TACE with dicycloplatin in patients with unresectable hepatocellular carcinoma: a multicenter randomized phase II trial.

OBJECTIVES: To investigate the efficacy and safety of dicycloplatin as chemotherapeutic regimen in transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). METHODS: In this randomized, open-label, phase II trial, patients with unresectable HCC who were TACE treatment-naïve or experienced recurrence after surgical resection or ablation were enrolled at 7 centers in China from March 2019 to November 2019. Participants were randomly assigned (1:1:1) to receive TACE with chemotherapeutic regimen of dicycloplatin alone (group A1), dicycloplatin plus epirubicin (group A2), or epirubicin alone (group B). The primary endpoint was objective response rate (ORR). The secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and safety. RESULTS: The ORR at 6 months in group A1 (n = 22) was significantly better than that in group B (p = 0.093; 90% confidence interval [CI], 1.03-9.45). The DCR in group A1 was significantly higher than that in group B (p = 0.045; 90% CI, 1.29-12.88). There was no significant difference in DOR among the groups (p = 0.271). The median PFS were 6.00 and 3.05 months in groups A2 (n = 25) and B (n = 24), respectively (p = 0.061). Grade 3 or worse adverse events were similar among groups in the safety population (p = 0.173). CONCLUSION: TACE with dicycloplatin was comparably safe and well tolerable as epirubicin alone in patients with unresectable HCC. Compared with epirubicin alone, significant improvement in ORR and DCR when dicycloplatin was applied, as well as prolonged PFS when dicycloplatin plus epirubicin was applied, was generated. KEY POINTS: • To our knowledge, this is the first multicenter randomized trial to assess the efficacy and safety of TACE with dicycloplatin in patients with unresectable HCC. • This phase II trial showed that TACE with dicycloplatin alone or plus epirubicin was comparably safe and well tolerable as epirubicin alone. • Significant improvements in ORR, DCR when dicycloplatin was applied, and prolonged PFS when dicycloplatin plus epirubicin was applied were recorded compared with epirubicin alone.

Catalyst-Dependent Stereospecific [3,3]-Sigmatropic Rearrangement of Sulfoxide-Ynamides: Divergent Synthesis of Chiral Medium-Sized N,S-Heterocycles.

Medium-sized N,S-heterocycles have received tremendous interest due to their biological activities and potential medical applications. However, asymmetric synthesis of these compounds are extremely rare. Described herein is a catalyst-dependent [3,3]-sigmatropic rearrangement of sulfoxide-ynamides, enabling divergent and atom-economic synthesis of a series of valuable medium-sized N,S-heterocycles in moderate to good yields with broad substrate scope. Importantly, excellent enantioselectivities have been achieved via an unprecedented chirality-transfer. Moreover, theoretical calculations are employed to elucidate the origins of the catalyst-dependent stereospecific [3,3]-rearrangement.

Efficacy and safety of low-dose everolimus combined with endocrine drugs for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer.

BACKGROUND: To analyze the efficacy and safety of everolimus 5 mg/day in combination with endocrine drugs in the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer using real-world clinical data. METHODS: Clinical data of hormone receptor (HR)-positive and HER2-negative patients with advanced breast cancer treated with everolimus combined with endocrine drugs in our center between August 2012 and May 2017 were retrospectively analyzed. Curative effect and adverse reactions were evaluated. RESULTS: A total of 110 patients were enrolled in this study, and 87.3% received salvage chemotherapy. The median number of salvage treatment lines was 5 (range: 1-19). The median follow-up duration was 12 months (range: 1-56.3 months), the overall response rate (ORR) was 6.4%, the clinical benefit rate (CBR) was 31.8%, the median progression-free survival (mPFS) was 4.0 months (95% CI: 2.9-5.1 months), and the median overall survival (OS) was 17 months (95% CI: 12.1-21.9 months). The mPFS for patients who received ≤2 treatment line was 11.8 months (95% CI: 4.3-19.3 months). Univariate and multivariate analyses suggested that absence of liver metastases, secondary endocrine resistance, and number of metastasis sites <3 were the main factors influencing the benefit of everolimus combined with endocrine therapy. The most common adverse events of grade 3 were: stomatitis (5.5%), non-infectious pneumonia (1.8%), and erythra (1.8%). No grade 4 adverse reactions were observed. CONCLUSIONS: Our results showed that everolimus (5 mg/day) combined with endocrine therapy was effective and relatively safe for patients with hormone receptor-positive, HER2-negative metastatic breast cancer.

Efficiency of Pb, Zn, Cd, and Mn Removal from Karst Water by Eichhornia crassipes.

This study experimentally investigated heavy metal removal and accumulation in the aquatic plant Eichhornia crassipes. Pb, Zn, Cd, and Mn concentrations, plant morphology, and plant functional groups were analyzed. Eichhornia crassipes achieved high removal efficiency of Pb and Mn from karst water (over 79.5%), with high proportion of Pb, Zn, and Cd absorption occurring in the first eight days. The highest removal efficiencies were obtained at initial Pb, Zn, Cd, and Mn concentrations of 1 mg/L, 2 mg/L, 0.02 mg/L, and 0.2 mg/L, respectively. Eichhornia crassipes exhibited a high bioconcentration factor (Mn = 199,567 > Pb = 19,605 > Cd = 3403 > Zn = 1913) and a low translocation factor (<1). The roots accumulated more Pb, Zn, Cd, and Mn than the stolons and leaves due to the stronger tolerance of roots. The voids, stomas, air chambers, and airways promoted this accumulation. Pb, Cd, Zn, and Mn likely exchanged with Mg, Na, and K through the cation exchange. C≡C, C=O, SO42-, O-H, C-H, and C-O played different roles during uptake, which led to different removal and accumulation effects.

Copper-catalyzed tandem cis-carbometallation/cyclization of imine-ynamides with arylboronic acids.

An efficient copper-catalyzed tandem regioselective cis-carbometallation/cyclization of imine-ynamides with arylboronic acids has been developed. This method leads to a facile and practical synthesis of valuable 2,3-disubstituted indolines in moderate to excellent yields and features a broad substrate scope and wide functional group tolerance. Other significant features of this protocol include the use of readily available starting materials, high flexibility, simple procedure and mild reaction conditions.

Effects and Mechanisms of Calcium Ion Addition on Lead Removal from Water by Eichhornia crassipes.

Karst water is rich in calcium ions (Ca2+) and exhibits poor metal availability and low biodegradation efficiency. This study sought to analyze the effects and mechanisms of Ca2+ on lead (Pb) removal and absorption by Eichhornia crassipes (a floating plant common in karst areas). Moreover, the morphology and functional groups of E. crassipes in water were characterized via SEM, and FTIR. The results demonstrated that the removal rate of Pb in karst water (85.31%) was higher than that in non-karst water (77.04%); however, the Pb bioconcentration amount (BCA) in E. crassipes roots in karst water (1763 mg/kg) was lower than that in non-karst water (2143 mg/kg). With increased Ca2+ concentrations (60, 80, and 100 mg/L) in karst water, the Pb removal rate increased (85.31%, 88.87%, and 92.44%), the Pb BCA decreased (1763, 1317, and 1095 mg/kg), and the Ca BCA increased (6801, 6955, and 9368 mg/kg), which was attributed to PbCO3 and PbSO4 precipitation and competitive Ca and Pb absorption. High Ca2+ concentrations increased the strength of cation exchange, alleviated the fracture degree of fibrous roots, reduced the atrophy of vascular bundles, protected the cell wall, promoted C-O combined with Pb, enhanced the strength of O‒H, SO42-, C=O, and reduced the oxidization of alkynyl acetylene bonds.

[Water Quality Analysis and Health Risk Assessment for Groundwater at Xiangshui, Chongzuo].

To investigate the environmental quality and human health risks of different types of groundwater at Xiangshui, Chongzuo, several regular water quality indexes and concentrations of metals in 60 groundwater samples were measured and analyzed. The environmental quality of groundwater was analyzed by means of the Nemerow index. The health risks were assessed by using a human health risk assessment model. The regular water quality indexes and concentrations of metals of the well water, spring water, and underground river water exceeded the standards to different degrees. The environmental quality of groundwater was at a poor grade. The comprehensive evaluation score of underground river water (F=4.26) was the lowest. The well water had the same score as spring water (F=7.10). The high hardness and salinity were conducive to enrichment of Cr, and the reducing environment was of great advantage for the enrichment of As. The environmental geochemistry of Zn, Pb, Cd, and Cu was similar. The sources of Fe, Al, and Mn were similar. The results of the health risk assessment indicated that the health risks of well water, spring water, and underground river water were relatively high. The health risks decreased in the order of well water > underground river water > spring water. The health risks mainly came from the carcinogenic metallic element Cr. Carcinogenic risks were 4-6 orders of magnitude higher than non-carcinogenic risks. Carcinogenic risks were higher than the maximum allowance levels (5.0×10-5 a-1). Non-carcinogenic risks were lower than the allowance levels (10-6 a-1). Children had greater health risks than adults. The health risks of metals through the drinking pathway were 2-3 orders of magnitude higher than the values caused by the dermal contact pathway. For the sake of drinking water safety, the well water, underground river water, and spring water should be properly treated and the concentration of Cr in groundwater should be controlled before drinking.

Stereoselective synthesis of 2,5-disubstituted pyrrolidines via gold-catalysed anti-Markovnikov hydroamination-initiated tandem reactions.

A series of gold-catalysed intramolecular anti-Markovnikov hydroamination-initiated azidation, allylation and heteroarylation reactions of chiral homopropargyl sulfonamides have been developed. Various enantioenriched 2,5-disubstituted pyrrolidines are obtained in moderate to excellent yields with excellent enantioselectivities and generally high diastereoselectivities.

[Major Ionic Characteristics and Controlling Factors of Karst Groundwater at Xiangshui, Chongzuo].

To investigate the major ionic characteristics, seasonal variation, and controlling factors of karst groundwater at Xiangshui, Chongzuo, 210 groundwater samples were collected and measured in wet season, dry season, and flat season in 2016. The controlling factors of karst groundwater were analyzed by using multivariate statistical analysis method. The results showed that the groundwater samples were weakly alkaline fresh water and rich in Ca2+ and HCO3-, which accounted for more than 75% and 70% of total ion concentration. The average concentrations of K+, Na+, Cl-, and NO3- decreased in the order of wet season > flat season > dry season. None of the concentrations of Ca2+, Mg2+, HCO3-, SO42-, pH, TDS, TZ+, and TZ- showed significant seasonal variation. The hydrochemical characteristics were found to be of HCO3-Ca type and mainly determined by carbonate rock dissolution. Only a small proportion of them were of HCO3·Cl-Ca and HCO3·SO4-Ca type in wet season and flat season, Cl·NO3-Ca type appeared in flat season, and HCO3-Ca·Mg type appeared in dry season, reflecting the influence of dolomite and ferric mudstone dissolution in the stratum, and of NO3- and Cl- input from anthropogenic activities. Groundwater Ca2+ and HCO3- mainly came from limestone dissolution; Na+, Cl-, K+, and NO3- came from atmospheric precipitation and human activities; while Mg2+ and SO42- came from dolomite and ferric mudstone dissolution. The chemical composition of groundwater was controlled by water-rock interaction, the groundwater in the carbonate aquifer was controlled by carbonate rocks dissolution, and the groundwater in villages and densely populated areas was affected by atmospheric precipitation and human activity.

Zinc-catalyzed reaction of isoxazoles with thioynol ethers involving an unprecedented 1,2-sulfur migration.

A novel zinc-catalyzed reaction of isoxazoles with thioynol ethers involving an unprecedented 1,2-sulfur migration has been developed, which represents the first example of a non-noble metal-catalyzed reaction between isoxazoles and alkynes. This method allows the facile and atom-economical synthesis of a range of valuable ß-keto enamides. Moreover, the computational study provides further evidence for the feasibility of the proposed reaction mechanism.

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.

Efficient and practical synthesis of enantioenriched 2,3-dihydropyrroles through gold-catalyzed anti-Markovnikov hydroamination of chiral homopropargyl sulfonamides.

A direct gold-catalyzed 5-endo-dig cycloisomerization of chiral homopropargyl sulfonamides has been developed. A range of enantioenriched 2,3-dihydropyrroles are readily accessed by utilizing this approach. Importantly, this gold-catalyzed cycloisomerization reaction proceeds through an anti-Markovnikov addition by using a catalytic base as the additive, which completely suppresses the undesired dimerization.

Gold-catalyzed intermolecular oxidation of o-alkynylbiaryls: an easy and practical access to functionalized fluorenes.

A novel gold-catalyzed intermolecular oxidation of o-alkynylbiaryls has been developed. A variety of functionalized fluorenes are readily accessed by utilizing this non-diazo approach, thus providing a viable alternative to synthetically useful fluorenes.

Flexible and practical synthesis of 3-oxyindoles through gold-catalyzed intermolecular oxidation of o-ethynylanilines.

A novel gold-catalyzed intermolecular oxidation of o-ethynylanilines has been developed. A range of functionalized 3-oxyindoles are readily accessed by utilizing this strategy. Importantly, this gold-catalyzed oxidative process outcompetes the typical indole formation.

[Clinical features of multiple canal involvement in benign paroxysmal positional vertigo].

OBJECTIVE: To describe a series of patients with multiple canal involvement in benign paroxysmal positional vertigo (BPPV), with respect to diagnosis and management. METHODS: Ninety-five individuals with symptoms of BPPV and positional nystagmus were included in this study. The diagnosis was based on a history of brief episodes of vertigo and the presence of multiple positional nystagmus as confirmed by video-oculographic examination. Patients were treated by means of different particle repositioning manoeuvres according to the affected canal. RESULTS: Ninety-five patients showed multiple positional nystagmus during the examination corresponding to simultaneous multi-canal BPPV. Fourteen patients (14.7%) had bilateral canal BPPV. Six patients had bilateral posterior canal. Six patients had bilateral horizontal canal, and two patients had bilateral anterior canal. Fifty-three patients (55.8%) had torsional, up-beating nystagmus with down-beating nystagmus, which suggested possible affected both of posterior and anterior canals. Twenty patients (21.1%) had torsional up-beating nystagmus and horizontal direction nystagmus, which suggested possible affected both of posterior and horizontal canals. Five patients had down-beating nystagmus with horizontal nystagmus, which suggested affected both of anterior and horizontal canals. Three patients had torsional up-beating with down-beating and horizontal nystagmus, which suggested possible affected multiple canals. Treatment given to the patients varied according to the canal affected, started with the canal that elicited a strong positional nystagmus and vertigo, and 93.7% (89/95) of patients were symptom free or improved. CONCLUSIONS: It has been found that multi-canal BPPV is not a rate observation in clinic, and most of them affected posterior and anterior canals. Treatment of multi-canal BPPV can be effective using repositioning maneuver.

[Vestibular pathology associated with noise-induced inner ear impairment].

OBJECTIVE: To evaluate the pathological status of the vestibular system associated with noise-induced inner ear impairment. METHODS: Totally 68 patients with noise-induced hearing loss (NIHL) who presented with vestibular symptoms including vertigo, dizziness, and chronic disequilibrium were screened. All patients underwent a series of conventional vestibular function tests and vestibular autorotation test and the results were retrospectively reviewed and evaluated. RESULTS: Sixty-eight (14.5%) patients with NIHL were identified among 469 patients with vertigo, dizziness, or imbalance. A pure tone hearing threshold of patients with vertigo and NIHL at 4000 Hz were between 30 dB HL and 80 dB HL with an average threshold of (46.7 +/- 17.6) dB HL in left ear and (37.3 +/- 16.7) dB HL in right ear. Patients with symmetrical hearing loss at 4000 Hz accounted for 41.7% and those with asymmetrical loss accounted for 58.3%. Vestibular pathologies included benign positional paroxysmal vertigo (45.7%), unilateral decreased caloric responses (20.0%), bilateral decreased caloric responses (26.7%), abnormal vestibulo-spinal reflex function (28.6%), vestibular function response hyperactivity (3.0%), and abnormal vestibulo-ocular reflex presentation at high frequencies (97.0%). CONCLUSIONS: Loud acoustic stimulation not only damages the cochlea but also causes clear functional impairment to the vestibular end organs. Although the vestibular pathology is not correlated with the severity of the hearing loss, it correlates with the subjective symptoms of the vestibular system.

[Diagnosis and therapy for benign paroxysmal positional vertigo of the anterior semicircular canal].

OBJECTIVE: To analyse the video-oculographic findings of positional tests and evaluate the efficacy of canalith repositioning procedure (CRP) in patients with paroxysmal positional vertigo ( BPPV) of the anterior semicircular canal (ASC). METHODS: A retrospective study of 31 patients with ASC BPPV. Then the CRP was performed. RESULTS: Twenty-two individuals (70.97%) presented a unilateral positional nystagmus during the Dix-Hallpike test, in 17 individuals had torsional nystagmus component, 5 individuals only had pure positional down beat nystagmus. Nine patients presented bilateral positional nystagmus, 7 individuals had torsional component positional nystagmus, in 2 patients the direction of the torsional component were the same during right and left Dix-Hallpike test, in 4 patients the torsional component were concurrent with positional down beat nystagmus but the direction could not be ascertained clinically, in 2 patients had pure positional down beat nystagmus. Nineteen patients (61.29%) had unilateral lesion, 11 patients had the left ASC BPPV, 8 patients had right ASC BPPV. Eleven patients had with both ASC and PSC BPPV in the ipsilateral. Twenty-one patients (67.74%) were cured, 29 patients (93.55%) were improved, 2 (6.45%) patients were inefficacy. CRP effectively resolved the nystagmus and vertigo in 14 patients (45.16%) when applied only once, The average number of CRP was 1.7 times, there were 5 patients recurrence during the follow-up. CONCLUSIONS: ASC BPPV was not a common condition. The torsional nystagmus component of ASC BPPV might be weak during the Dix-Hallpike test. The positional nystagmus of ASC BPPV was triggered bilaterally. Based on these findings, CRP could be one of the most effective treatment methods for ASC BPPV.

[Functional localization of vestibular cerebral representations in human using functional magnetic resonance imaging].

OBJECTIVE: To study human vestibular cerebral representations by combining right-sided ice-water stimulation at 0 degree C with blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) and to evaluate the value of this method in the functional localization of human vestibular cortex. METHODS: Twenty right-handed volunteers (12 men and 8 women) received unilateral irrigation of the right external auditory meatu for 15 s with 15 ml of water at 0 degrees C during fMRI in complete darkness. The functional imaging of brain cortex was acquired with a 1.5-T MRI scanner (Signa Infinity Twin + Excite; General Electric Co., USA). The successive functional images from each subject were analyzed as a group with statistical parametric mapping software (SPM 99). RESULTS: Ultimately, data obtained from 17 subjects were analyzed (3 subjects were eliminated from data because of head movement exceeding 2 mm). The group analysis showed bilateral (particularly left-sided) cortical activation, associated with caloric stimulus involving in temporoparietal junction extending into the posterior insula, supramarginal gyrus in the inferior parietal lobe, precuneus, supplementary motor area (SMA), the ventrolateral portion of the occipital lobe, cuneus and lingual gyrus, superior temporal gyrus and cingular cortex. CONCLUSIONS: Ice-water stimulation at 0 degree C in fMRI reveals a widespread cortical network involved in vestibular signal processing in human. As the functional localization of vestibular cortex could be determined precisely, ice-water stimulation at 0 degree C in fMRI would hold great promise as a sensitive and reproducible tool for the research in human vestibular cortex.

[Study on the causes and risk factors on vertigo and balance disorders in 118 elderly patients].

OBJECTIVE: To understand the various factors causing vertigo and balance disorders in the elderly. METHODS: 118 elderly patients (aged equal or older than 60 years of age) with vertigo or balance disorders were retrospectively analyzed through clinical symptoms, audio-vestibular function tests, X-ray, CT scan or MRI in cervical vertebras, brain and inner ears, ultrasonography, transcranial doppler (TCD) or magnetic resonance angiography (MRA) in blood vessels on head and neck. RESULTS: Of 118 patients, 70 (23%) of them suffered perip heral vestibular disorders while 29 (58%) having cerebral vertigo or dizzness, leaving 19 cases (16%) as unclassified. CONCLUSION: For elderly patients, vertigo and balance disorders were commonly caused by many kinds of peripheral and cerebral vestibular pathological disfunctions while the functional weakness of vestibular organs and systems affected by the physiological process of ageing and different concommitant diseases as well as environmental, psychogenic factors should also be considered.