Understanding formation processes of calcareous nephrolithiasis in renal interstitium and tubule lumen.

Kidney stone, one of the oldest known diseases, has plagued humans for centuries, consistently imposing a heavy burden on patients and healthcare systems worldwide due to their high incidence and recurrence rates. Advancements in endoscopy, imaging, genetics, molecular biology and bioinformatics have led to a deeper and more comprehensive understanding of the mechanism behind nephrolithiasis. Kidney stone formation is a complex, multi-step and long-term process involving the transformation of stone-forming salts from free ions into asymptomatic or symptomatic stones influenced by physical, chemical and biological factors. Among the various types of kidney stones observed in clinical practice, calcareous nephrolithiasis is currently the most common and exhibits the most intricate formation mechanism. Extensive research suggests that calcareous nephrolithiasis primarily originates from interstitial subepithelial calcified plaques and/or calcified blockages in the openings of collecting ducts. These calcified plaques and blockages eventually come into contact with urine in the renal pelvis, serving as a nidus for crystal formation and subsequent stone growth. Both pathways of stone formation share similar mechanisms, such as the drive of abnormal urine composition, involvement of oxidative stress and inflammation, and an imbalance of stone inhibitors and promoters. However, they also possess unique characteristics. Hence, this review aims to provide detailed description and present recent discoveries regarding the formation processes of calcareous nephrolithiasis from two distinct birthplaces: renal interstitium and tubule lumen.

Synthesis of Fully Substituted Difluoromethylpyrazoles by Cyclization of Difluoroacetohydrazonoyl Bromides with 2-Acylacetonitriles or Malononitrile.

A concise and efficient method for the construction of fully substituted difluoromethylpyrazoles is achieved by a cyclization reaction between difluoroacetohydrazonoyl bromides and 2-acylacetonitrile or malononitrile. The method features advantages such as mild reaction conditions, broad substrate scope, good product yields, and high regioselectivity.

[3 + 2] Cycloaddition Reaction of Vinylsulfonium Salts with Hydrazonoyl Halides: Synthesis of Pyrazoles.

An efficient [3 + 2] cycloaddition reaction between in situ generated nitrile imines from hydrazonoyl halides and vinylsulfonium salts is developed. The nitrile imines are demonstrated to be a new class of reaction partner for vinylsulfonium salts to conduct the [3 + 2] cycloaddition reaction. The process provides a concise and efficient method for the construction of pyrazole derivatives under mild reaction conditions with broad substrate scope, good product yields, and high regioselectivity.

Synthesis of difluoromethylated spiropyrazolones via [3 + 2] cycloaddition of difluoroacetohydrazonoyl bromides with alkylidene pyrazolones.

An effective [3 + 2] cycloaddition reaction of difluoromethyl or trifluoromethyl hydrazonoyl bromides with alkylidene pyrazolones was disclosed. This method provides an efficient approach for accessing a variety of highly functionalized fluoroalkyl spiropyrazolones in good yields. This protocol also features some advantages such as easily available and stable substrates, simple operation procedures, and atom and step economy. The formation of (cis)- and (trans)-products was discussed.

Intravenous immunoglobulin for treatment of hospitalized COVID-19 patients: an evidence mapping and meta-analysis.

BACKGROUND: The clinical efficacy and safety of intravenous immunoglobulin (IVIg) treatment for COVID-19 remain controversial. This study aimed to map the current status and gaps of available evidence, and conduct a meta-analysis to further investigate the benefit of IVIg in COVID-19 patients. METHODS: Electronic databases were searched for systematic reviews/meta-analyses (SR/MAs), primary studies with control groups, reporting on the use of IVIg in patients with COVID-19. A random-effects meta-analysis with subgroup analyses regarding study design and patient disease severity was performed. Our outcomes of interest determined by the evidence mapping, were mortality, length of hospitalization (days), length of intensive care unit (ICU) stay (days), number of patients requiring mechanical ventilation, and adverse events. RESULTS: We included 34 studies (12 SR/MAs, 8 prospective and 14 retrospective studies). A total of 5571 hospitalized patients were involved in 22 primary studies. Random-effects meta-analyses of very low to moderate evidence showed that there was little or no difference between IVIg and standard care or placebo in reducing mortality (relative risk [RR] 0.91; 95% CI 0.78-1.06; risk difference [RD] 3.3% fewer), length of hospital (mean difference [MD] 0.37; 95% CI - 2.56, 3.31) and ICU (MD 0.36; 95% CI - 0.81, 1.53) stays, mechanical ventilation use (RR 0.92; 95% CI 0.68-1.24; RD 2.8% fewer), and adverse events (RR 0.98; 95% CI 0.84-1.14; RD 0.5% fewer) of patients with COVID-19. Sensitivity analysis using a fixed-effects model indicated that IVIg may reduce mortality (RR 0.76; 95% CI 0.60-0.97), and increase length of hospital stay (MD 0.68; 95% CI 0.09-1.28). CONCLUSION: Very low to moderate certainty of evidence indicated IVIg may not improve the clinical outcomes of hospitalized patients with COVID-19. Given the discrepancy between the random- and fixed-effects model results, further large-scale and well-designed RCTs are warranted.

Tandem Addition/Cyclization/Halogenation Reaction of Difluoromethylated N-Acylhydrazones with Allyltrimethylsilanes.

As novel difluoromethyl building blocks, difluoromethylated N-acylhydrazones react with allyltrimethylsilanes and the halogen source via a tandem addition/cyclization/halogenation strategy, which produces various difluoromethylpyrazoline compounds in good yields. The method features mild reaction conditions, broad substrate scopes, and a transition metal-free process with easy operation. It also proves that difluoromethylated N-acylhydrazones are useful difluoromethyl building blocks for the construction of difluoromethylated nitrogen heterocycles.

Synthesis of Difluoromethylated Pyrazoles by the [3 + 2] Cycloaddition Reaction of Difluoroacetohydrazonoyl Bromides.

As novel and efficient difluoromethyl building blocks, difluoroacetohydrazonoyl bromides have been synthesized for the first time. The synthetic utility of this reagent for the construction of difluoromethyl organic compounds is demonstrated by their effective regioselective [3 + 2] cycloaddition reactions with ynones, alkynoates, and ynamides. The reactions provide a novel and efficient protocol to access difluoromethyl-substituted pyrazoles in good to excellent yields.

Synthesis of 3-Trifluoromethyl-1,2,4-triazolines and 1,2,4-Triazoles via Tandem Addition/Cyclization of Trifluoromethyl N-Acylhydrazones with Cyanamide.

A tandem addition/cyclization reaction between trifluoromethyl N-acylhydrazones and cyanamide is described, which provides a novel and efficient process for the synthesis of polysubstituted 3-trifluoromethyl-1,2,4-triazolines and their derivatives. The method has the advantages of mild reaction conditions, a broad substrate scope, good product yields, and atom economy.

A Bibliometric Analysis of Overall and Top 100 Most-Cited Studies About Robotic Surgery Versus Open Surgery.

BACKGROUND: In the last 30 years, significant progress in the field of surgery has been achieved with the advent of robotic surgery. In this study, we aimed to conduct a bibliometric analysis to identify the distribution and characteristics overall and of the top 100 most-cited studies about robotic surgery versus open surgery. METHODS: A systematic search was conducted on March 26, 2021 using Web of Science Core Collection. Two reviewers independently screened documents, and the top 100 most-cited studies were identified. Excel 2019 and VOSviewer were used to collect the data, and visual information was obtained. RESULTS: A total of 2306 documents were searched from the Web of Science Core Collection, and 1065 journals and 2913 institutes were extracted. A significant growth was observed in the last 15 years. The number of citations from the United States accounted for 33.31% of the total number of citations. There were nine American institutes and one Swedish institute in the top 10 institutes. Four journals in the field of urology or gynecology were present in the top 10 published journals. Few global communications between authors, institutes, and countries authors were observed. CONCLUSION: The lack of close cooperation among scientific research institutions may have affected the industrialization process of surgical robots. Some developing countries, including South America and Africa, should seize the development opportunity of robotic surgery to improve the level of domestic research on robotic surgery.

Visible Light Promotes Cascade Trifluoromethylation/Cyclization, Leading to Trifluoromethylated Polycyclic Quinazolinones, Benzimidazoles and Indoles.

Efficient visible-light-induced radical cascade trifluoromethylation/cyclization of inactivated alkenes with CF3Br, which is a nonhygroscopic, noncorrosive, cheap and industrially abundant chemical, was developed in this work, producing trifluoromethyl polycyclic quinazolinones, benzimidazoles and indoles under mild reaction conditions. The method features wide functional group compatibility and a broad substrate scope, offering a facile strategy to pharmaceutically produce valuable CF3-containing polycyclic aza-heterocycles.

PCAT6 may be a new prognostic biomarker in various cancers: a meta-analysis and bioinformatics analysis.

BACKGROUND: LncRNA prostate cancer-associated transcript 6 (PCAT6) has been reported to be dysregulated in several cancers and is associated with tumor progression. Here, we have performed a meta-analysis to assess the general prognostic role of PCAT6 in malignancies. METHODS: Four public databases (Embase, Pubmed, Web of Science, Cochrane Library) were used to identify eligible studies, then data was extracted and associations between prognostic indicators and clinical characteristics were combined to estimate hazard ratio (HR) or odds ratio (OR) with a 95% confidence interval (CI). Publication bias was measured using the Begg's test, and the stability of the combined results was measured using sensitivity analysis. Subsequently, results were validated using Gene Expression Profiling Interactive Analysis (GEPIA) and the National Genomics Data Center (NGDC). RESULTS: Ten studies were considered eligible for inclusion. In total, 937 patients and eight types of cancer were included. Our results revealed that overexpression of PCAT6 was significantly associated with a shorter OS (HR = 1.82; 95% CI, [1.40, 2.38]; P < 0.0001) and progression-free survival (PFS) (HR = 1.66; 95% CI, [1.22, 2.25]; P < 0.0001) in cancer patients, and that PCAT6 overexpression was significantly associated with individual tumor clinicopathological parameters, including TNM stage (OR = 0.29; 95% CI, [0.09, 0.94]; P = 0.04), gender (OR = 1.84; 95% CI, [1.31, 2.59]; P = 0.0005), and whether the tumor was metastatic (OR = 5.02; 95% CI, [1.36, 18.57]; P = 0.02). However, PCAT6 overexpression was not correlated with patient age and tumor differentiation. PCAT6 expression was significantly up-regulated in four types of cancer, which was validated using the GEPIA cohort. Combining OS and disease-free survival (DFS) of these four types of cancer revealed a shorter OS and DFS in patients with PCAT6 overexpression. PCAT6 expression in various types of cancer was also validated in NGDC. A total of eight cancers were analyzed and PCAT6 was highly expressed in all eight cancers. Further functional predictions suggest that PCAT6 is correlated with tumor prognosis, and that PCAT6 may be useful as a new tumor-specific marker. CONCLUSIONS: LncRNA PCAT6 is highly expressed in multiple cancer types and its upregulation was significantly associated with patient prognosis and poorer clinical features, thereby suggesting that PCAT6 may be a novel prognostic factor in multiple cancer types.

Non-pharmacological interventions for older adults with depressive symptoms: a network meta-analysis of 35 randomized controlled trials.

Objective: To assess the effectiveness of non-pharmacological interventions for seniors with depressive symptoms.Methods: A comprehensive literature search was performed. We conducted network meta-analysis in two ways, intervention classes (psychosocial, psychotherapy, physical activity, combined, treatment as usual) and individual intervention (11 categories). Whenever included studies used different scales, the different instruments were converted to the units of the scale most frequently used (the Geriatric Depression Scale), such that the effect size was reported as a mean difference (MD) with 95% confidence interval (CI). The risk of bias of RCTs included in this review was assessed according to the Cochrane Handbook. Bayesian NMA was conducted using R-3.4.0 software.Results: A total of 35 RCTs with 3,797 enrolled patients were included. Compared to conventional treatment, physical activity and psychotherapy resulted in significant improvements in depressive symptoms (MD: 2.25, 95%CrI: 0.99-3.56; SUCRA = 86.07%; MD: 1.75, 95% CrI: 0.90-2.64; SUCRA = 66.44%, respectively). Similar results were obtained for music (MD: 2.6; 95% CrI: 0.84-4.35;SUCRA = 80.53%), life review (MD:1.92; 95% CrI:0.71-3.14; SUCRA = 65.62%), cognitive behavioral therapy (MD: 1.27; 95% CrI: 0.23-2.38; SUCRA = 45.4%), aerobic (MD: 1.84; 95% CrI: 0.39-3.36; SUCRA = 63%) and resistance training (MD: 1.72; 95% CrI: 0.06-3.42; SUCRA = 59.24%). Network meta-regression showed that there were no statistically significant subgroup effects.Conclusions: Physical activity and psychotherapy demonstrated statistically significant superiority over conventional treatment. Music and life review therapy proved the most promising individual interventions. However, conclusions are limited by the lack of sufficient sample size and consensus regarding intervention categories and so an adequately powered study is necessary to consolidate these findings.

[Proposal of Living Evidence-based Guideline for Combination of Traditional Chinese and Western Medicine for Treatment of COVID-19].

In order to standardize the clinical diagnosis and treatment decision-making with traditional Chinese medicine for pa-tients of coronavirus disease 2019(COVID-19) and put the latest clinical study evidence into clinical practice, the international trust-worthy traditional Chinese medicine recommendations( TCM Recs) working group started the compilation of Living Evidence-based Guideline for Combination of Traditional Chinese and Western Medicine for Treatment of COVID-19 on the basis of the standards and re-quirements of WHO handbook, GRADE and RIGHT. This proposal mainly introduces the formulation methods and processes of the living guidelines in details, such as the composition of the working group, the collection and identification of clinical issues and out-comes, the production of the living systematic review and the consensus of recommendations. The guidelines will continue to monitor the clinical study evidences of TCM in the prevention and treatment of COVID-19, and conduct regular evidence updating, retrieval and screening. When there is new study evidence, the steering committee will evaluate the possibility of the evidence to change clinical practice or previous recommendations, so as to decide whether the recommendations for the guidelines shall be implemented or upda-ted. The main criteria considered in the guideline updating are as follows:(1) There are new high-quality randomized controlled trial(RCT) evidences for TCM uninvolved in the previous edition of the guidelines;(2) as for the TCM involved in the guidelines, living sys-tematic review shows that new evidence may change the direction or strength of the existing recommendations. The specific implementation of the living evidence-based guidelines will take this proposal as the study basis and framework, in order to ensure the standardization of the formulation process and methods. This will be the first exploration of the methodology for living guidelines in the field of TCM.

Synthesis of CF3-Substituted 1,6-Dihydropyridazines by Copper-Promoted Cascade Oxidation/Cyclization of Trifluoromethylated Homoallylic N-Acylhydrazines.

A highly efficient strategy for the construction of CF3-substituted 1,6-dihydropyridazines has been developed by cascade oxidation/cyclization of trifluoromethylated N-acylhydrazines. The produced 1,6-dihydropyridazines could be easily transformed to 3-trifluoromethyl pyridazine derivatives. Some of the 1,6-dihydropyridazines exhibited aggregation-induced emission (AIE). DFT calculations were conducted to explain the mechanism.

Synthesis of Polysubstituted Trifluoromethylpyridines from Trifluoromethyl-α,ß-ynones.

A novel and efficient method for synthesis of polysubstituted trifluoromethylpyridine derivatives by the Bohlmann-Rahtz heteroannulation reaction is described, which use trifluoromethyl-α,ß-ynones as trifluoromethyl building blocks to react with ß-enamino esters or ß-enamino ketones in the presence of ZnBr2 to form the trifluoromethylpyridine derivatives in good yields. The protocol has the advantages of readily available starting materials, mild reaction conditions, and high atom economy.

Visible-light-promoted acyl radical cascade reaction for accessing acylated isoquinoline-1,3(2H,4H)-dione derivatives.

A visible-light-promoted decarboxylative acyl radical acylation/cyclization cascade reaction of N-methacryloylbenzamides for accessing acylated isoquinoline-1,3(2H,4H)-dione derivatives was described. In this report, α-keto acids were used for generating acyl radicals and inducing radical acylations. This protocol features mild reaction conditions, operational practicality and a broad substrate scope.

Diastereoselective synthesis of spiro-cyclopropanyl-cyclohexadienones via direct sulfide-catalyzed [2 + 1] annulation of para-quinone methides with bromides.

An efficient sulfide-catalyzed [2 + 1] annulation of para-quinone methides (p-QMs) with diverse bromides has been achieved. This catalytic strategy provides an efficient and straightforward protocol for accessing a variety of spiro-cyclopropanyl-cyclohexadienone compounds in good to excellent yields (64% to 96% yields) with outstanding diastereoselectivities (>20 : 1 dr), displaying good functional group tolerance as well as gram-scale capacity.

Comparison of total endoscopic thyroidectomy with conventional open thyroidectomy for treatment of papillary thyroid cancer: a systematic review and meta-analysis.

BACKGROUND: Despite the fact that thyroid surgery has evolved towards minimal incisions and endoscopic approaches, the role of total endoscopic thyroidectomy (TET) in thyroid cancer has been highly disputed. We performed a systematic review and meta-analyses of peer reviewed studies in order to evaluate the safety and effectiveness of TET compared with conventional open thyroidectomy (COT) in papillary thyroid cancer (PTC). METHOD: Medical literature databases such as PubMed, Embase, the Cochrane Library, and Web of science were systematically searched for articles that compared TET and COT in PTC treatment from database inception until March 2019. The quality of the studies included in the review was evaluated using the Downs and Black scale using Review Manager software Stata V.13.0 for the meta-analysis. RESULTS: The systematic review and meta-analysis were based on 5664 cases selected from twenty publications. Criteria used to determine surgical completeness included postoperative thyroglobulin (TG) levels, recurrence of the tumor after long-term follow-up. Adverse event and complication rate scores included transient recurrent laryngeal nerve (RLN) palsy, permanent RLN palsy, transient hypocalcaemia, permanent hypocalcaemia, operative time, number of removed lymph nodes, length of hospital stay and patient cosmetic satisfaction. TET was found to be generally equivalent to COT in terms of surgical completeness and adverse event rate, although TET resulted in lower levels of transient hypocalcemia (OR 1.66; p < 0.05), a smaller number of the retrieved lymph nodes (WMD 0.46; p < 0.05), and better cosmetic satisfaction (WMD 1.73; p < 0.05). COT was associated with a shorter operation time (WMD - 50.28; p < 0.05) and lower rates of transient RLN palsy (OR 0.41; p < 0.05). CONCLUSIONS: The results show that in terms of safety and efficacy, TET was similar to COT for the treatment of thyroid cancer. Indeed, the tumor recurrence rates and the level of surgical completeness in TET are similar to those obtained for COT. TET was associated with significantly lower levels of transient hypocalcemia and better cosmetic satisfaction, and thus is the better option for patients with cosmetic concerns. Overall, randomized clinical trials and studies with larger patient cohorts and long-term follow-up data are required to further demonstrate the value of the TET.

Effectiveness and safety assessment of drospirenone/ethinyl estradiol tablet in treatment of PCOS patients: a single center, prospective, observational study.

BACKGROUND: To investigate the effectiveness and safety of 3 mg drospirenone and 20 µg ethinyl estradiol tablet (3 mg DRSP/20 µg EE) in the treatment of polycystic ovary syndrome (PCOS). METHODS: This single center, prospective observational study was conducted in 140 patients with PCOS. They were prescribed 3 mg DRSP/20 µg EE in a 24/4/ regimen for 3 months. Patients were instructed to take oral DRSP/EE tablets (once daily) on the 2nd day of menstruation, for 28 consecutive days for 1 cycle. After 3 months of treatment, anthropometric assessments along with variations in sex hormones related index, glucolipid metabolic index, changes in bilateral ovarian volume, as well as adverse effect of the combination were evaluated. RESULTS: When compared to baseline, body mass index (BMI, 22.07 ± 4.09 vs. 21.35 ± 3.22, p < 0.001) and waist hip ratio (WHR, 0.86 ± 0.07 vs. 0.854 ± 0.06, p = 0.026) decreased significantly after treatment. Sex-hormones such as luteinizing hormone (LH) (10.88 vs. 5.81 U/L), testosterone (T) (1.85 vs. 1.51 nmol/L) and free androgen index (FAI) (5.37 vs. 1.50) decreased significantly after treatment (p < 0.001). Follicular stimulating hormone (FSH) increased significantly at 3 months as compared to before treatment (5.13 vs. 5.42 U/L, p = 0.009). Plasma insulin (11.03 vs. 11.10 pmol/L), fasting (4.97 vs. 4.93 mmol/L) and 2 h-blood glucose levels (7.18 vs. 7.04 mmol/L) did not change when compared to baseline. Plasma triglycerides (TG, 1.32 vs. 1.65 mmol/L) significantly increased 3 months after treatment when compared to before treatment (p < 0.001). However, high density lipoprotein-cholesterol (HDL-C) levels increased significantly after treatment (1.41 vs. 1.57 mmol/L, p < 0.001). It was seen that, when compared to baseline, bilateral ovarian volume (left and right) was significantly lower after treatment (p < 0.05). It was seen that 81 patients reported no adverse reactions. Of the common discomforts reported, breast swelling and pain, gastrointestinal disorder and dizziness and headache were most frequent. CONCLUSIONS: Treatment of PCOS patients with3 mg DRSP/20 µg EE has shown beneficial hormonal and lipid profile along with considerable safety profile. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900022001, March 2019, retrospectively registered.

Tin Powder-Promoted Cascade Condensation/Allylation/Lactamization: Synthesis of Isoindolinones and Pyrazoloisoindol-8-ones.

An efficient tin powder-promoted cascade condensation/allylation/lactamization of 2-formylbenzoic acids, hydrazides, and allyl bromides was developed for the synthesis of isoindolinones in good to excellent yields under mild conditions without any other additives or catalysts. Further manipulation of isoindolinones by iodocyclization process afforded the tricyclic tetrahydro-8 H-pyrazolo[5,1- a]isoindol-8-one derivatives, which could be converted into more complicated tetracyclic tetrahydro-4 H-azirino[1',2':2,3]pyrazolo[5,1- a]isoindol-4-ones.