Detection of pTDP-43 via routine muscle biopsy: A promising diagnostic biomarker for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.

Exploring long-term changes and influencing factors of the upper airway in patients with a skeletal Class II relationship after mandibular advancement with maxillary setback surgery: A comprehensive 2-year follow-up investigation.

INTRODUCTION: The objective of this study was to investigate the 2-year postoperative change and influencing factors of the upper airway after mandibular advancement with maxillary setback surgery for patients with a skeletal Class II relationship. METHODS: Fifty-seven participants who underwent mandibular advancement with maxillary setback surgery were enrolled consecutively. Cone-beam computed tomography was performed preoperatively, 3 months postoperatively (T1), and 2 years (T2) postoperatively. All parameters were measured using Dolphin Imaging software (Dolphin Imaging and Management Solutions, Chatsworth, Calif). RESULTS: The total volume (V), minimum cross-sectional area (CSAmin), and glossopharynx increased significantly in both the short-term (V, 13.33%; CSAmin, 33.03%; glossopharynx, 26.73%) and long-term (V, 10.19%; CSAmin, 23.18%; glossopharynx, 18.27%) after the surgery. Mandibular advancement, mandibular width increase, preoperative CSAmin, and body mass index (BMI) significantly affected 2-year postoperative V increases. Mandibular advancement and BMI significantly affected 2-year postoperative glossopharynx increases. Backward movement of point PNS may lead to a reduction of the nasopharynx; however, downward movement of point PNS, upward movement of point A, and increased maxillary width may compensate for this effect by increasing the likelihood of the nasopharynx opening. Furthermore, mandibular body length at T1 is positively associated with relapse rate ([T2 - T1] / T1) of V and CSAmin. CONCLUSIONS: Mandibular advancement amount, mandibular width increase, preoperative CSAmin, and BMI are the 4 factors for long-term V changes. Patients with a longer mandibular body length might have a lower relapse rate.

Simple and sensitive sandwich-like voltammetric immunosensing of procalcitonin.

Procalcitonin (PCT) is a reliable biomarker in the early diagnosis of septicemia, pyemia and stroke-associated pneumonia. In this work, through preparing ß-cyclodextrin/graphene (CD/GN) nanohybrid as carrier and amplifier simultaneously to band antibodies and probe molecules, a simple and innovative sandwich-like voltammetric immunosensor was proposed for the sensitive and effective determination of PCT. Owing to the host-guest recognition property, the antibodies of PCT can enter into the CD cavities to generate a stable complex; meanwhile, aminopyrene (AP) were introduced as the signal probe and it was adsorbed on the surface of GN via aminopyrine π-πinteraction. Based on the signal change from AP as a response signal which exhibits linearity to the concentration of PCT, a highly sensitive sandwich-type voltammetric immunosensor was developed successfully after optimizing various key parameters. The results demonstrated that the developed sensor had a considerably low detection limit (0.003 pg mL-1) and wide linearity of 0.01 pg mL-1 to 20.0 ng mL-1. This work offered a very simple and sensitive sensing strategy for PCT and other biomarkers via altering the specific antibodies simply, showing great potential applications.

The efficacy and feasibility of neoadjuvant immunotherapy plus chemotherapy followed by McKeown minimally invasive oesophagectomy for locally advanced oesophageal squamous cell carcinoma.

Introduction: In immunotherapy, antibodies are activated to block immune checkpoints, resist tumour immunosuppression, shrink tumours and prevent a recurrence. As the science behind tumour immunotherapy continuously develops and improves, neoadjuvant immunotherapy bears more prominent advantages: antigen exposure not only enhances the degree of tumour-specific T-cell response but also prolongs the duration of actions. In this study, we evaluated the efficacy and safety of McKeown minimally invasive oesophagectomy (McKeown MIO) following neoadjuvant immunotherapy combined with chemotherapy (NICT) in patients with locally advanced oesophageal cancer (OC). Patients and Methods: In this retrospective study, 94 patients underwent either NICT or neoadjuvant chemotherapy (NCT) followed by MIO at our institution from January 2020 to October 2022. We assessed the therapy-related adverse events and perioperative outcomes and compared them between the two groups. Results: After completing at least two cycles of neoadjuvant therapy, all patients underwent McKeown MIO with negative margins within 4-7 weeks. Demographic data of the two cohorts were similar. Regarding perioperative characteristics, the median intraoperative blood loss was 50 ml in the NICT group, lower than that of the NCT group (100 ml, P < 0.05). In addition, the NICT group had significantly more harvested lymph nodes than the NCT group (P < 0.05). No significant differences were found in post-operative complications. The rate of objective response rate in the NICT group was higher than that in the NCT group (88.3% vs. 58.8%). Regarding tumour regression, the number of patients with TRG Grades 1-3 in the NICT group was more than that in the NCT. Adverse events experienced by the two groups included anaemia and elevated transaminase. We found no difference in the adverse events between the two groups. Conclusions: This study showed the efficacy and feasibility of NICT followed by McKeown MIO in treating locally advanced OC.

Dried fruit intake causally protects against low back pain: A Mendelian randomization study.

Background: Low back pain is the leading cause of years lived with disability worldwide. The aim of this study was to evaluate whether dried fruit intake causally protects against low back pain using two-sample Mendelian randomization (MR). Methods: We obtained summary-level data for dried fruit intake (N = 421,764) from the IEU Open GWAS Project. Forty-one independent genetic variants proxied dried fruit intake. The corresponding data for low back pain were derived from the FinnGen project (13,178 cases and 164,682 controls; discovery data) and the Neale lab (5,423 cases and 355,771 controls; replication data). We conducted univariable and multivariable MR analyses. Results: In the univariable MR analysis, the inverse variance weighted estimate showed that greater dried fruit intake was associated with decreased risk of low back pain [odds ratio (OR) = 0.435, 95% confidence interval (CI): 0.287-0.659, P = 8.657 × 10-5]. Sensitivity analyses using the MR-Egger (OR = 0.078, 95% CI: 0.013-0.479, P = 0.009), maximum likelihood (OR = 0.433, 95% CI: 0.295-0.635, P = 1.801 × 10-5), weighted median (OR = 0.561, 95% CI: 0.325-0.967, P = 0.038) and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) (OR = 0.454, 95% CI: 0.302-0.683, P = 4.535 × 10-4) methods showed consistent results. No evidence of directional pleiotropy was identified according to the Egger intercept (intercept P-value = 0.065) or applying the MR-PRESSO method (global test P-value = 0.164). The replication analysis yielded similar results. The multivariable MR revealed that the inverse association between dried fruit intake and low back pain was consistent after adjustment for fresh fruit intake, body mass index, current tobacco smoking, alcohol intake frequency, total body bone mineral density, serum 25-hydroxyvitamin D levels, and vigorous physical activity. Conclusion: This MR study provides evidence to support that dried fruit intake causally protects against low back pain.

Multiomics reveals an essential role of long-distance translocation in regulating plant cadmium resistance and grain accumulation in allohexaploid wheat (Triticum aestivum).

Cadmium (Cd) is a highly toxic heavy metal that readily enters cereals, such as wheat, via the roots and is translocated to the shoots and grains, thereby posing high risks to human health. However, the vast and complex genome of allohexaploid wheat makes it challenging to understand Cd resistance and accumulation. In this study, a Cd-resistant cultivar of wheat, 'ZM1860', and a Cd-sensitive cultivar, 'ZM32', selected from a panel of 442 accessions, exhibited significantly different plant resistance and grain accumulation. We performed an integrated comparative analysis of the morpho-physiological traits, ionomic and phytohormone profiles, genomic variations, transcriptomic landscapes, and gene functionality in order to identify the mechanisms underlying these differences. Under Cd toxicity, 'ZM1860' outperformed 'ZM32', which showed more severe leaf chlorosis, poorer root architecture, higher accumulation of reactive oxygen species, and disordered phytohormone homeostasis. Ionomics showed that 'ZM32' had a higher root-to-shoot translocation coefficient of Cd and accumulated more Cd in the grains than 'ZM1860'. Whole-genome re-sequencing (WGS) and transcriptome sequencing identified numerous DNA variants and differentially expressed genes involved in abiotic stress responses and ion transport between the two genotypes. Combined ionomics, transcriptomics, and functional gene analysis identified the plasma membrane-localized heavy metal ATPase TaHMA2b-7A as a crucial Cd exporter regulating long-distance Cd translocation in wheat. WGS- and PCR-based analysis of sequence polymorphisms revealed a 25-bp InDel site in the promoter region of TaHMA2b-7A, and this was probably responsible for the differential expression. Our multiomics approach thus enabled the identification of a core transporter involved in long-distance Cd translocation in wheat, and it may provide an elite genetic resource for improving plant Cd resistance and reducing grain Cd accumulation in wheat and other cereal crops.

SNHG9/miR-214-5p/SOX4 feedback loop regulates osteosarcoma progression.

Osteosarcoma (OS) is a high-grade, aggressive bone sarcoma. LncRNAs play a key regulatory role in controlling biological and pathological processes. The expression of lncRNA SNHG9 varies among different cancer tissues, and the role of SNHG9 in OS progression is unclear. In this study, we found SNHG9 overexpression in OS tissues and cells. In addition, downregulated SNHG9 expression impaired the proliferation, migration, and invasion abilities of OS cells. SNHG9 expression was positively regulated by the transcription factor SOX4. SNHG9 interacted with miR-214-5p as a molecular sponge and SOX4 was identified as the target of miR-214-5p. The interaction affected the expression of SNHG9, miR-214-5p, and SOX4, and regulated OS cell proliferation, migration, and invasion. Therefore, the SNHG9/miR-214-5p/SOX4 feedback loop performs an important role in OS progression and might be used as a new potential therapeutic target for the treatment of OS.

Synchronous Signal Transmission Method of Minimally Invasive Renal Failure Surgery Based on Nano Molecular Image Probe.

The synchronous signal transmission can promote the successful completion of minimally invasive renal failure surgery, so the synchronous signal transmission method of minimally invasive renal failure surgery based on nano molecular image probe is studied. The nanoprobe is constructed by loading different signal molecules, photosensitizers, acoustic sensitizers and thermosensitives through the method of double emulsion or film hydration; the near-infrared confocal endoscope molecular image diagnosis and treatment equipment is designed based on the nanoprobe, and the intraoperative highfrequency image is obtained through the diagnosis and treatment equipment; the high-frequency injection energy and signal synchronous transmission method is adopted, and the signal is added to the primary and secondary resonance circuit. In the coupling module, a higher frequency alternating signal is added into the resonant coupling voltage to modulate the signal into the transmission resonance system, which is transmitted from the energy transmission coupling coil to the secondary end, and the injected signal part of the coupling coil is demodulated at the other end to complete the transmission of the signal coupling transmission loop, so as to realize the high-frequency image energy and index data signal of minimally invasive renal failure surgery. The experimental results show that the designed nano molecular image probe has good stability, and the simulated signal transmission waveform is consistent with the transmission waveform of the principle analysis. Applying the proposed method to the minimally invasive surgery of renal failure, it is found that the success rate and image signal transmission efficiency of the minimally invasive surgery of patients 1-5 are higher than 99.5%, and the operation image transmission accuracy is high and the operation effect is excellent.

GGC Repeat Expansion of RILPL1 is Associated with Oculopharyngodistal Myopathy.

OBJECTIVE: Oculopharyngodistal myopathy (OPDM) is an adult-onset neuromuscular disease characterized by progressive ptosis, dysarthria, ophthalmoplegia, and distal muscle weakness. Recent studies revealed that GGC repeat expansions in 5'-UTR of LRP12, GIPC1, and NOTCH2NLC are associated with OPDM. Despite these advances, approximately 30% of OPDM patients remain genetically undiagnosed. Herein, we aim to investigate the genetic basis for undiagnosed OPDM patients in two unrelated Chinese Han families. METHODS: Parametric linkage analysis was performed. Long-read sequencing followed by repeat-primed polymerase chain reaction and amplicon length polymerase chain reaction were used to determine the genetic cause. Targeted methylation sequencing was implemented to detect epigenetic changes. The possible pathogenesis mechanism was investigated by quantitative polymerase chain reaction, immunoblotting, RNA fluorescence in situ hybridization, and immunofluorescence staining of muscle biopsy samples. RESULTS: The disease locus was mapped to 12q24.3. Subsequently, GGC repeat expansion in the promoter region of RILPL1 was identified in six OPDM patients from two families, findings consistent with a founder effect, designated as OPDM type 4. Targeted methylation sequencing revealed hypermethylation at the RILPL1 locus in unaffected individuals with ultralong expansion. Analysis of muscle samples showed no significant differences in RILPL1 mRNA or RILPL1 protein levels between patients and controls. Public CAGE-seq data indicated that alternative transcription start sites exist upstream of the RefSeq-annotated RILPL1 transcription start site. Strand-specific RNA-seq data revealed bidirectional transcription from the RILPL1 locus. Finally, fluorescence in situ hybridization/immunofluorescence staining showed that both sense and antisense transcripts formed RNA foci, and were co-localized with hnRNPA2B1 and p62 in the intranuclear inclusions of OPDM type 4 patients. INTERPRETATION: Our findings implicate abnormal GGC repeat expansions in the promoter region of RILPL1 as a novel genetic cause for OPDM, and suggest a methylation mechanism and a potential RNA toxicity mechanism are involved in OPDM type 4 pathogenesis. ANN NEUROL 2022;92:512-526.

Identification of SSBP1 as a prognostic marker in human lung adenocarcinoma using bioinformatics approaches.

OBJECTIVE: Single-stranded DNA-binding protein 1 (SSBP1) plays an important role in DNA repair processes and the maintenance of genomic stability. The aim of this study was to evaluate the expression of SSBP1 and its prognostic value in lung adenocarcinoma (LUAD) using bioinformatics approaches. METHODS: We applied databases including UALCAN, Kaplan-Meier plotter, LinkedOmics, Webgestalt, cBioPortal and TIMER2.0 in this study. RESULTS: We found that SSBP1 expression was up-regulated in LUAD samples and was correlated with clinicopathological features including age, cancer stage, and nodal metastasis status by the UALCAN analysis. Multivariate Cox regression analysis by the Kaplan-Meier plotter showed that high SSBP1 expression was independently correlated with poor overall survival (hazard ratio = 1.63, 95% confidence interval: 1.08-2.46, logrank P = 0.02). The LinkedOmics analysis showed that 5078 genes were positively correlated with SSBP1 expression, whereas 7905 genes were negatively correlated with SSBP1 in LUAD. Functional enrichment analysis using the Webgestalt tool showed that for SSBP1 and the genes positively correlating with it, the significantly enriched biological process was ribosomal large subunit biogenesis, and the significantly enriched pathway was proteasome. According to the cBioPortal database, the frequency of SSBP1 alterations was 1.7% in LUAD patients, and patients with SSBP1 alterations had worse prognosis (logrank P = 4.26e-05) compared with those unaltered for SSBP1. Finally, SSBP1 expression was negatively correlated with B cell infiltration level (Rho = -0.193, P = 1.54e-05) and the expression of B cell biomarkers including CD79A and CD19. CONCLUSION: Our results suggest that SSBP1 may be a prognostic marker for human LUAD.

Paeoniflorin Enhances the Sensitivity of ER-Positive Breast Cancer Cells to Tamoxifen through Promoting Sirtuin 4.

Tamoxifen is an effective drug for treating patients with advanced estrogen receptor-positive (ER+) breast cancer (BC), but not for all ER + BC patients. Drug tolerance is the biggest obstacle. In this study, we designed an experiment to investigate whether paeoniflorin affects the ER + BC cell's sensitivity to tamoxifen in the T47D and MCF-7 cell lines. Herein, we found that paeoniflorin inhibited cell proliferation without inducing apoptosis. However, it enhanced tamoxifen-induced apoptosis in both cell lines. Immunoblotting revealed that paeoniflorin significantly increased the already elevated Bax/Bcl2 protein expression ratio and the caspase 3 activity levels, both induced by tamoxifen. Paeoniflorin was also found to increase SIRT4 expression, and deletion of SIRT4 could significantly reverse the inhibition of cell proliferation induced by paeoniflorin and significantly decrease paeoniflorin-enhanced apoptosis induced by tamoxifen. Moreover, protein expression detection revealed that paeoniflorin enhanced the tamoxifen-induced inhibition of STAT3 activation. Besides, the deletion of SIRT4 could significantly increase STAT3 activation in the T47D and MCF-7 cells. In conclusion, paeoniflorin suppressed STAT3 activation to enhance the sensitivity of ER-positive breast cancer cells to tamoxifen through promoting SIRT4 expression.

Circ_0005875 sponges miR-502-5p to promote renal cell carcinoma progression through upregulating E26 transformation specific-1.

Increasing evidence has shown that circular RNAs (circRNAs) play critical roles in various cancers, including renal cell carcinoma (RCC). We aimed to explore the role and underlying mechanism of circ_0005875 in RCC. The expression levels of circ_0005875, microRNA-502-5p (miR-502-5p) and E26 transformation specific-1 (ETS1) mRNA were determined by quantitative real-time PCR. Cell proliferation was assessed by Cell Counting Kit-8, colony formation, and 5-Ethynyl-2'-deoxyuridine (EdU) assays. Cell migration and invasion were monitored by wound healing assay and transwell assay, respectively. Flow cytometry analysis was applied to determine cell apoptosis and cell cycle distribution. Western blot assay was performed to measure the protein expression of CyclinD1 and ETS1. The interaction between miR-502-5p and circ_0005875 or ETS1 was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. A xenograft tumor model was established to confirm the role of circ_0005875 in vivo. Circ_0005875 and ETS1 were upregulated and miR-502-5p was downregulated in RCC tissues and cells. Knockdown of circ_0005875 suppressed RCC cell proliferation, migration and invasion, and induced apoptosis and cell cycle arrest. MiR-502-5p was a target of circ_0005875, and miR-502-5p inhibition reversed the inhibitory effects of circ_0005875 knockdown on the malignant behaviors of RCC cells. ETS1 was a direct target of miR-502-5p, and miR-502-5p exerted its anti-tumor role in RCC cells by targeting ETS1. Moreover, circ_0005875 knockdown decreased ETS1 expression by sponging miR-502-5p. Additionally, circ_0005875 depletion suppressed tumor growth in vivo. Circ_0005875 knockdown suppressed RCC progression by regulating miR-502-5p/ETS1 axis, which might provide a promising therapeutic target for RCC.

Feasibility of utilizing ultra-low-dose contrast medium for pancreatic artery depiction using the combination of advanced virtual monoenergetic imaging and high-concentration contrast medium: an intra-patient study.

OBJECTIVES: The least amount of contrast medium (CM) should be used under the premise of adequate diagnosis. The purpose of this study is to evaluate the feasibility of utilizing ultra-low-dose (224 mgI/kg) CM for pancreatic artery depiction using the combination of advanced virtual monoenergetic imaging (VMI+) and high-concentration (400 mgI/mL) CM. MATERIALS AND METHODS: 41 patients who underwent both normal dose CM (ND-CM, 320 mgI/kg) and low dose CM (LD-CM, 224 mgI/kg) thoracoabdominal enhanced CT for tumor follow-up were prospectively included. The VMI+ at the energy level of 40-kev for LD-CM images was reconstructed. CT attenuation, signal-to-noise ratios (SNRs), and contrast-to-noise ratios (CNRs) of the abdominal artery, celiac artery, and superior mesenteric artery (SMA) and qualitative scores of pancreatic arteries depiction were recorded and compared among the three groups (ND-CM, LD-CM, and VMI+ LD-CM images). ANOVA and Friedman tests were used for statistical analysis. RESULTS: All quantitative and qualitative parameters on LD-CM images were lower than that on ND-CM images (all p < 0.01). There were no significant differences of all arteries' qualitative scores between ND-CM and VMI+ LD-CM images (all p > 0.05). VMI+ LD-CM images had the highest mean CT and CNR values of all arteries (all p < 0.0001). The CM volume was 52.6 ± 9.4 mL for the ND-CM group and 37.0 ± 6.7 mL for the LD-CM group. CONCLUSION: Ultra-low-dose CM (224 mgI/kg) was feasible for depicting pancreatic arteries. Inferior angiographic image quality could be successfully compensated by VMI+ and high-concentration CM.

Strontium-Loaded Nanotubes of Ti-24Nb-4Zr-8Sn Alloys for Biomedical Implantation.

Ti-24Nb-4Zr-8Sn (Ti2448) alloys, with a relatively low elastic modulus and unique mechanical properties, are desirable materials for oral implantation. In the current study, a multifaceted strontium-incorporating nanotube coating was fabricated on a Ti2448 alloy (Ti2-NTSr) through anodization and hydrothermal procedures. In vitro, the Ti2-NTSr specimens demonstrated better osteogenic properties and more favorable osteoimmunomodulatory abilities. Moreover, macrophages on Ti2-NTSr specimens could improve the recruitment and osteogenic differentiation of osteoblasts. In vivo, dense clots with highly branched, thin fibrins and small pores existed on the Ti2-NTSr implant in the early stage after surgery. Analysis of the deposition of Ca and P elements, hard tissue slices and the bone-implant contact rate (BIC%) of the Ti2-NTSr implants also showed superior osseointegration. Taken together, these results demonstrate that the Ti2-NTSr coating may maximize the clinical outcomes of Ti2448 alloys for implantation applications.

Surface Acoustic Wave DMMP Gas Sensor with a Porous Graphene/PVDF Molecularly Imprinted Sensing Membrane.

In this paper, surface acoustic wave (SAW) sensors containing porous graphene/PVDF (polyvinylidene fluoride) molecularly imprinted sensitive membrane for DMMP gas detection were investigated. A 433 MHz ST-cut quartz SAW resonator was used to convert gas concentration changes into frequency shifts by the sensors. The porous graphene/PVDF film was fabricated on the sensor's surface by using the tape-casting method. DMMP molecules were adsorbed on the porous structure sensing film prepared by the 2-step method to achieve the specific recognition effect. The sensitivity of the sensor could reach -1.407 kHz·ppm-1. The response time and recovery time of the SAW sensor with porous graphene/PVDF sensing membrane were about 4.5 s and 5.8 s at the concentration of 10 ppm, respectively. The sensor has good anti-interference ability to most gases in the air.

Learning Curve for Lymph Node Dissection Around the Recurrent Laryngeal Nerve in McKeown Minimally Invasive Esophagectomy.

BACKGROUND: Compared to open esophagectomy (OE), minimally invasive esophagectomy (MIE) is associated with lower morbidity and mortality. However, lymph node (LN) dissection around the recurrent laryngeal nerve (RLN) is still an important factor that affects the length of the learning curve of MIE. This study aims to evaluate the surgical outcomes of the first nearly 5-year period and explore the learning curve for LN dissection around the RLN in McKeown MIE by a new single surgical team. METHODS: A total of 285 consecutive patients who underwent McKeown MIE between March 2016 and September 2020 were included at our institution. According to the cumulative sum (CUSUM) analysis of LN dissection around the RLN, the patients were divided into three groups: exploration period, adjustment period, and stable period. We assessed the impact of surgical proficiency on postoperative outcomes and explored the learning curve for LN dissection around the RLN in McKeown MIE. RESULTS: The CUSUM graph showed that a point of upward inflection for LN dissection around the RLN was observed in 151 cases. After 151 cases, LNs around the right and left RLNs were dissected thoroughly compared to the exploration and adjustment period (P = 0.010 and P = 0.012, respectively), and the postoperative incidence of hoarseness significantly decreased from 11.1 to 1.5% (P<0.001). CONCLUSIONS: Our study results revealed that not only are the LN, around the RLN, sufficiently dissected but also the incidence of hoarseness significantly decreased in the stable phase. Consequently, the learning curve length was approximately 151 cases for LN dissection around the RLN in McKeown MIE.

Bioactivity-guided discovery of quality control markers in rhizomes of Curcuma wenyujin based on spectrum-effect relationship against human lung cancer cells.

BACKGROUND: Due to the diversity of the ingredients, the complexity of the mechanism of action, the uncertainty of the effective ingredients, coupled with the multiple species and multiple growing areas, the quality control (QC) of Traditional Chinese Medicines (TCMs) is challenging. Discovering and identifying effective compounds from the complex extracts of TCMs and then establishing a scientific QC method is the key to the holistic QC of TCMs. PURPOSE: To develop an anti-lung-cancer-guided spectrum-effect relationship approach for the discovery of QC markers of the rhizome of Curcuma wenyujin (WEZ) and establish a bioactive compounds-based holistic QC method. METHODS: The chemical profiling of the volatile oil (WVO) from 42 batches of WEZ collected from different growing areas was performed by GC-MS. The anti-lung cancer activity of different WVO samples was determined by CCK-8 assay against human lung cancer cells (A549). The apoptosis and cell cycle analysis under different concentrations of WVO were detected by flow cytometry. SIMCA-P software was used to perform multivariate statistical analysis on the chemical composition of different WVO samples and to find the different components. Active compounds were screened using a PLSR model of the spectrum-effect relationship. Bioactive compounds-based fingerprint and quantification of the leading bioactive compounds were developed by GC-MS and GC-FID, respectively. RESULTS: Seventy-eight compounds were detected in WVO and 54 were successfully identified. The multivariate statistical analysis uncovered that WVO components and the anti-A549 activity of WVO at the concentration of 60 nl/ml differ greatly according to the origin of the plant. The WVO at the concentration of 60 nl/ml (IC50) increased A549 cells apoptosis significantly with late and early apoptosis of 15.61% and 7.80%, and the number of cells in the G2/M phase were also increased significantly under this concentration. The spectrum-effect relationship analysis revealed that 44 compounds were positively correlated with their activities, and the result was verified by A549 cell viability assay. Sixteen positively correlated compounds were further selected as QC markers according to their relative amount > 0.5% and anticancer activity. Finally, the 16 QC markers-based GC-MS fingerprint was established to holistically control the quality of WEZ, and a GC-FID method was developed for the quantification of leading bioactive compounds, ß-elemene and ß-caryophyllene. CONCLUSION: Based on an anti-lung-cancer-guided spectrum-effect relationship approach, the bioactive compounds-based holistic QC method was successfully developed for WEZ, which could provide a valuable reference for the QC of TCMs.

The MYB transcription factor Baymax1 plays a critical role in rice male fertility.

Key message Rice male fertility gene Baymax1, isolated through map-based cloning, encodes a MYB transcription factor and is essential for rice tapetum and microspore development.Abstract The mining and characterization of male fertility gene will provide theoretical and material basis for future rice production. In Arabidopsis, the development of male organ (namely anther), usually involves the coordination between MYB (v-myb avian myeloblastosis viral oncogene homolog) and bHLH (basic helix-loop-helix) members. However, the role of MYB proteins in rice anther development remains poorly understood. In this study, we isolated and characterized a male sterile mutant (with normal vegetative growth) of Baymax1 (BM1), which encodes a MYB protein. The bm1 mutant exhibited slightly lagging meiosis, aborted transition of the tapetum to a secretory type, premature tapetal degeneration, and abnormal pollen exine formation, leading to ultimately lacks of visible pollens in the mature white anthers. Map-based cloning, complementation and targeted mutagenesis using CRISPR/Cas9 technology demonstrated that the mutated LOC_Os04g39470 is the causal gene in bm1. BM1 is preferentially expressed in rice anthers from stage 5 to stage 10. Phylogenetic analysis indicated that rice BM1 and its homologs in millet, maize, rape, cabbage, and pigeonpea are evolutionarily conserved. BM1 can physically interacts with bHLH protein TIP2, EAT1, and PHD (plant homeodomain)-finger member TIP3, respectively. Moreover, BM1 affects the expression of several known genes related to tapetum and microspore development. Collectively, our results suggest that BM1 is one of key regulators for rice male fertility and may serve as a potential target for rice male-sterile line breeding and hybrid seed production.

Application of intraoperative electrophysiological monitoring in vertebral canal decompression surgery for acute spinal cord injury.

OBJECTIVE: This study aimed to evaluate the joint monitoring of somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) in vertebral canal decompression surgery for acute spinal cord injury. METHODS: Twenty-four patients, who were admitted to the hospital for the surgical treatment of spinal cord injury with SEP and MEP monitoring, were assigned to the intraoperative monitoring group (group I). In addition, 24 patients who were admitted to the hospital for the surgical treatment of spinal cord injury without SEP or MEP monitoring were assigned to the control group (group C). RESULTS: In group I, there were significant changes before and after decompression surgery in the P40 latency and amplitude, and in the latency of MEP in the abductor hallucis brevis (AHB), in patients with improved spinal nerve function following surgery. In contrast, there were no significant differences in the P40 latency or amplitude, or the latency of MEP in the AHB, in patients who showed no improvement after surgery. CONCLUSION: In vertebral canal decompression surgery for acute spinal cord injury, the application of joint MEP and SEP monitoring can timely reflect changes in spinal cord function.

Efficacy of Indocyanine Green Fluorescence Angiography in Preventing Anastomotic Leakage After McKeown Minimally Invasive Esophagectomy.

BACKGROUND: Indocyanine green (ICG) fluorescence angiography (FA) was introduced to provide real-time intraoperative evaluation of the vascular perfusion of the gastric conduit during esophagectomy. However, its efficacy has not yet been proven. The aim of this study was to assess the usefulness of ICG-FA in the reduction of the rates of anastomotic leakage (AL) in McKeown minimally invasive esophagectomy (MIE). METHODS: From June 2017 to December 2019, patients aged between 18 and 80 years with esophageal carcinoma were enrolled in the study and each patient underwent McKeown MIE. Patients were divided into two groups, those with or without ICG-FA. The patient demographics and perioperative outcomes were comparable between the two groups. The primary outcome was the rate of AL. RESULTS: A total of 192 patients were included: 86 in the ICG-FA group and 106 in the non-ICG-FA group. Overall, 12 patients (6.3%) had AL; the rate of AL was 10.4% in the non-ICG-FA group, which was significantly higher than the 1.2% in the ICG-FA group. CONCLUSIONS: ICG-FA has the potential to reduce the rate of AL in McKeown MIE.