Carbapenem-Resistance Gene blaKPC2 in Hypervirulent Klebsiella pneumoniae, Singapore.

The convergence of carbapenem-resistance and hypervirulence genes in Klebsiella pneumoniae has led to the emergence of highly drug-resistant superbugs capable of causing invasive disease. We analyzed 556 carbapenem-resistant K. pneumoniae isolates from patients in Singapore hospitals during 2010-2015 and discovered 18 isolates from 7 patients also harbored hypervirulence features. All isolates contained a closely related plasmid (pKPC2) harboring blaKPC-2, a K. pneumoniae carbapenemase gene, and had a hypervirulent background of capsular serotypes K1, K2, and K20. In total, 5 of 7 first patient isolates were hypermucoviscous, and 6 were virulent in mice. The pKPC2 was highly transmissible and remarkably stable, maintained in bacteria within a patient with few changes for months in the absence of antimicrobial drug selection pressure. Intrapatient isolates were also able to acquire additional antimicrobial drug resistance genes when inside human bodies. Our results highlight the potential spread of carbapenem-resistant hypervirulent K. pneumoniae in Singapore.