Feasibility and tolerability of anlotinib plus PD-1 blockades as rechallenge immunotherapy in previously treated advanced ESCC: a retrospective study.

BACKGROUND: Rechallenge with immune checkpoint inhibitor (ICI) seemed favorable in several tumors, but clinical experience on esophageal squamous cell carcinoma (ESCC) was scanty. This real-world study aimed to assess the feasibility and safety of anlotinib plus ICI for patients with previously ICI-treated advanced ESCC. MATERIALS AND METHODS: We retrospectively identified advanced ESCC patients who received anlotinib plus ICI in the rechallenge setting for evaluation of clinical outcomes and safety. Totally 110 ICI-pretreated patients, of which 89 (80.9%) received prior first- or second-line treatment, were included from September 9, 2019, to November 30, 2022. Most patients (63.6%) discontinued initial ICI due to disease progression. RESULTS: After rechallenge, median overall survival (OS) and progression-free survival (PFS) were 11.1 (95% CI, 8.6-13.7) and 5.6 (95% CI, 4.4-6.8) months, respectively; estimated OS and PFS rates at 12 months were 47.6% (95% CI, 36.8%-57.7%) and 21.4% (95% CI, 10.9%-34.2%), respectively. No complete response was reported and 21 (19.1%) patients attained partial response; the objective response rate was 19.1%. Fifty-five (50.0%) had stable disease for a disease control rate of 69.1%. Of the 21 responders, median duration of response was 6.4 months. Tendencies for longer OS were observed in patients with Eastern Cooperative Oncology Group Performance of 0 (P = .056). The incidence of grade 3 or higher treatment-related adverse events was 10.0%. CONCLUSION: Anlotinib plus ICI in the rechallenge setting was promising and resulted in encouraging benefits for patients with previously ICI-treated advanced ESCC. Our findings provided preliminary but unique evidence to help select ESCC patients benefiting from this strategy. TRIAL REGISTRATION: chictr.org.cn; number ChiCTR2300070777.

[Distribution Characteristics and Risk Assessment of PPCPs in Surface Water and Sediments of Lakes in the Lower Reaches of the Huaihe River].

In order to understand the occurrence characteristics and ecological risks of pharmaceuticals and personal care products (PPCPs) in surface water and sediments of Hongze Lake and Gaoyou Lake in the lower reaches of the Huaihe River, 43 surface water and sediment samples from 23 sampling sites were collected, and 61 PPCPs were detected in the samples. The concentration level and spatial distribution of target PPCPs in Hongze Lake and Gaoyou Lake were analyzed, the distribution coefficient of typical PPCPs in the water/sediment system in the study area was calculated, and the ecological risk of target PPCPs was evaluated using the entropy method. The results showed that the PPCPs in surface water of Hongze Lake and Gaoyou Lake were 1.56-2534.44 ng·L-1 and 3.32-1027.47 ng·L-1, respectively, and those in sediment were 1.7-926.7 ng·g-1 and 1.02-289.37 ng·g-1, respectively. The concentrations of lincomycin (LIN) in surface water and doxycycline (DOX) in sediment were the highest, and antibiotics were the main components. The spatial distribution of PPCPs was higher in Hongze Lake and lower in Gaoyou Lake. The distribution characteristics of typical PPCPs in the study area showed that typical PPCPs tended to stay in the water phase, and there was a significant correlation between lg Koc and lg Kd, indicating that total organic carbon (TOC) played an important role in the distribution of typical PPCPs in the water/sediment system. The ecological risk assessment results showed that the ecological risk of PPCPs to algae in surface water and sediment was significantly higher than that of fleas and fish, the ecological risk value of PPCPs in surface water was higher than that in sediment, and the ecological risk of Hongze Lake was higher than that of Gaoyou Lake.

A small-scale neutral alumina column chromatography method for carbon isotope determination of hopanes in crude oils or rock extracts.

This paper presents a small-scale column chromatography method for separating hopanes in crude oil or rock extracts using neutral alumina as a solid phase adsorbent and a Pasteur pipette as a separation device. Three oil samples were selected to study the effect of solid phase adsorbent type and column length on the separation of hopanes. The oil samples were eluted with mixed reagents (V hexane: V petroleum ether = 8:2) and collected at intervals of 0.5 ml. Ten Fractions were collected and tested for the compounds using GC-MS. A quantitative approach was used to reveal distribution characteristics of compounds in each eluted Fraction. Experimental results showed that 100-200 um neutral alumina exhibited significant differences in the adsorptive capacity of biomarkers from oil samples and rock extracts. The elution order of the biomarkers in the chromatographic column (the length is 180 mm) was n-alkanes, steranes and hopanes. The separation of hopanes could be realized by collecting the eluted Fractions 4 and 5. Compared with the urea complexation, the purity of hopanes separated by column chromatography was higher. The concentration of n-alkanes (nC16-nC34) could be reduced from 1.99 to 4.83 mg/ml to 0.79-0.94 mg/ml, and the content of steranes can be reduced from the original 12% to 0.45%. Residual n-alkanes and steranes were not visible in the GC-MS detection. The Total Ion Chromatography (TIC) of hopanes was consistent with the distribution characteristics of the m/z191 mass chromatogram. The isolated hopanes could meet the detection requirements of isotope ratio mass spectrometry. The C29Ts/C29αß ratio of hopanes decreased gradually from 1.63 to 0.73 as the column length increased. It is speculated that the variation of the C29Ts/C29αß ratio is not only affected by maturity but also by the oil and gas migration. This method is a new attempt in the field of compound purification and can be widely used in the study of stable carbon isotopes of hopanes monomeric hydrocarbons.

ERp44 Regulates the Proliferation, Migration, Invasion, and Apoptosis of Gastric Cancer Cells Via Activation of ER Stress.

Gastric cancer (GC) is one of the most prevalent malignancies worldwide. Endoplasmic reticulum (ER) stress plays a key role in the progression of GC. Rapid proliferation of tumor cells interferes with ER homeostasis, leading to ER stress and triggering unfolded protein response. Therefore, it is very necessary to investigate abnormally expressed ER resident proteins (ERp) in cancer cells. This study aimed to investigate the possible roles of ERp44. The mRNA and protein expression of genes were detected using qRT-PCR and western blot. Cell apoptosis was calculated using flow cytometry. Cell proliferation was determined using CCK-8 and colony formation assay. Cell migration was detected by wound healing, and cell invasion was measured by transwell assay. We found that ERp44 was obviously decreased in GC tissues. Furthermore, ERp44 overexpression distinctly suppressed the proliferation, migration, and invasion of MGC-803 and KATO III cells. In contrast, apoptosis was promoted by ERp44 overexpression. Furthermore, mechanistic studies revealed that overexpression of ERp44 inhibited malignant biological processes by regulating the eIF-2α/CHOP signaling pathway. Taken together, our data demonstrated that ERp44 regulated the proliferation, migration, invasion, and apoptosis via ERp44/eIF-2α/CHOP axis in GC. Targeting the ERp44and ER stress may be a promising strategy for GC.

The complete chloroplast genome of Phoebe minutiflora (Lauraceae).

Phoebe minutiflora H. W. Li, is a member of the Lauraceae family, while its generic relationship has been long-term controversial. The complete chloroplast (cp) genome of P. minutiflora was first reported in this paper. The cp genome was 152,654 bp in length with four typical quadripartite structures, which was consisted of a large single-copy (LSC) region of 93,697 bp, a small single-copy (SSC) region of 18,809 bp, and two inverted repeats (IRs) of 20,074 bp. In addition, there were a total of 112 unique genes, including 79 protein-coding genes, 29 tRNA genes, and four rRNA genes. The phylogenetic analysis indicated that P. minutiflora should be placed into Machilus.

Research Progress in Plant Molecular Systematics of Lauraceae.

Lauraceae is a large family of woody plants with high ecological and economic value. The tribal and generic division and phylogenetic relationship of Lauraceae have long been controversial. Based on morphological and molecular evidence, phylogenetic relationships within the Cinnamomeae, Laureae and Perseeae tribes, also called 'the Core Lauraceae', have arisen particular attention. In this review, we comprehensively collated the literatures on the phylogeny of Lauraceae published in recent years and summarized progress made in molecular systematic researches employing gene fragments, chloroplast genomes and DNA barcodings analyses. We clarified the phylogenetic relationships and main controversies of 'the Core Lauraceae', the systemic position of fuzzy genera (Neocinnamomum, Caryodaphnopsis and Cassytha) and the development of chloroplast genome and DNA barcodes. We further suggested and proposed the whole genome analysis and different inflorescence types would be possible to provide more information for further research on phylogenetic relationships and taxonomy of Lauraceae.

Development and characterization of 20 novel EST-SSR markers for Pteroceltis tatarinowii, a relict tree in China.

PREMISE: Pteroceltis tatarinowii (Ulmaceae), the only species of the genus Pteroceltis, is an endangered tree in China. Here, novel expressed sequence tag-simple sequence repeat (EST-SSR) markers were developed to illuminate its genetic diversity for conservation and assisted breeding. METHODS AND RESULTS: Based on Illumina transcriptome data from P. tatarinowii, a total of 70 EST-SSR markers were initially designed and tested. Forty-eight of 70 loci (68.6%) were successfully amplified, of which 20 were polymorphic. The number of alleles per locus ranged from two to six, and the levels of observed and expected heterozygosity ranged from 0.018 to 0.781 and from 0.023 to 0.702, respectively. Additionally, cross-amplification was successful for 17 loci in two related species, Ulmus gaussenii and U. chenmoui. CONCLUSIONS: These new EST-SSR markers are valuable transcriptomic resources for P. tatarinowii and will facilitate population genetics and molecular breeding of this species and its relatives in Ulmaceae.

POM121 overexpression is related to a poor prognosis in colorectal cancer.

Background: Nuclear pore membrane protein 121 (POM121) plays a crucial role in nucleocytoplasmic transport, but its significance in tumorigenesis and the progression of colorectal cancer (CRC) remains unknown. The aim of this study was to evaluate the relationship between POM121 and CRC.Methods: POM121 expression in colorectal tissues was analyzed at both the gene and protein levels. We investigated the connection between POM121 expression and clinicopathological features, as well as overall survival. A gene set enrichment analysis (GSEA) was performed, and a protein-protein interaction (PPI) network was constructed to determine the mechanism of POM121 in CRC.Results: CRC tissues displayed a striking increase in POM121 expression compared with colonitis and pericarcinomatous mucosa tissues (66.61% vs 24.36% vs 24.11%, respectively, p < 0.0167). POM121 overexpression was significantly associated with lymph node metastasis, distant metastasis, TNM stage, venous invasion, perineural invasion, preoperative CEA and CA19-9 levels, and Ki67 expression. CRC patients with high POM121 levels tended to have poor overall survival rates. POM121 may participate in the regulation of the cell cycle and DNA repair in CRC.Conclusions: Our results suggest that POM121 has the potential to serve as a novel prognostic biomarker in CRC patients.

Characterization of the first complete chloroplast genome sequence of Celtis sinensis (Cannabaceae) and its phylogenetic implications.

Celtis sinensis Pers. is a popular garden landscape tree in riparian areas and a valuable resistant tree in many extreme environments. Here, we determined the first complete chloroplast genome of C. sinensis using high-throughput sequencing technology. Our results showed the chloroplast genome of C.sinensis was 159,092 bp long and displayed a typical quadripartite structure consisting of a pair of inverted repeats with a length of 26,895 bp and separating by two single-copy regions (LSC, 86,085 bp and SSC, 19,217 bp). Besides, the chloroplast genome of C. sinensis totally contained 131 genes, including 87 protein coding genes, 36 transfer RNAs and eight ribosomal RNAs. Additionally, a maximum likelihood phylogenetic analysis based on the 19 chloroplast genomes demonstrated the monophyly of Cannabaceae and C. sinensis formed a sister clade to Celtis biondii.

[Particle Size Distribution and Pollutant Speciation Analyses of Stormwater Runoff in the Ancient Town of Suzhou].

The particle size distribution (PSD) and its transformation processes in the stormwater runoffs in the ancient town of Suzhou were studied based on the particles size analyses, the water-quality monitoring data and the parameters of the rainfall-runoff models. The commercial districts, the modern residential area, the old residential area, the traffic area and the landscape tourist area were selected as the five functional example areas in the ancient town of Suzhou. The effects of antecedent dry period, the rainfall intensity and the amount of runoffs on the particle size distributions were studied, and the existing forms of the main pollutants in different functional areas and their possible relations were analyzed as well. The results showed that the particle size distribution, the migration processes and the output characteristics in the stormwater runoffs were greatly different in these five functional areas, which indicated different control measures for the pollution of the runoffs should be taken in the design process. The antecedent dry period, the rainfall intensity and the amount of runoffs showed significant correlations with the particle size distribution, showing these were the important factors. The output of the particles was greatly influenced by the flow scouring in the early period of the rainfall, and the correlations between the amount of runoffs and the particle migration ability presented significant difference in 30% (early period) and 70% (later period) of the runoff volume. The major existence form of the output pollutants was particle, and the correlation analyses of different diameter particles showed that the particles smaller than 150 microm were the dominant carrier of the pollutants via adsorption and accumulation processes.

Potential roles of abnormally expressed long noncoding RNA UCA1 and Malat-1 in metastasis of melanoma.

Melanoma is a highly aggressive skin cancer with increasing incidence worldwide. Long noncoding RNAs (lncRNAs), a group of nonprotein-coding transcripts longer than 200 nucleotides, are pervasively transcribed in the genome and are emerging as new players in tumorigenesis. The primary objective of this study was to investigate the role of six cancer-related lncRNAs in pairs of melanoma and adjacent normal tissues (ANTs). A total of 63 primary melanoma, paired ANTs, and metastatic lesions were collected in a Chinese population. Real-time PCR analysis was carried out to compare a series of cancer-related lncRNAs among primary melanoma tissues, ANTs, and metastatic lesions. In in-vitro studies, transwell migration assay was carried out to estimate the migration abilities of melanoma cells with different expression levels of urothelial carcinoma-associated 1 (UCA1) or metastasis-associated lung adenocarcinoma transcript 1 (Malat-1) lncRNAs. We found that UCA1 and Malat-1 lncRNAs were markedly more increased in melanomas than in paired ANTs (P<0.05). Melanomas at later stages (stages 3-4) showed higher expression of UCA1 lncRNA than those at early stages (stages 1-2) (P=0.455). In melanomas with lymph node metastasis, the metastatic lesions had a relatively higher expression of Malat-1 lncRNA than in paired primary tumors (P=0.414). Knockdown of UCA1 or Malat-1 lncRNA could attenuate the migrational ability of melanoma cells in in-vitro studies. Increased expression of UCA1 and Malat-1 lncRNAs might have a correlation with melanoma metastasis.

[Impacts of bleeding and cupping therapy on serum P substance in patients of postherpetic neuralgia].

OBJECTIVE: To observe the effect of bleeding and cupping therapy on postherpetic neuralgia (PHN) and preliminarily discuss the analgesic mechanism. METHODS: Sixty-four cases of PHN were randomized into two groups, 32 cases in each one. In the bleeding and cupping group, the local pricking with syringe needle and cupping was applied in the local painful area, once every two days. And totally 8 treatments were required. In the pregabalin group, pregabalin was prescribed for oral administration, 150mg/time, twice a day. And totally 16 days of medication were required. Visual analogue scale (VAS) score and the changes of P substance content in the peripheral and local serum before and after treatment were observed in the two groups. METHODS: VAS score and peripheral serum P substance after treatment were lower significantly than those before treatment in the two groups (all P<0.01). The result in the bleeding and cupping group was much more significant (P<0.01). The local serum P substance after treatment was reduced significantly than that before treatment in the bleeding and cupping group [(93.86 +/- 9.87) pg/mL vs (46.13 +/- 6.31) pg/mL, P<0.01]. CONCLUSION: Bleeding and cupping therapy achieves the definite efficacy on PHN and it can reduce significantly peripheral and local serum P substance content in the patients. It is possibly one of the mechanisms of analgesic effect.

Clinical efficacy of flumetasone/salicylic acid ointment combined with 308-nm excimer laser for treatment of psoriasis vulgaris.

OBJECTIVE: To compare the clinical efficacy and safety of combining flumetasone ointment with 308-nm excimer laser therapy vs. 308-nm excimer laser monotherapy for the treatment of psoriasis vulgaris. METHOD: Forty patients with psoriasis vulgaris were recruited; 20 were treated with flumetasone ointment plus 308-nm excimer laser therapy, and the other 20 received only excimer laser monotherapy. The flumetasone ointment was applied topically twice a day, and laser treatments were scheduled twice weekly for a total of 10 treatments. Clinical efficacy was evaluated in a blinded manner by two independent physicians using photographs taken before and after treatment. RESULTS: Of the 40 patients who received and completed the entire course of therapy, the psoriasis area and severity index score was improved by 82.51 ± 11.24% and 72.01 ± 20.94% in the combination group and laser group, respectively (P > 0.05), and the average cumulative dose was 5.06 ± 2.20 j/cm(2) in the combination group and 7.75 ± 2.25 j/cm(2) in the laser-only group, respectively (P < 0.05). CONCLUSION: The clinical data suggest that combination treatment using flumetasone ointment and a 308-nm excimer laser is superior to laser monotherapy for treatment of psoriasis vulgaris. The combination therapy can increase effectiveness and decrease the total laser dose, thus potentially reducing side effects.