Harnessing Multistep Chalcogen Bonding Activation in the α-Stereoselective Synthesis of Iminoglycosides.

The use of noncovalent interactions (NCIs) has received significant attention as a pivotal synthetic handle. Recently, the exploitation of unconventional NCIs has gained considerable traction in challenging reaction manifolds such as glycosylation due to their capacity to facilitate entry into difficult-to-access sugars and glycomimetics. While investigations involving oxacyclic pyrano- or furanoside scaffolds are relatively common, methods that allow the selective synthesis of biologically important iminosugars are comparatively rare. Here, we report the capacity of a phosphonochalcogenide (PCH) to catalyze the stereoselective α-iminoglycosylation of iminoglycals with a wide array of glycosyl acceptors with remarkable protecting group tolerance. Mechanistic studies have illuminated the counterintuitive role of the catalyst in serially activating both the glycosyl donor and acceptor in the up/downstream stages of the reaction through chalcogen bonding (ChB). The dynamic interaction of chalcogens with substrates opens up new mechanistic opportunities based on iterative ChB catalyst engagement and disengagement in multiple elementary steps.

Inflammation mechanism and anti-inflammatory therapy of dry eye.

Dry eye is a widespread chronic inflammatory disease that causes fatigue, tingling, burning, and other symptoms. Dry eye is attributed to rheumatic diseases, diabetes, hormone disorders, and contact lenses, which activate inflammatory pathways: mitogen-activated protein kinases (MAPK) and nuclear factor-B (NF-κB), promote macrophage inflammatory cell and T cell activation, and inflammation factors. Clinicians use a combination of anti-inflammatory drugs to manage different symptoms of dry eye; some of these anti-inflammatory drugs are being developed. This review introduces the dry eye inflammation mechanisms and the involved inflammatory factors. We also elucidate the anti-inflammatory drug mechanism and the detection limits.

The Relationship between Complements and Age-Related Macular Degeneration and Its Pathogenesis.

Age-related macular degeneration is a retinal disease that causes permanent loss of central vision in people over the age of 65. Its pathogenesis may be related to mitochondrial dysfunction, inflammation, apoptosis, autophagy, complement, intestinal flora, and lipid disorders. In addition, the patient's genes, age, gender, cardiovascular disease, unhealthy diet, and living habits may also be risk factors for this disease. Complement proteins are widely distributed in serum and tissue fluid. In the early 21st century, a connection was found between the complement cascade and age-related macular degeneration. However, little is known about the effect of complement factors on the pathogenesis of age-related macular degeneration. This article reviews the factors associated with age-related macular degeneration, the relationship between each factor and complement, the related functions, and variants and provides new ideas for the treatment of this disease.

Prognostic value and gene regulatory network of CMSS1 in hepatocellular carcinoma.

BACKGROUND: Cms1 ribosomal small subunit homolog (CMSS1) is an RNA-binding protein that may play an important role in tumorigenesis and development. OBJECTIVE: RNA-seq data from the GEPIA database and the UALCAN database were used to analyze the expression of CMSS1 in liver hepatocellular carcinoma (LIHC) and its relationship with the clinicopathological features of the patients. METHODS: LinkedOmics was used to identify genes associated with CMSS1 expression and to identify miRNAs and transcription factors significantly associated with CMSS1 by GSEA. RESULTS: The expression level of CMSS1 in hepatocellular carcinoma tissues was significantly higher than that in normal tissues. In addition, the expression level of CMSS1 in advanced tumors was significantly higher than that in early tumors. The expression level of CMSS1 was higher in TP53-mutated tumors than in non-TP53-mutated tumors. CMSS1 expression levels were strongly correlated with disease-free survival (DFS) and overall survival (OS) in patients with LIHC, and high CMSS1 expression predicted poorer OS (P< 0.01) and DFS (P< 0.01). Meanwhile, our results suggested that CMSS1 is associated with the composition of the immune microenvironment of LIHC. CONCLUSIONS: The present study suggests that CMSS1 is a potential molecular marker for the diagnosis and prognostic of LIHC.

A synergistic Rh(I)/organoboron-catalysed site-selective carbohydrate functionalization that involves multiple stereocontrol.

Site-selective functionalization is a core synthetic strategy that has broad implications in organic synthesis. Particularly, exploiting chiral catalysis to control site selectivity in complex carbohydrate functionalizations has emerged as a leading method to unravel unprecedented routes into biologically relevant glycosides. However, robust catalytic systems available to overcome multiple facets of stereoselectivity challenges to this end still remain scarce. Here we report a synergistic chiral Rh(I)- and organoboron-catalysed protocol, which enables access into synthetically challenging but biologically relevant arylnaphthalene glycosides. Our method depicts the employment of chiral Rh(I) catalysis in site-selective carbohydrate functionalization and showcases the utility of boronic acid as a compatible co-catalyst. Crucial to the success of our method is the judicious choice of a suitable organoboron catalyst. We also determine that exquisite multiple aspects of stereocontrol, including enantio-, diastereo-, regio- and anomeric control and dynamic kinetic resolution, are concomitantly operative.

Establishment of gastric cancer organoid and its application in individualized therapy.

The application of cancer organoids is of great value in individualized therapy as an embodiment of the tumor of a patient, a gastric cancer organoid model was established and its application in individualized drug screening was explored. The primary tumor tissues of 3 patients with gastric cancer who underwent primary surgery at the Fourth Department of General Surgery of the First Hospital of Lanzhou University (Lanzhou, China) between July and August 2021 were selected and digested with mixed enzymes to prepare cell suspensions. Of these, two were cultured by mixing with Matrigel, while the cells from the third patient were placed in a 24-well ultra-low adhesion plate for suspension organoid culture. After intensive organoid growth, they were digested, passaged, cryopreserved and thawed for further analyses. The formation of gastric cancer organoids was observed under an inverted microscope. One case was selected, and organoids were compared with the original tumor tissue via H&E and immunohistochemical staining to evaluate the consistency of the two. Finally, paclitaxel, oxaliplatin and fluorouracil were administered to the organoids to verify the value of screening individualized drugs. It was indicated that the passage and cryopreservation of gastric cancer organoids were successfully established in all three cases. The H&E and immunohistochemical staining results suggested that the structure and protein expression of the organoids were highly similar to those of the source tumor tissue. The use of established gastric cancer organoids for individualized chemotherapy drug screening is of high clinical value. Gastric cancer organoids with high similarity to the original tissue may be successfully constructed by the suspension growth culture method. The established organoids may serve as an effective model for individualized drug screening.

A nomogram for decision-making assistance on surgical treatment of chronic osteomyelitis in long bones: Establishment and validation based on a retrospective multicenter cohort.

BACKGROUND: Chronic osteomyelitis remains a major challenge for orthopedic surgeons due to its high recurrence rate. Surgeons currently have few tools to estimate the likelihood of individual recurrence. We here aimed to develop a nomogram to better estimate individual recurrence rate after surgical treatment of chronic osteomyelitis in long bones. METHODS: We first retrospectively identified patients as training cohort who had received surgical treatment of chronic osteomyelitis in long bones between January 2010 and January 2016 from four hospitals. Patient demographic, microbiological, clinical, and therapeutic variables were collected and analyzed. Univariate and multivariate analyses were performed successively to identify independently predictive factors for recurrence. To reduce overfitting, the Bayesian information criterion was used to reduce variables in the original model. Nomograms were created with the reduced model after model selection. The nomogram was then internally validated with bootstrap resampling. We then further validated the performance of the established nomogram in validation cohort (data from two distinct institutions). RESULTS: Recurrence was found in 136 of 655 (20.8%) and 52 of 201 patients (25.9%) in training and validation cohorts respectively. We included six independent prognostic factors for recurrence in our prediction model: number of previous recurrences, epiphysial involvement, preoperative serum albumin level, axial length of the infectious lesion, lesion-removal method, and application of a muscular flap. After incorporating these six factors, the nomogram achieved good discrimination, with concordance indexes of 0.82 (95% CI, 0.79-0.85) and 0.80 (95% CI, 0.78-0.83) in predicting recurrence in the training and validation cohorts, respectively. Calibration curves were well fitted for both training and validation cohorts. CONCLUSIONS: Our nomogram achieved good preoperative prediction of recurrence in chronic osteomyelitis of long bones. Using this nomogram, the recurrence risk can be confidently predicted for each patient and treatment plan. After considering and discussing the functional prognosis with patients, physicians can establish a rational therapeutic plan. LEVEL OF EVIDENCE: Prognostic, Level III.

Dual gold/photoredox-catalyzed bis-arylative cyclization of chiral homopropargyl sulfonamides with diazonium salts: rapid access to enantioenriched 2,3-dihydropyrroles.

A novel dual gold/photoredox-catalyzed bis-arylative cyclization of chiral homopropargyl sulfonamides with diazonium salts has been developed, allowing the facile synthesis of various enantioenriched 2,3-dihydropyrroles in generally moderate to good yields with excellent enantioselectivities under very mild conditions without using any strong oxidants. The reaction is proposed to undergo an AuI/AuIII redox cycle promoted by visible-light photoredox catalysis.

Clinical evaluation of the Asian proximal femur intramedullary nail antirotation system (PFNA-II) for treatment of intertrochanteric fractures.

BACKGROUND: The preferred treatment of intertrochanteric fractures in aged patients is controversial. The purpose of the present study was to evaluate the outcomes of the Asian proximal femur intramedullary nail antirotation system (PFNA-II) for stabilization of such fractures. METHODS: The PFNA-II was used to treat intertrochanteric fractures in 163 elderly patients from March 2010 to March 2013. The patients comprised 69 men and 94 women with a mean age of 74.7 ± 13.0 years. All fractures were classified by the Orthopaedic Trauma Association classification system; 53, 83, and 27 fractures were classified as 31A1, 31A2, and 31A3, respectively. We statistically evaluated the intraoperative blood loss, operation time, incision length, X-ray exposure time, and postoperative outcomes. Patients were followed up for a mean of 15.2 months (range, 10-24 months). Functional outcomes were assessed according to the Harris hip scoring system. RESULTS: Statistical analysis revealed an average operation time of 45.7 min (range, 35-110 min), average intraoperative blood loss of 115.2 mL (range, 65-430 mL), X-ray exposure time of 2.7 ± 1.4 s (range, 2-6 s), and total incision length of 6.5 ± 2.2 cm (range, 5.5-13.0 cm). Patients were followed up for a mean of 14.5 months (range, 10-24 months). The neck shaft angle was 134° ± 15° (range, 115°-150°), and the fracture healing time was 14.0 ± 2.5 weeks (range, 11-19 weeks). The Harris hip score was 85.6 ± 17.5 points (range, 65-100 points) and included 41 excellent cases (25.15%), 92 good cases (56.44%), 26 moderate cases (15.95%), and 4 poor cases (2.45%) for a positive outcome rate of 81.60%. There were no varus hip deformities, screw cutouts, or femoral shaft fractures. Fourteen patients had thigh pain (9.82%), and five had inner thigh pain (3.07%); seven had more severe pain that was improved by physical therapy. CONCLUSION: PFNA-II has the advantages of a simple operation, few complications, and clinical efficacy for the treatment of intertrochanteric fractures. However, evaluation of its long-term efficacy and risk of other complications requires a large-sample, multicenter observational study.

[Impact of anxiety-depression symptoms on clinical recovery and serum TNF-alpha and IL-6 of patients with burns].

OBJECTIVE: To investigate the impact of anxiety-depression symptoms on the healing of burn wounds and the serum tumor necrosis factor a (TNF-alpha) and interleukin-6 (IL-6) in the patients with moderate and severe burns. METHODS: The patients with moderate and severe burns were divided into anxiety-depression group (24 patients) and non-anxiety-depression group (27 patients)according to the scores of anxiety-depression scores three days after burn measured by Hamilton Rating Scale for Depression (HAMD) and Hamilton Rating Scale for Anxiety (HAMA). The routine therapy was applied for both groups for 30 days. Then the scores of anxiety and depression and the degrees of wound healing were examined. The serum TNF-alpha IL-6 were measured with enzyme linked immunosorbent assay (ELISA). RESULTS: No significant decrease of the scores of depression was found before and after treatments in the anxiety-depression group (P > 0.05). The days that were needed for healing the wounds and the serum TNF-alpha and IL-6 increased in the patients with depression compared with the control group (P < 0.05). CONCLUSION: There are anxious and depressive reactions to burns by the patients. The continuous negative emotion can induce the increase of serum TNF-alpha and IL-6 and lead to delay of the healing of the burn wounds.

[Laboratory research of the influence of keyouling on the proliferation of human prepuce epidermis cells and condyloma acuminatum cells].

OBJECTIVE: To discuss the mechanism of the Chinese medicine Keyouling in the treatment of condyloma axuminatum (CA). METHODS: Human prepuce epidermis cells and CA cells were primarily cultured and subcultured. We determined the proliferation of human prepuce epidermis cells and CA cells, and observed the influence of Keyouling with different concentrations on the proliferation of human prepuce epidermis cells and CA cells by means of MTT colourimetry assay. RESULTS: The absorbance was directly proportional to the numbers of human prepuce epidermis cells (r = 0.9850, P < 0.001) and CA cells (r = 0.9892, P < 0.001). Keyouling had no effect on proliferation of the human prepuce epidermis cells, but it had significant inhibition on CA cells. The concentrations of Keyouling bore negative correlation with the proliferation percentage of CA cells(r = -0.4124, P < 0.01). CONCLUSION: Keyouling can significantly restrain the growth and proliferation of CA cells but has no damaging effect on normal organic cuticle cells. It is suggested that Keyouling might have anti-HPV effect.

[Experimental and clinical research on the effect of keyouling on condyloma acuminatum and adjustment of cellular immunity function].

OBJECTIVE: To discuss the mechanism of the traditional Chinese medicine Keyouling oral liquid in the treatment of condyloma acuminatum(CA) and the adjustment of cellular immunity function. METHODS: The IL-18 and TNF-alpha levels of peripheral serum and wart tissue of patterned rats and CA patients exposed to Keyouling were determined by means of double-antibody sandwich ELISA, and the NK cellular activity of the spleen of the patterned rats and that of the peripheral blood of the CA patients exposed to Keyouling were determined by means of 3H-TdR isotype release. RESULTS: The IL-18 and TNF-alpha levels, the NK cellular activity of the high-dosage group showed significant difference from those of the pattern group and low-dosage group in animal experiment(P < 0.05); the IL-18 and TNF-alpha levels of peripheral serum and wart tissues, and the NK cellular activity of the peripheral blood of the treatment group showed significant difference from those of the control group after treatment(P < 0.01, P < 0.05). CONCLUSIONS: Keyouling oral liquid has significant positive adjusting effect, which can markedly ameliorate the cellular immunadeficiency of the patterned animals and reinforce the cellular immunocompetence of CA patients.

[Experimental and clinical research of "Keyouling" on treatment of condyloma acuminata].

OBJECTIVE: To investigate the effects of traditional Chinese medicine "Keyouling" in treatment of condyloma acuminata (CA). METHODS: The effects of "Keyouling" at different concentrations on growth and proliferation of rabbits' prepuce epithelial cells and CA warts tissue were assessed by means of cellular primary culture and subculture, and the effects of "Keyouling" at different concentrations on the expression level of HPV6.11 DNA and expression level of HPV6.11 DNA of different area of CA patient's penis were quantitatively detected by means of FQ-PCR. RESULTS: "Keyouling" had no effect on growth and proliferation of rabbits' prepuce cuticle cells, but it had significant inhibition on CA warts tissue cells and expression of HPV6.11 DNA. Concentrations of "Keyouling" assumed negative correlated with cell proliferation rate of CA warts tissue and expression level of HPV6.11 DNA, and also had significant inhibition on expression of HPV6.11 DNA of negative cutaneous lesion area and cutaneous lesion area of CA patients. CONCLUSION: "Keyouling" had significant anti HPV6.11 effect, could significantly restrain growth and proliferation of CA warts tissue cells, while it had no damaging effect on normal organic cuticle cells. It was suggested that "Keyouling" was safe in clinical use and had good therapeutic effect on CA and subclinical infection.