[Research progress on processing history evolution, chemical constituents, and pharmacological action of Scorpio].

Scorpio is a valuable Chinese animal medicine commonly used in clinical practice in China. It is the main drug in the treatment of liver wind internal movement caused by various reasons throughout the history of traditional Chinese medicine(TCM), with the effects of relieving wind and spasm, dredging collaterals, relieving pain, and eliminating toxin and mass. Scorpio is poisonous and often used as medicine after processing. There are records of its processing as early as the Song Dynasty. Afterward, there were more than 15 processing methods, including frying with vinegar, neat processing, and stir-frying. After processing, the fishy smell could be removed to correct the taste, and the toxicity could be reduced, which was beneficial to clinical application. At present, the main reported components in Scorpio are protein polypeptides, alkaloids, and lipids, with many pharmacological effects, such as anti-cancer, anti-coagulation, anti-thrombosis, anti-atherosclerosis, and anti-bacteria. In this study, the historical evolution of processing, chemical constituents, and pharmacological action of Scorpio were discussed in order to provide references for the related research on Scorpio.

Effectiveness of Endoscopic Screening on Esophageal Cancer Incidence and Mortality: A 9-Year Report of the Endoscopic Screening for Esophageal Cancer in China (ESECC) Randomized Trial.

PURPOSE: To evaluate the effectiveness of endoscopic screening against incidence of and mortality from esophageal squamous cell carcinoma (ESCC). METHODS: From January 2012 to September 2016, we conducted a community-based cluster randomized controlled trial involving permanent residents age 45-69 years in a high-risk region for ESCC in northern China. A total of 668 targeted villages were randomly assigned in a 1:1 ratio to the screening group (offered Lugol's chromoendoscopy) or control group (no screening). Intention-to-treat and per-protocol analyses were performed to compare esophageal cancer (EC) incidence and mortality between the two groups. The per-protocol analysis adjusted for nonadherence to the screening procedure. RESULTS: A total of 33,847 participants were included in the analysis: 17,104 in the screening group, 15,165 (88.7%) of whom underwent screening, and 16,743 in the control group. During a maximum follow-up of 9 years, EC incidence in the screening and control groups were 60.9 and 72.5 per 100,000 person-years, respectively; mortality in the screening and control groups were 29.7 and 32.4 per 100,000 person-years, respectively. Compared with the control group, the incidence and mortality of the screening group reduced by 19% (adjusted hazard ratio [aHR], 0.81 [95% CI, 0.60 to 1.09]) and 18% (aHR, 0.82 [95% CI, 0.53 to 1.26]), respectively, in the intention-to-treat analysis; and by 22% (aHR, 0.78 [95% CI, 0.56 to 1.10]) and 21% (aHR, 0.79 [95% CI, 0.49 to 1.30]), respectively, in the per-protocol analysis. CONCLUSION: With a 9-year follow-up, our trial suggests that chromoendoscopic screening induces modest reductions in EC incidence and mortality. A more efficient strategy for EC screening and subsequent patient management should be established to guarantee the effectiveness of endoscopic screening.

First Report of Colletotrichum siamense Causing Fruit Anthracnose on Pomegranate (Punica granatum) in China.

As a native crop in central Asia, pomegranate (Punica granatum L.) has been cultivated in China for more than 2000 years (Yuan et al. 2007). In August 2022, typical symptoms of anthracnose were observed on pomegranate fruitlets in the main cultivation area (34°22'36″N, 109°15'58″E) in Shaanxi Province, China. The disease incidence was approximately 10 to 15% in the field. The initial symptoms were slightly small, light, dark, sunken lesions with irregular, circular shapes. As the disease progressed, the necrotic lesions gradually expanded and merged, eventually leading to the abscission of fruits (Figure 1, A). The symptomatic lesion samples of the pomegranate were sterilized for 1.5 min in 75% ethanol and 2 min in 1% NaClO and rinsed for 2 min in sterile water three times. The sterilized samples were dried on sterile filter paper and placed on potato dextrose agar (PDA) media at 25 ℃ for 5 days. The mycelia of the isolate were white, cottony, and diffuse (Figure 1, B and C). The conidia were single-celled, smooth, aseptate, and cylindrical with slightly rounded ends, measured 13.5 to 17.5 µm long and 3.5 to 6.5 µm wide (mean 16.0 × 4.5 µm, n = 50) (Figure 1, D). These morphological characteristics were identical to those of Colletotrichum siamense (Weir et al. 2012; Cannon et al. 2012; Zhuo et al. 2022). For accurate molecular characterization of the fungus, genomic DNA was extracted from the hyphae of the two isolates using microorganism lysis buffer (Takara, Japan). The internal transcribed spacer (ITS), calmodulin (CAL), actin (ACT), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and beta-tubulin (TUB2) regions were amplified and sequenced. All the sequences were submitted to GenBank with accession numbers OQ832556 (ITS), OQ848589 (GAPDH), OQ848590 (ACT), OQ848591 (CAL), and OQ986593 (TUB2). The isolates showed 99 to 100% identity with sequences of Colletotrichum siamense (100% with GAPDH, ACT, CAL, and TUB2; 99.81% with ITS). The morphology of the strain was studied, and multilocus (ITS, GAPDH, ACT, CAL, and TUB2) phylogenetic analysis was performed (Figure 2). Therefore, the causal pathogen was identified as C. siamense based on the results of morphological and molecular analyses. Pathogenicity assays were performed on pomegranate (cv. Lishanhong) fruits. A conidial suspension (1×106 conidia/mL) was sprayed onto 10 unwounded fruits to inoculate them as infected samples, and the controls were inoculated with a sterile water suspension. All the samples were maintained in an artificial climate box at 25 ± 2 ℃ with 70% relative humidity, and the photoperiod was set as 12:12 light:dark. After 5 to 7 days, anthracnose symptoms developed on the surface of the inoculated fruit, whereas the control fruits remained healthy. The diseased fruits exhibited brown necrotic lesions, whereas the upper surfaces of the control fruits remained asymptomatic. The morphological and molecular characteristics of the reisolated pathogen were identical to those of the original fungus isolated from the natural fruit. C. siamense has been reported to cause anthracnose in the southeastern United States (Xavier et al. 2019). The pathogen causing anthracnose on pomegranates has been reported to be Colletotrichum fructicola in China (Hu et al. 2023). To our knowledge, this is the first report of anthracnose on pomegranate fruits caused by C. siamense in China. This disease can directly affect the quality and yield of the fruit. Thus, information about the characteristics of this disease could provide a theoretical basis for its prevention and control.

FGF17 protects cerebral ischemia reperfusion-induced blood-brain barrier disruption via FGF receptor 3-mediated PI3K/AKT signaling pathway.

Maintaining blood-brain barrier (BBB) integrity is critical components of therapeutic approach for ischemic stroke. Fibroblast growth factor 17 (FGF17), a member of FGF8 superfamily, exhibits the strongest expression throughout the wall of all major arteries during development. However, its molecular action and potential protective role on brain endothelial cells after stroke remains unclear. Here, we observed reduced levels of FGF17 in the serum of patients with ischemic stroke, as well as in the brains of mice subjected to middle cerebral artery occlusion (MCAO) injury and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced brain microvascular endothelial cells (bEnd.3) cells. Moreover, treatment with exogenous recombinant human FGF17 (rhFGF17) decreased infarct volume, improved neurological deficits, reduced Evans Blue leakage and upregulated the expression of tight junctions in MCAO-injured mice. Meanwhile, rhFGF17 increased cell viability, enhanced trans-endothelial electrical resistance, reduced sodium fluorescein leakage, and alleviated reactive oxygen species (ROS) generation in OGD/R-induced bEnd.3 cells. Mechanistically, the treatment with rhFGF17 resulted in nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear accumulation and upregulation of heme oxygenase-1 (HO-1) expression. Additionally, based on in-vivo and in-vitro research, rhFGF17 exerted protective effects against ischemia/reperfusion (I/R) -induced BBB disruption and endothelial cell apoptosis through the activation of the FGF receptor 3/PI3K/AKT signaling pathway. Overall, our findings indicated that FGF17 may hold promise as a novel therapeutic strategy for ischemic stroke patients.

Development and external validation of a quantitative diagnostic model for malignant gastric lesions in clinical opportunistic screening: A multicenter real-world study.

BACKGROUND: Clinical opportunistic screening is a cost-effective cancer screening modality. This study aimed to establish an easy-to-use diagnostic model serving as a risk stratification tool for identification of individuals with malignant gastric lesions for opportunistic screening. METHODS: We developed a questionnaire-based diagnostic model using a joint dataset including two clinical cohorts from northern and southern China. The cohorts consisted of 17,360 outpatients who had undergone upper gastrointestinal endoscopic examination in endoscopic clinics. The final model was derived based on unconditional logistic regression, and predictors were selected according to the Akaike information criterion. External validation was carried out with 32,614 participants from a community-based randomized controlled trial. RESULTS: This questionnaire-based diagnostic model for malignant gastric lesions had eight predictors, including advanced age, male gender, family history of gastric cancer, low body mass index, unexplained weight loss, consumption of leftover food, consumption of preserved food, and epigastric pain. This model showed high discriminative power in the development set with an area under the receiver operating characteristic curve (AUC) of 0.791 (95% confidence interval [CI]: 0.750-0.831). External validation of the model in the general population generated an AUC of 0.696 (95% CI: 0.570-0.822). This model showed an ideal ability for enriching prevalent malignant gastric lesions when applied to various scenarios. CONCLUSION: This easy-to-use questionnaire-based model for diagnosis of prevalent malignant gastric lesions may serve as an effective prescreening tool in clinical opportunistic screening for gastric cancer.

Experimental Study on the Diffusion Law of Coal-Based Solid Waste Slurry with Grouting Filling in the Gangue Voids of the Caving Zone.

Due to the concealment of the caving zone, it is difficult to detect and grasp the diffusion law of the slurry in the voids of the gangue pile. On the preparation of reasonable grouting filling materials, a large-scale three-dimensional gangue grouting filling test system has been established to detect the slurry pressure and resistivity inside the gangue pile and analyze the flow pattern of the slurry in the voids of the gangue pile. The research results show that the slump and bleeding rate of the filling slurry are significantly reduced with the increase of the fly ash content. The optimal ratio of fly ash, coal gangue, and gasification slag is 7:2:1, with a mass fraction of 72%. In the process of grouting, the internal pressure of the gangue pile can be divided into the initial stable stage, the step growth stage, and the pressure stability stage, and the change curve of the pressure sensor at the lower level is similar. The resistance value of the original broken gangue in the experiment is approximately 1600 Ω. Grouting filling forms a slurry-rock mixture, and its resistance continuously decreases with the stable injection of the slurry (minimum value 150 Ω). It is determined that the slurry near the grouting hole mainly diffuses longitudinally with a good void filling effect. The void channels of slurry diffusion are randomly distributed and have different shapes, which hinder slurry flow and diffusion. Slurry particles accumulate and settle at local small voids. Meanwhile, the surface of the gangue blocks is dry, and the slurry absorbs part of the water during diffusion, resulting in the increase of the slurry concentration and the weakening of the lateral diffusion ability. Secondary or multiple grouting can effectively fill the void of the broken gangue and further improve the filling effect.

The effect and mechanism of low-molecular-weight heparin on the decidualization of stromal cells in early pregnancy.

OBJECTIVE: This study aimed to analyze the effect of low-molecular-weight heparin (LMWH) on the decidualization of stromal cells in early pregnancy and explore the effect of LMWH on pregnancy outcomes. METHODS: Recurrent spontaneous abortion (RSA) mouse model (CBA/J × DBA/2) and normal pregnant mouse model (CBA/J × BALB/c) were established. The female mice were checked for a mucus plug twice daily to identify a potential pregnancy. When a mucus plug was found, conception was considered to have occurred 12 h previously. The pregnant mice were divided randomly into a normal pregnancy control group, an RSA model group, and an RSA + LMWH experimental group (n = 10 mice in each group). Halfway through the 12th day of pregnancy, the embryonic loss of the mice was observed; a real-time quantitative polymerase chain reaction was used to detect the messenger ribonucleic acid (mRNA) expressions of prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1) in the decidua of the mice. Additionally, the decidual tissues of patients with RSA and those of normal women in early pregnancy who required artificial abortion were collected and divided into an RSA group and a control group. Decidual stromal cells were isolated and cultured to compare cell proliferation between the two groups, and cellular migration and invasion were detected by membrane stromal cells. Western blotting was used to detect the protein expressions of proliferating cell nuclear antigen (PCNA), cyclin D1, matrix metalloproteinase- (MMP) 2, and MMP-7 in stromal cells treated with LMWH. RESULTS: Compared with the RSA group, LMWH significantly reduced the pregnancy loss rate in the RSA mice (p < 0.05). Compared with the RSA group, the LMWH + RSA group had significantly higher expression levels of PRL and IGFBP1 mRNA (p < 0.01). LMWH promoted the proliferation, migration, and invasion of human decidual stromal cells; compared with the control group, the expression levels of MMP-2, MMP-7, cyclin D1, and PCNA proteins in the decidual stromal cells of the LMWH group increased (p < 0.05). CONCLUSIONS: The use of LMWH can improve pregnancy outcomes by enhancing the proliferation and migration of stromal cells in early pregnancy and the decidualization of stromal cells.

Surgical quality determines the long-term survival superiority of right over left thoracic esophagectomy for localized esophageal squamous cell carcinoma patients: a real-world multicenter study.

OBJECTIVE: The objective was to compare the long-term overall survival (OS) of right versus left thoracic esophagectomy, and to evaluate whether surgical quality impacts comparison result. BACKGROUND: Controversy regarding the optimal thoracic esophagectomy approach persists for esophageal squamous cell carcinoma (ESCC). No study has assessed the effect of surgical quality in comparison between right and left approaches. METHODS: The authors consecutively recruited 5556 operable ESCC patients from two high-volume centers in China, of whom 2220 and 3336 received right and left thoracic esophagectomy, respectively. Cumulative sum was used to evaluate the learning curve for operation time of right approach, as the indicator of surgical proficiency. RESULTS: With a median follow-up of 83.1 months, right approach, harvesting more lymph nodes, tended to have a better OS than left approach (Mean: 23.8 vs. 16.7 nodes; adjusted hazard ratio (HR)=0.93, 95% CI: 0.85-1.02). Subset analysis by the extent of lymphadenectomy demonstrated that right approach with adequate lymphadenectomy (≥15 nodes) resulted in statistically significant OS benefit compared with left approach (adjusted HR=0.86, 95% CI: 0.77-0.95), but not with limited lymphadenectomy. Subset analysis by surgical proficiency showed that proficient right approach conferred a better OS than left approach (adjusted HR=0.75, 95% CI: 0.64-0.88), but improficient right approach did not have such survival advantage. CONCLUSIONS: Surgical quality plays a crucial role in survival comparison between surgical procedures. Right thoracic esophagectomy performed with adequate lymphadenectomy and surgical proficiency, conferring more favorable survival than left approach, should be recommended as the preferred surgical procedure for localized ESCC.

Endoscopic management of duodenal perforation caused by foreign bodies in adults: A retrospective study.

BACKGROUND AND AIMS: Duodenal perforation caused by foreign bodies (FBs) is very rare but is an urgent emergency that traditionally requires surgical intervention. Several case reports have reported the successful endoscopic removal of duodenal perforating FBs. Here we aimed to evaluate the safety and efficacy of endoscopic management of duodenal perforating FBs in adults. METHODS: Between October 2004 and October 2022, 12,851 patients with endoscopically diagnosed gastrointestinal FBs from four tertiary hospitals in China were retrospectively reviewed. Patients were enrolled if they were endoscopically and/or radiographically diagnosed with duodenal perforating FBs. RESULTS: The incidence of duodenal total FBs and perforating FBs was 1.9% and 0.3%, respectively. Thirty-four patients were enrolled. Endoscopic removal was achieved in 25 patients (73.5%), and nine patients (26.5%) received surgery. For the endoscopic group, most perforating FBs were located in the duodenal bulb (36.0%) and descending part (28.0%). The adverse events included 3 mucosal injuries and 1 localized peritonitis. All patients were cured after conventional treatment. In the surgical group, most FBs were lodged in the descending part (55.6%). One patient developed localized peritonitis and one patient died of multiple organ failure. The significant features of FBs requiring surgery included FB over 10 cm, both sides perforation, multiple perforating FBs and massive pus overflow. CONCLUSION: Endoscopic removal of duodenal perforating FBs is safe and effective, and can be the first choice of treatment for experienced endoscopists. Surgical intervention may be required for patients with FBs over 10 cm, both sides perforation, multiple perforating FBs, or severe infections.

Brucine suppresses proliferation and promotes apoptosis of human cholangiacarcinoma cells via the inhibition of COX2 expression.

Aims The aim of this study was to investigate the anti-tumor efficacy of brucine on intrahepatic cholangiocarcinoma (ICC). Methods ICC QBC939 cells were treated with brucine, cell viability, cell cycle and apoptosis were analyzed using CCK-8 and flow cytometry. The expression of COX-2 and apoptosis related proteins Casp3, Bax and Bcl-2 were detected by Western blot analysis. QBC939 cells were subcutaneously transplanted into nude mice and the mice were injected with brucine intraperitoneally. The expression of Ki67, COX-2 and apoptosis related proteins were detected by immunohistochemical staining and Western blot analysis. Results Brucine significantly inhibited the proliferation and cell cycle progression while promoted the apoptosis of QBC939 cells. The expression of the apoptotic proteins Casp3 and Bax was upregulated, while the expression of Bcl-2 and COX-2 was downregulated in QBC939 cells with brucine treatment. Moreover, the overexpression of COX-2 could antagonize the effects of brucine on QBC939 cells. In vivo, brucine inhibited subcutaneous tumor formation in nude mice, and the expression of Ki67, COX-2 and Bcl-2 decreased while the expression of Casp3 and Bax increased in tumor tissues from nude mice with brucine treatment. Conclusions Brucine can significantly inhibit the progression of cholangiocarcinoma in vitro and in vivo, and the mechanism may be related to the inhibition of COX-2 expression.

Postoperative serum squamous cell carcinoma antigen and carcinoembryonic antigen predict overall survival in surgical patients with esophageal squamous cell carcinoma.

Background: Tumor markers are routinely used in clinical practice. However, for resectable patients with esophageal squamous cell carcinoma (ESCC), they are applied infrequently as their prognostic significance is incompletely understood. Methods: This historical cohort study included 2769 patients with resected ESCC from 2011 to 2018 in a high-risk area in northern China. Their clinical data were extracted from the Electronic Medical Record. Survival analysis of eight common tumor markers was performed with multivariable Cox proportional hazards regressions. Results: With a median follow-up of 39.5 months, 901 deaths occurred. Among the eight target markers, elevated postoperative serum SCC (Squamous cell carcinoma antigen) and CEA (Carcinoembryonic antigen) predicted poor overall survival (SCC HRadjusted: 2.67, 95% CI: 1.70-4.17; CEA HRadjusted: 2.36, 95% CI: 1.14-4.86). In contrast, preoperative levels were not significantly associated with survival. Stratified analysis also demonstrated poorer survival in seropositive groups of postoperative SCC and CEA within each TNM stage. The above associations were generally robust using different quantiles of concentrations above the upper limit of the clinical normal range as alternative cutoffs. Regarding temporal trends of serum levels, SCC and CEA were similar. Their concentrations fell rapidly after surgery and thereafter remained relatively stable. Conclusion: Postoperative serum SCC and CEA levels predict the overall survival of ESCC surgical patients. More importance should be attached to the use of these markers in clinical applications.

Microfluidic integrated D-shaped optical fiber SERS probe with high sensitivity and ability of multi-molecule detection.

In order to enhance the sensitivity, integration, and practical application capability of Raman detection systems, we propose a multi-channel microfluidic integrated D-shaped optical fiber SERS (Surface-enhanced Raman scattering) probe structure. Firstly, a microfluidic polydimethylsiloxane (PDMS) channel was fabricated using a self-designed multi-channel microfluidic template. Secondly, a uniform layer of silver nanoparticles was deposited on the D-shaped optical fiber using the liquid-liquid interface method. Finally, the D-shaped optical fiber was plasma-bonded to the multi-channel microfluidic channel and a cover glass, resulting in a microfluidic integrated D-shaped optical fiber SERS probe. The prepared sample exhibited excellent detection performance for R6G (rhodamine 6 G) with a detection limit as low as 10-11 mol/L and an enhancement factor of 1.14 × 109. Moreover, the multi-channel configuration enables simultaneous detection of multiple molecules, demonstrating excellent multi-channel multiplexing capability.

Lugol-unstained lesions location in the esophagus affects the detection rate of malignancy: a population-based study.

INTRODUCTION: This study aimed to evaluate the impact of Lugol-unstained lesion (LUL) location on the detection yield, which may help the endoscopist select targets for biopsy. METHODS: We enrolled 1064 subjects who had LULs at the baseline screening of a population-based randomized controlled trial. There were 1166 LULs with recorded location and pathologic diagnosis, and these were used for analysis. The detection rate of severe dysplasia and above (SDA) was calculated as the number of LULs identified as SDA divided by the number of LULs biopsied. Logistic regression with a generalized estimating equation was applied to evaluate the association between the location of a given LUL and the risk of the LUL being SDA. RESULTS: The detection rate of SDA for LULs located in the lower, middle, and upper esophagus increased from 5.9% and 10.9% to 16.7%. LUL location was significantly associated with having SDA (adjusted odds ratio (OR)upper vs. lower  = 2.88, 95% confidential interval (CI) = 1.48-5.60; adjusted ORmiddle vs. lower  = 1.63, 95% CI = 0.96-2.76), and the association was stronger in subgroups with a family history of esophageal squamous cell carcinoma (ESCC) (adjusted ORupper vs. lower  = 9.72, 95% CI = 2.57-36.69; adjusted ORmiddle vs. lower  = 3.76, 95% CI = 0.93-15.21). CONCLUSIONS: Our results suggest that more attention should be paid by endoscopists to LULs in the upper and middle esophagus, particularly for individuals with a family history of ESCC.

How should extra-large Lugol-unstained lesions of the esophagus be treated? Results from a population-based cohort study.

BACKGROUND: Current guidelines recommend only severe dysplasia and above (SDA) lesions of the esophageal squamous epithelium for clinical intervention. However, the histopathologic diagnosis derived from tissue biopsies may be subject to underestimation of severity. METHODS: 1073 participants from whom biopsies were taken at baseline chromoendoscopic examination in a population-based screening trial were enrolled in this study. The size of the Lugol-unstained lesions (LULs) was mainly analyzed. The outcome was defined as SDA lesions either identified at baseline screening, or during follow-up, collectively referred to as the cumulative risk of SDA. Multivariable logistic regression models were used to evaluate the cumulative risk of SDA. RESULTS: One hundred and forty-six SDA cases were identified in the study period. Participants with large LULs had a high cumulative incidence of SDA (cumulative incidence16-20mm : 55.88%; cumulative incidence>20mm : 76.92%) in the median of 7-year duration. LULs of large size were significantly associated with a higher cumulative risk of SDA, regardless of the pathologic diagnosis (adjusted OR16-20mmvs.≤5mm = 21.02, 95% CI: 7.56-58.47; adjusted OR>20mmvs.≤5mm = 33.62, 95% CI: 11.79-95.87). CONCLUSIONS: Results from this study suggest physician-patient shared decision-making regarding clinical treatment or intensive surveillance should be carried out for LULs >20 mm in the esophagus, regardless of the histologic diagnosis. For those with LULs of 16-20 mm, intensive surveillance would also best be considered.

Absence of Lugol staining indicates initiation of esophageal squamous cell carcinoma: A combined genomic and epidemiologic study.

The genomic characteristics during the carcinogenic process of esophageal squamous cell carcinoma (ESCC) remain largely unknown. We report here the genomic characteristics of 106 esophageal tissues of various stages from a population-based screening cohort in China ("Endoscopic Screening for Esophageal Cancer in China" trial) and 57 ESCC tissues from a local hospital. A significant increase in somatic mutation and copy number alterations is observed in the non-dysplastic Lugol unstaining lesions (ND-LULs). Extensive clonal expansion has emerged in the ND-LULs to an extent similar to that in higher-stage lesions. The burden of genomic alterations correlates with the size of LULs in the ND-LULs. 8-year follow-up shows that ND-LULs harbor an increased risk of progression to ESCC (adjusted IRR6-10 mm vs. none = 4.66, adjusted IRR>10 mm vs. none = 40.70), and the risk is correlated with LUL size for both non-dysplastic and dysplastic lesions. Lugol unstaining can be the initial stage in the carcinogenic process of ESCC.

Rh(I)-Catalyzed [5 + 2]/[2 + 2] Cycloaddition Cascade to Access a Cyclobutane-Fused [4-5-6-7] Tetracyclic Framework.

A Rh(I)-catalyzed [5 + 2]/[2 + 2] cycloaddition cascade has been developed to afford a complex and highly strained [4-5-6-7] tetracyclic framework in good yields and excellent diastereoselectivities. During this transformation, three rings, three C-C bonds, and four contiguous stereocenters were formed efficiently. Mechanistically, the rare sterically congested multisubstituted cyclobutanes are constructed readily through Michael addition and a Mannich reaction cascade.

Clinical outcomes of implantation of posterior chamber phakic intraocular lens for pathologic and non-pathologic myopia.

BACKGROUND: To compare the clinical outcomes of posterior chamber phakic intraocular lens (pIOL) implantation for non-pathological myopia and pathological myopia. METHODS: This retrospective case series study which were conducted in Beijing Tongren Eye Center between July 2017 and Oct 2021 comprised 192 eyes of 100 consecutive patients undergoing pIOL implantation. Eyes were divided into two groups based on having pathological myopia or not. Predictability, efficacy, safety, and adverse events were compared at 6 months after pIOL implantation. RESULTS: Our study included 86 non-pathological myopes (171 eyes, group1) and 14 pathological myopes (21eyes, group2) to analysis. The average ages were 25.5 and 33.0, respectively, and the spherical equivalent (SE) were -9.31D and -17.50D pre-operation. Six months after pIOL implantation, the SE were 0.00 and -0.50, respectively, and the refraction changes were statistically significant (P ≤ 0.05). Six months after surgery, 76.92% and 80.41% were within ± 0.50 D of the target and 92.31% and 95.88% were within ± 1.00 D. All eyes had unchanged BCVA or gained 1 or more lines in both groups and mean BCVA both improved a line 6m after operation. The efficacy index in the two groups were 0.95 and 0.88 and the safety index were 1.20, 1.33, respectively which was significantly different (P ≤ 0.05). Over the 6-month follow-up, no cataract, pigment dispersion glaucoma, pupillary block, or other vision-threatening complications happened, either. CONCLUSIONS: The pIOL performed well for the correction of both non-pathological and pathological myopia throughout the 6-month observation period. The clinical outcomes of pIOL implantation for non-pathological myopia are essentially equivalent to those for pathological myopia.

Risk factors and survival analysis of haemodialysis complicated with infective endocarditis.

The clinical features and risk factors for survival time were analysed in haemodialysis patients complicated with infective endocarditis. A total of 101 infective endocarditis (IE) patients treated at Hangzhou First People's Hospital, from January 1, 2012, to April 1, 2022, were included in the present study. Baseline demographic data and laboratory data were collected for statistical analysis of risk factors and survival time in the IE with haemodialysis group (HD-IE group, n=15) and the IE without haemodialysis group (NHD-IE group, n=86). Haemoglobin, red blood cells, C-reactive protein, procalcitonin, serum albumin, diabetes, invasive procedures, positive blood bacteria culture, heart valve calcification ratio, and left ventricular ejection fraction level were risk factors for infective endocarditis complicated with haemodialysis (P<0.05). Compared with the NHD-IE group, the HD-IE group had an obviously increased risk of mortality (χ2=6.323, P=0.012). The univariate Cox regression analysis showed that age, haemoglobin, red blood cells, serum albumin, left ventricular ejection score, longest vegetation diameter, combined hypotension and diabetes were risk factors for death; furthermore, multivariate Cox regression showed that age (HR=1.187, P=0.015), combined hypotension (HR=0.921, P=0.025) and the longest vegetation diameter (HR=9.191, P=0.004) were independent risk factors affecting the survival of patients. Collectively, the present study revealed that the mortality rate of HD-IE patients was higher than that of NHD-IE patients. Older age, hypotension, and the longest vegetation diameter were independent risk factors affecting the survival of patients. For HD-IE patients, active and effective antibiotic treatment or surgical treatment should be strongly recommended.

Hierarchical neural network with efficient selection inference.

The image classification precision is vastly enhanced with the growing complexity of convolutional neural network (CNN) structures. However, the uneven visual separability between categories leads to various difficulties in classification. The hierarchical structure of categories can be leveraged to deal with it, but a few CNNs pay attention to the character of data. Besides, a network model with a hierarchical structure is promising to extract more specific features from the data than current CNNs, since, for the latter, all categories have the same fixed number of layers for feed-forward computation. In this paper, we propose to use category hierarchies to integrate ResNet-style modules to form a hierarchical network model in a top-down manner. To extract abundant discriminative features and improve the computation efficiency, we adopt residual block selection based on coarse categories to allocate different computation paths. Each residual block works as a switch to determine the JUMP or JOIN mode for an individual coarse category. Interestingly, since some categories need less feed-forward computation than others by jumping layers, the average inference time cost is reduced. Extensive experiments show that our hierarchical network achieves higher prediction accuracy with similar FLOPs on CIFAR-10 and CIFAR-100, SVHM, and Tiny-ImageNet datasets compared to original residual networks and other existing selection inference methods.

A prognostic model incorporating inflammatory cells and cytokines for newly diagnosed multiple myeloma patients.

Peripheral blood cell counts and cytokines can be used as predictors of multiple myeloma (MM) patients' outcomes. 313 newly diagnosed MM patients treated with novel agents were divided into training and validation cohorts. We selected the common peripheral blood cell counts, including the lymphocyte/monocyte ratio (LMR), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR), systemic inflammation response index (SIRI), and serum cytokines which contained tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-2 receptor (IL-2R), interleukin-8 (IL-8), interleukin-6 (IL-6), and interleukin-10 (IL-10) as related variables. The least absolute shrinkage and selection operator (LASSO) regression was conducted to sort the predictor variables in the training cohort, and then the developed nomogram was assessed in the training and validation cohort. Our study showed that SIRI, PLR, and IL-8 were independent prognostic factors for the survival of MM patients. Patients with lower SIRI (≤ 0.87) had superior survival than patients with higher SIRI (> 0.87). Further, according to the LASSO regression, a nomogram embracing LMR (> 3.78), SIRI (> 0.87), PLR (≤ 106.44), and IL-8 was established. The nomogram demonstrated a better correlation with the outcomes of MM patients in the training cohort than International Staging System (ISS) and Revised-International Staging System (R-ISS). The same results were verified in the validation cohort. The nomogram incorporating inflammatory cells and cytokines could be a helpful tool to stratify MM patients in the era of novel agents.