Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival.

Muscle wasting and cachexia have long been postulated to be key determinants of cancer-related death, but there has been no direct experimental evidence to substantiate this hypothesis. Here, we show that in several cancer cachexia models, pharmacological blockade of ActRIIB pathway not only prevents further muscle wasting but also completely reverses prior loss of skeletal muscle and cancer-induced cardiac atrophy. This treatment dramatically prolongs survival, even of animals in which tumor growth is not inhibited and fat loss and production of proinflammatory cytokines are not reduced. ActRIIB pathway blockade abolished the activation of the ubiquitin-proteasome system and the induction of atrophy-specific ubiquitin ligases in muscles and also markedly stimulated muscle stem cell growth. These findings establish a crucial link between activation of the ActRIIB pathway and the development of cancer cachexia. Thus ActRIIB antagonism is a promising new approach for treating cancer cachexia, whose inhibition per se prolongs survival.

Portal vein velocity predicts portal vein system thrombosis after splenectomy with esophagogastric devascularization.

BACKGROUND: Portal vein system thrombosis (PVST) is a potentially fatal complication after splenectomy with esophagogastric devascularization (SED) in cirrhotic patients with portal hypertension. However, the impact of portal vein velocity (PVV) on PVST after SED remains unclear. Therefore, this study aims to explore this issue. METHODS: Consecutive cirrhotic patients with portal hypertension who underwent SED at Tongji Hospital between January 2010 and June 2022 were enrolled. The patients were divided into two groups based on the presence or absence of PVST, which was assessed using ultrasound or computed tomography after the operation. PVV was measured by duplex Doppler ultrasound within one week before surgery. The independent risk factors for PVST were analyzed using univariate and multivariate logistic regression analysis. A nomogram based on these variables was developed and internally validated using 1000 bootstrap resamples. RESULTS: A total of 562 cirrhotic patients with portal hypertension who underwent SED were included, and PVST occurred in 185 patients (32.9%). Multivariate logistic regression analysis showed that PVV was the strongest independent risk factor for PVST. The incidence of PVST was significantly higher in patients with PVV ≤ 16.5 cm/s than in those with PVV > 16.5 cm/s (76.2% vs. 8.5%, p < 0.0001). The PVV-based nomogram was internally validated and showed good performance (optimism-corrected c-statistic = 0.907). Decision curve and clinical impact curve analyses indicated that the nomogram provided a high clinical benefit. CONCLUSION: A nomogram based on PVV provided an excellent preoperative prediction of PVST after splenectomy with esophagogastric devascularization.

Anatomical sectionectomy based on Takasaki's segmentation for solitary intrahepatic cholangiocarcinoma: a propensity-matched analysis.

BACKGROUND: Anatomical sectionectomy based on Takasaki's segmentation has shown advantages in hepatocellular carcinoma. However, whether this approach improves the survival of intrahepatic cholangiocarcinoma (ICC) remains unknown. METHODS: A series of 248 consecutive patients with solitary ICCs who underwent hepatectomy were studied retrospectively. The patients were classified into the groups of anatomical sectionectomy based on Takasaki's segmentation (TS group) and non-Takasaki's hepatectomy (NTH group). The bias between the two groups was minimized using propensity score matching (PSM). Recurrence-free survival (RFS) and overall survival (OS) were evaluated with Kaplan-Meier analysis. The Cox proportional hazards model was performed to determine the adverse risk factors associated with survival. RESULTS: After PSM, 67 pairs of patients were compared. Both the RFS and OS rates in the TS group were significantly better than those in the NTH group (23.2 % vs. 16.5 %, and 40.4 % vs. 27.3 %, P = 0.035 and 0.032, respectively). Multivariate analysis showed that NTH was independently associated with worse RFS and OS than TS. The stratified analysis demonstrated that the RFS and OS rates in the TS group with tumor stage I and tumor size ≥3 cm were significantly better than those in the NTH group, while the survival rates for ICC with stage I and tumor size <3 cm or stage II-III showed no significant difference. CONCLUSION: TS was associated with improved RFS and OS in patients with solitary ICC even after PSM. TS may be preferred particularly in patients with tumor stage I and tumor size ≥3 cm.

Clinical Characteristics of Coronavirus Disease 2019 in China.

BACKGROUND: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).

Copper-Catalyzed Direct Allenylation of Inactive Cyclic Ethers.

We report here a direct allenylation reaction of inactive cyclic ethers. The reaction proceeds through a copper-catalyzed 1,4-difunctionalization of 1,3-enynes, with cyano group installed at the allenes simultaneously. This methodology shows a broad functional group compatibility to 1,3-enynes. Diversified allene-modified cyclic ether derivatives were synthesized with high regioselectivity under mild conditions.

Multiple acid-base and electrolyte disturbances upregulate NBCn1, NBCn2, IRBIT and L-IRBIT in the mTAL.

KEY POINTS: The roles of the Na+ /HCO3- cotransporters NBCn1 and NBCn2 as well as their activators IRBIT and L-IRBIT in the regulation of the mTAL transport of NH4+ , HCO3- , and NaCl are investigated. Dietary challenges of NH4 Cl, NaHCO3 or NaCl all increase the abundance of NBCn1 and NBCn2 in the outer medulla. The three challenges generally produce parallel increases in the abundance of IRBIT and L-IRBIT in the outer medulla. Both IRBIT and L-IRBIT powerfully stimulate the activities of the mTAL isoforms of NBCn1 and NBCn2 as expressed in Xenopus oocytes. Our findings support the hypothesis that NBCn1, NBCn2, IRBIT and L-IRBIT appropriately promote NH4+ shunting but oppose HCO3- and NaCl reabsorption in the mTAL, and thus are at the nexus of the regulation pathways for multiple renal transport processes. ABSTRACT: The medullary thick ascending limb (mTAL) plays a key role in urinary acid and NaCl excretion. NBCn1 and NBCn2 are present in the basolateral mTAL, where NBCn1 promotes NH4+ shunting. IRBIT and L-IRBIT (the IRBITs) are two powerful activators of certain acid-base transporters. Here we use western blotting and immunofluorescence to examine the effects of multiple acid-base and electrolyte disturbances on expression of NBCn1, NBCn2 and the IRBITs in rat kidney. We also use electrophysiology to examine the functional effects of IRBITs on NBCn1 and NBCn2 in Xenopus oocytes. NH4 Cl-induced metabolic acidosis (MAc) substantially increases protein expression of NBCn1 and NBCn2 in the outer medulla (OM) of rat kidney. Surprisingly, NaHCO3 -induced metabolic alkalosis (MAlk) and high-salt diet (HSD) also increase expression of NBCn1 and NBCn2 (effect of NaHCO3  > HSD). Moreover, all three challenges generally increase OM expression of the IRBITs. In Xenopus oocytes, the IRBITs substantially increase the activities of NBCn1 and NBCn2. We propose that upregulation of basolateral NBCn1 and NBCn2 plus the IRBITs in the mTAL: (1) promotes NH4+ shunting by increasing basolateral HCO3- uptake to neutralize apical NH4+ uptake during MAc; (2) inhibits HCO3- reabsorption during MAlk by opposing HCO3- efflux via the basolateral anion exchanger AE2; and (3) inhibits NaCl reabsorption by mediating (with AE2) net NaCl backflux into the mTAL cell during HSD. Thus, NBCn1, NBCn2 and the IRBITs are at the nexus of the regulatory pathways for multiple renal transport processes.

Wet- versus dry-suction techniques for endoscopic ultrasound-guided fine-needle aspiration of solid lesions: a multicenter randomized controlled trial.

BACKGROUND: The optimal sampling techniques for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) remain unclear and have not been standardized. The aim of this study was to compare the wet-suction and dry-suction techniques for sampling solid lesions in the pancreas, mediastinum, and abdomen. METHODS: This was a multicenter, crossover, randomized controlled trial with randomized order of sampling techniques. The 296 consecutive patients underwent EUS-FNA with 22G needles and were randomized in a ratio of 1:1 into two separate groups that received the dry-suction and wet-suction techniques in a different order. The primary outcome was to compare the histological diagnostic accuracy of dry suction and wet suction for malignancy. The secondary outcomes were to compare the cytological diagnostic accuracy and specimen quality. RESULTS: Among the 269 patients with pancreatic (n = 161) and non-pancreatic (n = 108) lesions analyzed, the wet-suction technique had a significantly better histological diagnostic accuracy (84.9 % [95 % confidence interval (CI) 79.9 % - 89.0 %] vs. 73.2 % [95 %CI 67.1 % - 78.7 %]; P = 0.001), higher specimen adequacy (94.8 % vs. 78.8 %; P < 0.001), and less blood contamination (P < 0.001) than the dry-suction technique. In addition, sampling non-pancreatic lesions with two passes of wet suction provided a histological diagnostic accuracy of 91.6 %. CONCLUSIONS: The wet-suction technique in EUS-FNA generates better histological diagnostic accuracy and specimen quality than the dry-suction technique. Furthermore, sampling non-pancreatic lesions with two passes of EUS-FNA with wet suction may provide a definitive histological diagnosis when rapid on-site evaluation is not routinely available.

lncRNA CCAT1 is a biomarker for the proliferation and drug resistance of esophageal cancer via the miR-143/PLK1/BUBR1 axis.

Recent evidence indicates that long noncoding RNA colon cancer-associated transcript-1 (lncRNA CCAT1) is abundantly expressed in esophageal cancer and is closely related to the occurrence, development, invasion, metastasis, and drug resistance of this disease. However, the role and molecular mechanisms of CCAT1 in the cell proliferation and chemoresistance of esophageal cancer are largely unknown. The correlation between CCAT1 expression and drug resistance to cisplatin (CDDP) in esophageal squamous cell carcinoma (ESCC) cells was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and quantitative real-time polymerase chain reaction (qRT-PCR) assays. CCAT1 knockdown and miR-143 overexpression or inhibition were used to verify the effects on proliferation and drug resistance via MTT, western blotting, flow cytometry, and immunofluorescence assays. qRT-PCR and western blotting were applied to detect the potential regulatory relationship among CCAT1, miR-143, PLK1, and BUBR1. A xenograft tumor assay was performed to validate the role of CCAT1 in vivo. The expression of CCAT1 was positively correlated with drug resistance in several ESCC cell lines. CCAT1 knockdown and miR-143 overexpression inhibited cell proliferation and CDDP drug resistance. Moreover, the downstream target of CCAT1 was found to be miR-143, which can regulate the expression of PLK1 and BUBR1. In vivo assays showed that CCAT1 knockdown suppressed tumor growth and enhanced the sensitivity of tumors to CDDP in nude mice. Taken together, we discovered a novel mechanism by which CCAT1 promotes cell proliferation and enhances drug resistance by regulating the miR-143/PLK1/BUBR1 signaling axis both in vitro and in vivo. Our findings further suggest that lncRNA CCAT1 may be a potential therapeutic target for overcoming chemoresistance in esophageal cancer.

Removal of Waterborne Pathogen by Nanomaterial-Membrane Coupling System.

The waterborne pathogenic viruses threaten human health. And the nanomaterial-membrane coupling system is promising in virus removal. In this study, phage MS2 was selected as the model virus to investigate the removal of virus with the coupling system. Results revealed that commercial nano TiO2 (Degussa Aeroxide P25) showed both of excellent adsorption and photocatalysis performance for virus removal compared with nano ZnO, nano Fe3O4, carbon nanotube, graphene, nano Ni and Nano TiO2 (anatase). In P25 photocatalysis process, the removal efficiency of phage MS2 increased with the increase of P25 concentration (0~1000 mg L-1), virus initial concentration (102~106 PFU mL-1), UV irradiation doses (5~120 mJ cm-2) and UV light intensity (0.126~0.742 mW cm-2). However, when the P25 concentration increased to over 1000 mg L-1, the virus removal efficiency would remain stable with the increase of P25 concentration. The nanomaterial-membrane coupling system showed excellent performance for virus removal, which was mainly attributed to the adsorption and photocatalysis of P25, and the intercept of membrane. When the P25 concentration was 100 mg L-1, UV irradiation dose was 20 mJ cm-2 and transmembrane pressure was 20 kPa, the phage MS2 removal efficiency could be up to 100%.

Na+/HCO3- Cotransporter NBCn2 Mediates HCO3- Reclamation in the Apical Membrane of Renal Proximal Tubules.

The kidney maintains systemic acid-base balance by reclaiming from the renal tubule lumen virtually all HCO3- filtered in glomeruli and by secreting additional H+ to titrate luminal buffers. For proximal tubules, which are responsible for about 80% of this activity, it is believed that HCO3- reclamation depends solely on H+ secretion, mediated by the apical Na+/H+ exchanger NHE3 and the vacuolar proton pump. However, NHE3 and the proton pump cannot account for all HCO3- reclamation. Here, we investigated the potential contribution of two variants of the electroneutral Na+/HCO3- cotransporter NBCn2, the amino termini of which start with the amino acids MCDL (MCDL-NBCn2) and MEIK (MEIK-NBCn2). Western blot analysis and immunocytochemistry revealed that MEIK-NBCn2 predominantly localizes at the basolateral membrane of medullary thick ascending limbs in the rat kidney, whereas MCDL-NBCn2 localizes at the apical membrane of proximal tubules. Notably, NH4Cl-induced systemic metabolic acidosis or hypokalemic alkalosis downregulated the abundance of MCDL-NBCn2 and reciprocally upregulated NHE3 Conversely, NaHCO3-induced metabolic alkalosis upregulated MCDL-NBCn2 and reciprocally downregulated NHE3 We propose that the apical membrane of the proximal tubules has two distinct strategies for HCO3- reclamation: the conventional indirect pathway, in which NHE3 and the proton pump secrete H+ to titrate luminal HCO3-, and the novel direct pathway, in which NBCn2 removes HCO3- from the lumen. The reciprocal regulation of NBCn2 and NHE3 under different physiologic conditions is consistent with our mathematical simulations, which suggest that HCO3- uptake and H+ secretion have reciprocal efficiencies for HCO3- reclamation versus titration of luminal buffers.

Molecular cloning and characterization of pseudorabies virus EP0 gene.

The pseudorabies virus (PRV) early protein EP0 is a homologue of the herpes simplex virus 1 (HSV-1) immediate-early protein ICP0, which is a multifunctional protein and important for HSV-1 infection. However, the exact function of EP0 is not clear. In this study, using polymerase chain reaction, a 1,104 base-pair sequence of the EP0 gene was amplified from the PRV Becker strain genome and identification of the EP0gene was confirmed by further cloning and sequencing. Bioinformatics analysis indicated that the PRV EP0 gene encoded a putative polypeptide with 367 amino acids. The encoded protein, designated as EP0 contained a conserved RING-finger superfamily domain and was found to be closely related with the herpes virus RING-finger superfamily and was highly conserved among the counterparts encoded by RING-finger genes. Multiple nucleic acid sequence and amino-acid sequence alignments suggested that PRV EP0 showed a relatively higher similarity with EP0-like proteins of genus Varicellovirus than with those of other genera of Alphaherpesvirinae. In addition, phylogenetic analysis showed that PRV EP0 had a close evolutionary relationship with members of genus Varicellovirus, especially bovine herpesvirus 1 (BoHV-1) and BoHV-5. Antigen prediction indicated that several potential B-cell epitopes were located in EP0. Also, subcellular localization analysis demonstrated that EP0 was predominantly localized in the nucleus, suggesting that it might function as a nuclear-targeted protein.

Liver resection versus microwave ablation for solitary and small (≤ 3 cm) HCC with early recurrence in different stages of liver cirrhosis: A propensity score matching study.

BACKGROUND: This study aimed to compare the effectiveness of liver resection (LR) and microwave ablation (MWA) in hepatocellular carcinoma (HCC) patients with early recurrence and varying stages of cirrhosis. METHOD: This study analyzed patients with HCC who underwent hepatectomy and experienced early tumor recurrence (≤3 cm) between December 2002 and December 2020 at the Tongji Hospital. Treatment effectiveness was assessed using a propensity score matching (PSM) analysis. RESULTS: This study included 295 patients (106, LR; 189, MWA), 86 patients in each of the 2 groups were chosen for further comparison, after PSM. After PSM, both LR and MWA demonstrated similar recurrence-free survival (RFS) and overall survival (OS) rates (p = 0.060 and p = 0.118, respectively). However, the LR group had more treatment-related complications. In patients with moderate or severe cirrhosis, no significant differences in RFS or OS rates were found between the LR and MWA groups (p = 0.779 and p = 0.772, respectively). In patients without cirrhosis or with mild cirrhosis, LR showed better RFS and OS rates than MWA (p = 0.024 and p = 0.047, respectively). Multivariate analysis after PSM identified moderate or severe cirrhosis and recurrence intervals ≤12 months as independent predictors of poor RFS and OS in patients with early recurrence of HCC. CONCLUSION: LR is more effective than MWA for early recurrence of HCC in patients without cirrhosis or with mild cirrhosis, showing improved RFS and OS rates. In patients with moderate or severe cirrhosis, the OS and RFS were statistically equal between the two therapies. However, MWA may be preferred owing to its low complication rate.

ADAM17 is overexpressed in non-small cell lung cancer and its expression correlates with poor patient survival.

The purpose of this study was to assess ADAM17 expression and to explore its contribution to the non-small cell lung cancer (NSCLC). Real-time quantitative reverse transcriptase-polymerase chain reaction was conducted to detect ADAM17 mRNA expression. In addition, ADAM17 expression was analyzed by immunohistochemistry in 124 clinicopathologically characterized NSCLC cases. The correlation of ADAM17 expression with patients' survival rate was assessed by Kaplan-Meier and Cox regression. The expression levels of ADAM17 mRNA and protein in NSCLC tissues were both significantly higher than those in non-cancerous tissues. In addition, high expression of ADAM17 was significantly correlated with tumor grade (P=0.026), tumor size (P=0.001), clinical stage (P=0.016), and lymph node metastases (P<0.001). Furthermore, multivariate analysis suggested that tumor grade, tumor size, clinical stage, lymph node metastases, and ADAM17 expression were independent prognostic indicators for NSCLC. Our data suggest for the first time that the increased expression of ADAM17 in NSCLC is associated significantly with aggressive progression and poor prognosis. ADAM17 may be an important molecular marker for predicting the carcinogenesis, progression, and prognosis of NSCLC.

High expression of JMJD6 predicts unfavorable survival in lung adenocarcinoma.

The upregulated expression of JMJD6 was observed in various human cancers. However, little was known about JMJD6 expression and its clinicopathological significance in lung adenocarcinoma. The aim of this study was to investigate the expression and significance of JMJD6 in lung adenocarcinoma progression and prognosis. The levels of JMJD6 mRNA and protein in lung adenocarcinoma specimens and corresponding non-tumorous lung tissues were evaluated by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot. In order to investigate the correlations between JMJD6 and the clinicopathological features of lung adenocarcinoma, the expression of JMJD6 in 154 patients with lung adenocarcinoma was detected by immunohistochemistry. By qRT-PCR and Western blot, the relative expression levels of JMJD6 mRNA and protein were significantly higher in lung adenocarcinoma tissues than in corresponding non-tumorous lung tissues (P < 0.001). Immunohistochemical staining revealed that high JMJD6 expression was closely correlated with tumor size (P = 0.005), pathological grade (P = 0.003), pT status (P = 0.012), pN status (P = 0.003), and pleural invasion (P < 0.001). Moreover, the results of Kaplan-Meier analysis indicated that a high expression level of JMJD6 resulted in a significantly poor prognosis of lung adenocarcinoma patients. Multivariate analysis showed that the status of JMJD6 expression was an independent prognostic factor for lung adenocarcinoma patients. Our results showed that JMJD6 plays a key role in lung adenocarcinoma and therefore may provide an opportunity for developing a novel therapeutic target as well as a prognostic marker in lung adenocarcinoma.

[Changes of Th1/Th2 cytokines in immunocompetent patients with pulmonary cryptococcosis].

OBJECTIVE: To study the changes of Th1/Th2 cytokines in immunocompetent patients with pulmonary cryptococcosis (PC). METHODS: Twenty immunocompetent patients with PC were identified by histopathological examination and enrolled along with the age- and gender-matched healthy controls. The serum concentrations of interferon-γ (IFN-γ), interleukin-4 (IL-4) and interleukin-12 (IL-12) were measured by enzyme linked immunosorbent assay (ELISA). Peripheral blood mononuclear cells (PBMC) in both groups were isolated and incubated with or without recombinant human IL-12 (rhIL-12) for 48 hours, and the concentrations of IFN-γ and IL-4 in the supernatant were measured by ELISA. RESULTS: (1) Serum IFN-γ levels were significantly decreased in the patients compared with the control group [(14.5 ± 2.7) vs (81.8 ± 9.8) ng/L (t = 6.590, P < 0.01)], while no significant difference was observed in serum IL-12 and IL-4 levels [(2.5 ± 0.5) vs (2.52 ± 0.6) ng/L and (6.9 ± 1.3) vs (7.3 ± 1.5) ng/L, (t = 0.0035 and 0.2136, P > 0.05) ]. (2) The concentrations of IFN-γ and IL-4 in the supernatant of PBMC without rhIL-12 stimulation showed no differences between the 2 groups [(55.7 ± 13.6) vs (51.1 ± 17.5) ng/L and (5.1 ± 0.7) vs (5.0 ± 0.6) ng/L (t = 0.2979 and 0.0325, P > 0.05) ]. (3) Treatment with rhIL-12 stimulated the release of IFN-γ, but the increase in the patients [(4.3 ± 0.5) folds] was less compared with that in the controls [(7.9 ± 1.1) folds] (t = 3.01, P < 0.01) , while IL-4 concentration in the supernatant of PBMC was not increased in both groups[ (0.9 ± 0.4) vs (1.3 ± 0.4) folds (t = 0.7240, P > 0.05) ]. CONCLUSIONS: Serum Th1 cytokine (IFN-γ) levels may be dampened in immunocompetent patients with PC, without significant change in serum levels of Th2 cytokines (IL-4). Deficiency in the response to IL-12 stimulation of Th1 cells may be one of the underlying mechanisms for the decline in serum IFN-γ levels.

Postoperative adjuvant tyrosine kinase inhibitors combined with anti-PD-1 antibodies improves surgical outcomes for hepatocellular carcinoma with high-risk recurrent factors.

Background: The clinical value of postoperative adjuvant therapy (PAT) for hepatocellular carcinoma (HCC) remains unclear. This study aimed to explore the effect of PAT with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies on the surgical outcomes of HCC patients with high-risk recurrent factors (HRRFs). Methods: HCC patients who underwent radical hepatectomy at Tongji Hospital between January 2019 and December 2021 were retrospectively enrolled, and those with HRRFs were divided into PAT group and non-PAT group. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups after propensity score matching (PSM). Prognostic factors associated with RFS and OS were determined by Cox regression analysis, and subgroup analysis was also conducted. Results: A total of 250 HCC patients were enrolled, and 47 pairs of patients with HRRFs in the PAT and non-PAT groups were matched through PSM. After PSM, the 1- and 2-year RFS rates in the two groups were 82.1% vs. 40.0% (P < 0.001) and 54.2% vs. 25.1% (P = 0.012), respectively. The corresponding 1- and 2-year OS rates were 95.4% vs. 69.8% (P = 0.001) and 84.3% vs. 55.5% (P = 0.014), respectively. Multivariable analyses indicated that PAT was an independent factor related to improving RFS and OS. Subgroup analysis demonstrated that HCC patients with tumor diameter > 5 cm, satellite nodules, or vascular invasion could significantly benefit from PAT in RFS and OS. Common grade 1-3 toxicities, such as pruritus (44.7%), hypertension (42.6%), dermatitis (34.0%), and proteinuria (31.9%) were observed, and no grade 4/5 toxicities or serious adverse events occurred in patients receiving PAT. Conclusions: PAT with TKIs and anti-PD-1 antibodies could improve surgical outcomes for HCC patients with HRRFs.

Repeat hepatectomy versus microwave ablation for solitary and small (≤3 cm) recurrent hepatocellular carcinoma with early or late recurrence: A propensity score matched study.

BACKGROUND: Repeat hepatectomy (RH) and microwave ablation (MWA) are frequently used procedures for the treatment of recurrent hepatocellular carcinoma (HCC) after curative resection. This study aimed to compare the long-term outcomes of RH and MWA for solitary and small HCC with early or late recurrence. METHOD: This retrospective study enrolled patients who underwent RH or MWA for solitary and small (≤3 cm) recurrent HCC at Tongji hospital between April 2006 and December 2020. Propensity score matching (PSM) was further employed to analyze the prognosis of different treatment methods. RESULTS: A total of 256 patients were analyzed, of whom 94 and 162 underwent RH and MWA, respectively. The overall treatment-related complication rate was higher in the RH group. Both recurrence-free survival (RFS) and overall survival (OS) rates of RH were significantly better than those of MWA. Multivariate analysis showed that MWA, early recurrence (within 24 months after initial resection), cirrhosis, and AFP >400 ng/ml were independent risk factors for poor prognoses of recurrent HCC. The stratified analysis demonstrated that MWA and RH had similar long-term outcomes in patients with early recurrence. Nevertheless, MWA had worse RFS and OS than RH in patients with late recurrence. The same results were obtained in the PSM analysis. CONCLUSION: The long-term outcomes of HCC patients with late recurrence were significantly better than those with early recurrence. RH should be the first choice for solitary small recurrent HCC patients with late recurrence, while MWA should be selected for those with early recurrence.

[Research of xuebijing injection combined with glucocorticoid in treating dermatitis medicamentosa like of trichloroethylene with systemic inflammatory response syndrome].

OBJECTIVE: To study the better efficacy of clinic treatment for dermatitis medicamentosa like of trichloroethylene (DMLT) and observe the clinic efficacy of Xuebejing injection for DMLT patients with systemic inflammatory response syndrome (SIRS). METHODS: 16 DMLT patients with SIRS were randomly divided into control group (conventional therapy) and xuebijing group (conventional therapy plus xuebijing). We evaluated all the patients with APACHE II before treatment and checked the TNF-alpha in blood at the different time (before treatment and the 7th day of treatment). The total usages, first dosage of medrol and the time of therapy for each group were counted. RESULTS: All patients were cured, there was no significant difference according to APACHE II and TNF-alpha before treatment in two groups . The level of TNF-alpha of all the patients were decreased markedly, but more significantly in xuebijing group (P < 0.01). Moreover, the treatment group patients were given relatively less total usages, first dosage of medrol and time of therapy (P < 0.01). CONCLUSION: Xuebejing injection combined glucocorticoids can cure DMLT patients with SIRS effectively, and reduce the total usages, first dosage of medrol and time of therapy.

Copper-Catalyzed Aminoarylation of Alkenes via Aminyl Radical Addition and Aryl Migration.

We describe a new strategy for aminoarylation of alkenes by copper-catalyzed smiles rearrangement using O-benzoylhydroxylamines as the amine reagent. This method affords various ß-amino amide derivatives possessing a quaternary carbon center with wide functional group tolerance and high regioselectivity. The mechanistic studies indicate that the transformation can involve aminyl radical intermediates under acid-free condition.

Machine learning predicts portal vein thrombosis after splenectomy in patients with portal hypertension: Comparative analysis of three practical models.

BACKGROUND: For patients with portal hypertension (PH), portal vein thrombosis (PVT) is a fatal complication after splenectomy. Postoperative platelet elevation is considered the foremost reason for PVT. However, the value of postoperative platelet elevation rate (PPER) in predicting PVT has never been studied. AIM: To investigate the predictive value of PPER for PVT and establish PPER-based prediction models to early identify individuals at high risk of PVT after splenectomy. METHODS: We retrospectively reviewed 483 patients with PH related to hepatitis B virus who underwent splenectomy between July 2011 and September 2018, and they were randomized into either a training (n = 338) or a validation (n = 145) cohort. The generalized linear (GL) method, least absolute shrinkage and selection operator (LASSO), and random forest (RF) were used to construct models. The receiver operating characteristic curves (ROC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were used to evaluate the robustness and clinical practicability of the GL model (GLM), LASSO model (LSM), and RF model (RFM). RESULTS: Multivariate analysis exhibited that the first and third days for PPER (PPER1, PPER3) were strongly associated with PVT [odds ratio (OR): 1.78, 95% confidence interval (CI): 1.24-2.62, P = 0.002; OR: 1.43, 95%CI: 1.16-1.77, P < 0.001, respectively]. The areas under the ROC curves of the GLM, LSM, and RFM in the training cohort were 0.83 (95%CI: 0.79-0.88), 0.84 (95%CI: 0.79-0.88), and 0.84 (95%CI: 0.79-0.88), respectively; and were 0.77 (95%CI: 0.69-0.85), 0.83 (95%CI: 0.76-0.90), and 0.78 (95%CI: 0.70-0.85) in the validation cohort, respectively. The calibration curves showed satisfactory agreement between prediction by models and actual observation. DCA and CIC indicated that all models conferred high clinical net benefits. CONCLUSION: PPER1 and PPER3 are effective indicators for postoperative prediction of PVT. We have successfully developed PPER-based practical models to accurately predict PVT, which would conveniently help clinicians rapidly differentiate individuals at high risk of PVT, and thus guide the adoption of timely interventions.