Control over Berry Curvature Dipole with Electric Field in WTe_{2}.

Berry curvature dipole plays an important role in various nonlinear quantum phenomena. However, the maximum symmetry allowed for nonzero Berry curvature dipole in the transport plane is a single mirror line, which strongly limits its effects in materials. Here, via probing the nonlinear Hall effect, we demonstrate the generation of Berry curvature dipole by applied dc electric field in WTe_{2}, which is used to break the symmetry constraint. A linear dependence between the dipole moment of Berry curvature and the dc electric field is observed. The polarization direction of the Berry curvature is controlled by the relative orientation of the electric field and crystal axis, which can be further reversed by changing the polarity of the dc field. Our Letter provides a route to generate and control Berry curvature dipole in broad material systems and to facilitate the development of nonlinear quantum devices.

Apatinib combined with SOX regimen for conversion therapy in advanced gastric cancer patients: a retrospective cohort study.

BACKGROUND: Recently, many studies have shown that the progress of conversion therapy can provide surgical opportunities for patients with advanced gastric cancer (GC) and bring survival benefits. However, the results of the current study show that the regimen used in conversion therapy is still controversial. Apatinib, as the standard third-line treatment for GC, has an inconclusive status in conversion therapy. METHODS: This study retrospectively analyzed GC patients admitted to Zhejiang Provincial People's Hospital from June 2016 to November 2019. All patients were pathologically diagnosed, had unresectable factors, and received SOX regimen with or without apatinib as conversion therapy. RESULTS: A total of 50 patients were enrolled in the study. Altogether 33 patients (66%) received conversion surgery and 17 patients (34%) received conversion therapy without surgery. The median progression-free survival (PFS) between surgery group and non-surgery group were 21.0 versus 4.0 months (p < 0.0001), and the median overall survival (OS) were 29.0 versus 14.0 months (p < 0.0001). In conversion surgery group, 16 patients (16/33) were treated with SOX plus apatinib, and the R0 resection rate was 81.3%; 17 patients (17/33) were treated with SOX regimen along, and the R0 resection rate was 41.2% (p = 0.032). The PFS in the SOX combined with apatinib group was significantly longer than that of SOX group (25.5 versus 16 months, p = 0.045), and the median OS were 34.0 versus 23.0 months (p = 0.048). The addition of apatinib did not increase the incidence of serious adverse reactions throughout the preoperative therapy period. CONCLUSIONS: Patients with advanced inoperable gastric cancer could benefit probably from conversion chemotherapy and subsequence conversion surgery. Apatinib-targeted therapy combined with SOX chemotherapy may be a safe and feasible option for conversion therapy.

Rhodomeroterpene alleviates macrophage infiltration and the inflammatory response in renal tissue to improve acute kidney injury.

Inflammation is broadly recognized as an important factor in the pathogenesis of acute kidney injury (AKI), but pharmacological approaches to alleviate inflammation in AKI have not been proved successful in clinical trials. Macrophage infiltration into renal tissue promotes inflammatory responses that contribute to the pathogenesis of AKI. Suppression of renal tissue inflammatory responses is postulated to improve renal injury of patients and animals. Rhodomeroterpene (RMT) is a novel meroterpenoid isolated from the Rhododendron genus that was shown to exert anti-inflammatory action in vivo or in vitro in this study. We investigated the treatment effects of RMT on LPS-induced sepsis and two different AKI models. The results showed that pretreatment with RMT (30 mg kg-1  d-1 , ip, for 3 days) significantly inhibited acute inflammatory responses in LPS-induced septic mice. In both renal ischemia-reperfusion injury (I/R) and sepsis-induced AKI models, RMT (30 mg kg-1  d-1 , ip, for 3 days) ameliorated renal function and injury and alleviated inflammation by reducing the infiltration of immune cells, including macrophages and neutrophils. Furthermore, our study demonstrated that RMT inhibits inflammatory responses in macrophages. The anti-inflammatory effects of RMT may be due to the inactivation of the IKK/NF-κB and PI3K/PDK1/Akt inflammatory signaling pathways in macrophages. Collectively, our findings indicate that RMT ameliorates renal injury and alleviates the renal inflammatory state in different AKI models, suggesting that RMT may be a potential agent for the treatment of AKI.

Tumor-mutation burden as a marker for immunotherapy of pancreatic cancer: the case report and literature review.

Pancreatic cancer is digestive cancer with limited therapeutic options and a poor outcome. Pancreatic cancer has a high mortality rate, with a 5-year survival rate of less than 5%. The median survival after metastasis of the disease is less than 6 months. Studies have revealed that the standard treatment, including palliative chemotherapy or immunotherapy, is not significantly effective for pancreatic cancer. Herein, we report a case of pancreatic cancer who benefited from a combination of anti-PD-1 immunotherapy and chemotherapy.

An aerobic and green C-H cyanation of terminal alkynes.

This study describes a benign C-H cyanation of terminal alkynes with α-cyanoesters serving as a nontoxic cyanide source. In situ generation of the key copper cyanide intermediate is proposed by a sequence of α-C-H oxidation and copper-mediated ß-carbon elimination of α-cyanoesters, releasing the α-ketoester byproduct observed experimentally. The ensuing reaction of copper cyanide with terminal alkynes delivers preferentially cyanoalkynes and surpasses the possible Glaser type dimerization of terminal alkynes or the undesired accumulation of HCN under protic conditions. The presence of the co-oxidant K2S2O8 is crucial to this selectivity, probably by promoting oxidative transmetalation and the resulting formation of the Cu(iii)(acetylide)(CN) intermediate. All the reagents and salts used are commercially available, cheap and nontoxic, avoiding the use of highly toxic cyanide salts typically required in cyanation studies. The scope of this reaction is demonstrated with a set of alkynes and α-cyanoesters. The application of this method to late-stage functionalization of the terminal alkyne group in an estrone derivative is also feasible, showing its practical value for drug design.

Effect of mandibular advancement device on the stomatognathic system in patients with mild-to-moderate obstructive sleep apnoea-hypopnoea syndrome.

OBJECTIVE: This study was conducted to evaluate the changes of temporomandibular joints (TMJs) through magnetic resonance imaging (MRI) scanning and the electrical changes in mandibular movement and masticatory muscle surface of mild-to-moderate obstructive sleep apnoea-hypopnoea syndrome (OSAHS) patients before and after treatment with mandibular advancement device (MAD). METHODS: This was a single-centre, prospective study recruiting OSAHS patients undergoing treatment with MAD in Department of Stomatology, Yannan Hospital, Kunming, China. Patients were recruited from February 2015 to October 2015, and TMJ changes were observed in MRI scanning before and after 18 months of treatment with MAD in cohort 1. The second cohort of the patients were recruited from January 2014 to September 2015 and electrical changes in mandibular movement and masticatory muscle surface of patients before and after 6 months of treatment with MAD. RESULTS: In the cohort 1, TMJ changes analysed through MRI scanning, before and after 18-month treatment with MAD, there was no significant deviation in the angle of joint disc position. A minor change in the position relationship between condylar process, articular disc and articular fossa but not significant was observed. There was no significant difference in the shape and magnitude of mandibular incision edge movement, percussion movement, masticatory movement and condylar central trajectory among the recruited OSAHS patients, before and after 6 months of MAD treatment as analysed through electromyography. CONCLUSION: In this study, from the results it was evident that the effect of MAD on the stomatognathic system of OSAHS patients is minimal.

Concise Total Synthesis and Antifungal Activities of Fusaric Acid, a Natural Product.

The total synthesis of a natural product alkaloid fusaric acid (FA), which exhibits herbicide, fungicide, insecticide and even diverse notable pharmacological activities, was accomplished in four steps using commercially available materials. The synthesis, based on a unified and flexible strategy using 6-bromonicotinaldehyde as a common intermediate, is concise, convergent, practical and can be carried out on a two-gram scale. This approach could be readily applicable to the synthesis of its analogues. In addition, FA had a wide range of inhibitory activities against 14 plant pathogenic fungi in this study, which demonstrated that as a leading compound, and it has great potential to be further developed as an agricultural fungicide.

Efficacy of regional arterial embolization before pleuropulmonary resection in 32 patients with tuberculosis-destroyed lung.

BACKGROUND: Treatment of tuberculous-destroyed lung (TDL) with pleuropulmonary resection is challenging. Pulmonary hemorrhage is a frequent complication of this surgical procedure. Continuous efforts have been made to investigate clinical procedures that may reduce intraoperative bleeding effectively. In this study, we evaluated the feasibility and safety of regional arterial embolization before pleuropulmonary resection in patients with TDL. METHODS: The clinical data of 32 patients with TDL were retrospectively reviewed and analyzed. These patients were admitted to the hospital between July 2009 and November 2016. All of the patients had moderate to massive hemoptysis and received regional arterial embolization in affected areas. Then, these patients underwent pleuropulmonary resection within 1 week to 2 months after embolization. RESULTS: The results showed that 25 patients (78.1%) had bronchial artery, and all patients had non-bronchial systemic artery found in affected areas. Mild to moderate chest pain was reported in 6 patients, and fever was reported in 2 patients. Intraoperative blood loss during pleuropulmonary resection in patients who had received preoperative regional arterial embolization was 625.6 ± 352.6 ml. Duration of the operation was 120.3 ± 75.2 min. Bronchopleural fistulae and empyema were found in 3 cases (9.4%). CONCLUSION: Performance of regional arterial embolization before pleuropulmonary resection offers a safe and feasible option that reduces intraoperative blood loss and shortens operative time in patients with TDL.

Willingness to Pay for Measures of Managing the Health Effects of Heat Wave in Beijing, China: a Cross-sectional Survey.

OBJECTIVE: There are evidences that heat wave events cause deaths and emergency cases. This article used the contingent valuation method to find the willingness to pay for the protective measures and investigated the factors that influence the willingness to pay. METHODS: A cross-sectional face-to-face household survey was completed by 637 urban long-term residents and 591 rural long-term residents aged 15-79 in Beijing, China. Binary logistic regression was used to identify factors that influenced the payment rate or payment amount for the protective measures, including independent variables for district, gender, age, education, income, air conditioner ownership, heat wave experience, and chronic non-communicable disease. RESULTS: The payment rate was 41.1% for protective measures provided by the government and 39.5% by measures provided by the market. Most of the respondents were willing to pay 40 CNY per capita annually for measures provided by the government or the market. The factors influencing willingness to pay were district, gender, income, air conditioner ownership, heat wave experience, and chronic non-communicable disease.. CONCLUSION: Protective measures for heat waves need to be provided immediately. More attention should be paid to the situation of vulnerable groups, such as people who live in urban areas, those without air conditioning, and those who have experienced a heat wave in the past.

Microfiber-based, highly nonlinear graphene saturable absorber for formation of versatile structural soliton molecules in a fiber laser.

We reported on the generation of versatile soliton molecules in a fiber laser mode-locked by a microfiber-based graphene saturable absorber (GSA). By virtue of the highly nonlinear effect of the microfiber-based GSA, the soliton molecules could be easily observed. In addition to regular soliton molecules, it is found that the "soliton atoms" in molecules could exhibit different characteristics and show ultra-narrow pulse separations, which was termed as 'structural soliton molecule'. The pulse profiles of 'structural soliton molecules' were further reconstructed theoretically. The obtained results would give further insight towards understanding the dynamics of soliton molecules in fiber lasers.

Predictive value of NLR and PLR for immune-related adverse events: a systematic review and meta-analysis.

BACKGROUND: Currently, there is a lack of affordable and accessible indicators that can accurately predict immune-related adverse events (irAEs) resulting from the use of immune checkpoint inhibitors (ICIs). In order to address this knowledge gap, our study explore the potential predictive value of two ratios, namely the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), for irAEs in cancer patients. METHODS: A systematic search was performed in PubMed, Embase, and the Cochrane library. Studies involving NLR or PLR with irAEs were included. Quality and risk of bias of the selected studies were assessed. Forest plots were created based on Cox model analysis. Random effects meta-analyses were conducted to estimate odds ratio (OR) and its 95% confidence interval (CI). RESULTS: After screening 594 studies, a total of 7 eligible studies with 1068 cancer patients were included. Analysis based on Cox regression showed that low neutrophil-lymphocyte ratio (L-NLR) (OR = 3.02, 95% CI 1.51 to 6.05, P = 0.002) and low platelet-lymphocyte ratio (L-PLR) (OR = 1.83, 95% CI 1.21 to 2.76, P = 0.004) were associated with irAEs. In the subgroup analysis of cut-off value, when the NLR cut-off value was 3, irAEs was significantly correlated with NLR (OR = 2.63, 95% CI 1.63 to 4.26, P < 0.001). CONCLUSIONS: Both L-NLR and L-PLR have been found to be significantly associated with irAEs. Consequently, patients identified as being at a higher risk for irAEs should be subjected to more diligent monitoring and close observation.

Efficacy of Dan'e Fukang Soft Extract in Moderate Ovarian Hyperstimulation Syndrome for Concurrent Treatment of Blood and Fluid Guided by the "Triple Prevention" Principle.

Objective: This study aimed to evaluate the therapeutic efficacy and safety of Dan'e Fukang soft extracts in moderate ovarian hyperstimulation syndrome (OHSS) for the simultaneous treatment of blood and fluid, guided by the traditional Chinese medicine principle of "triple prevention". Methods: This study conducted a retrospective analysis of clinical data from outpatients who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection embryo transfer (ICSI-ET). A total of 2245 cases were included and divided into a treatment group (1002 cases) and a control group (1243 cases). Patients in the treatment group were administered Dan'e Fukang soft extracts orally in addition to conventional Western medicine. Comparative assessments were made between the two groups on pelvic ascites volume, maximum ovary diameter, dysmenorrhea incidence post-oocyte retrieval, and safety indicators. Results: There were no statistically significant differences between the treatment group and the control group in terms of general characteristics or the levels of follicle-stimulating hormone (FSH), luteotropic hormone (LH), estradiol (E2), or progesterone (P) at the time of gonadotropin (Gn) initiation. The groups did not differ significantly when we compared the levels of LH, E2, or P on the day of human chorionic gonadotropin (hCG) injection and during ovarian hyperstimulation protocols (P > 0.05 for all indicators). The differences in the volume of pelvic ascites, the maximum ovarian diameter, and the incidence of dysmenorrhea after oocyte retrieval were statistically significant between the treatment group and the control group (P < 0.05 in both). There were no instances of adverse reactions in either group. Conclusion: Based on the traditional Chinese medicine principle of "triple prevention", the use of Dan'e Fukang soft extracts for the simultaneous treatment of blood and fluid in moderate OHSS significantly improved the absorption of pelvic ascites, promoted ovarian recovery, and reduced the incidence of dysmenorrhea after oocyte retrieval.

Aggregation-Induced Emission CN-Based Nanoparticles to Alleviate Hypoxic Liver Fibrosis via Triggering HSC Ferroptosis and Enhancing Photodynamic Therapy.

Hypoxia can lead to liver fibrosis and severely limits the efficacy of photodynamic therapy (PDT). Herein, carbon nitride (CN)-based hybrid nanoparticles (NPs) VPSGCNs@TSI for light-driven water splitting were utilized to solve this problem. CNs were doped with selenide glucose (Se-glu) to enhance their red/NIR region absorption. Then, vitamin A-poly(ethylene glycol) (VA-PEG) fragments and aggregation-induced emission (AIE) photosensitizers TSI were introduced into Se-glu-doped CN NPs (VPSGCNs) to construct VPSGCNs@TSI NPs. The introduction of VA-PEG fragments enhanced the targeting of the NPs to activated hepatic stellate cells (HSCs) and reduced their toxicity to ordinary liver cells. VPSGCN units could trigger water splitting to generate O2 under 660 nm laser irradiation, improve the hypoxic environment of the fibrosis site, downregulate HIF-1α expression, and activate HSC ferroptosis via the HIF-1α/SLC7A11 pathway. In addition, generated O2 could also increase the reactive oxygen species (ROS) production of TSI units in a hypoxic environment, thereby completely reversing hypoxia-triggered PDT resistance to enhance the PDT effect. The combination of water-splitting materials and photodynamic materials showed a 1 + 1 > 2 effect in increasing oxygen levels in liver fibrosis, promoting ferroptosis of activated HSCs and reversing PDT resistance caused by hypoxia.

Third-line treatment options in metastatic pancreatic cancer patients: a real-world study.

Background: There are currently no standard therapy regimens for the third-line treatment of metastatic pancreatic cancer (mPC) patients. The aim of the present study was to compare the efficacy and safety of different third-line therapy regimens for mPC in the real-world. Methods: This study retrospectively analyzed mPC patients admitted to Zhejiang Provincial People's Hospital between June 2013 and January 2023. All patients' diagnoses were pathologically confirmed and their treatment was continued after the second-line therapy failed. The primary study endpoints included median overall survival (mOS), median progression-free survival (mPFS), and disease control rate (DCR). Results: A total of 72 patients were enrolled in the study. Of these, 36 patients received chemotherapy alone, 16 received chemotherapy combined with targeted therapy or immunotherapy, 14 received chemotherapy-free antitumor therapy, and six received palliative care. The mPFS value for these groups was 4.40 months, 5.20 months, 2.33 months, and 0.80 months, respectively. The mOS value was 6.90 months, 5.90 months, 3.33 months, and 0.80 months, respectively. The DCR was 33.4%, 31.3%, 21.4%, and 0.0%, respectively. Overall, there were significant differences in prognosis between the palliative care group and the other treatment groups (mOS, P < 0.001; mPFS P < 0.001; DCR, P < 0.001). The differences among the mPFS, mOS, and DCR for different antitumor therapy regimens were not statistically significant. Compared to the chemotherapy alone group, the chemotherapy combined with targeted therapy or immunotherapy group experienced more adverse events (100% vs. 75.0%; P = 0.002). Chemotherapy combined with targeted therapy or immunotherapy was associated with a higher risk of grade 3/4 hyperaminotransferemia compared to chemotherapy alone (31.3% vs. 0.0%; P = 0.020) and chemotherapy-free antitumor therapy (31.3% vs. 0.0%; P = 0.020). Conclusions: Third-line antitumor therapy can prolong the survival time of patients with mPC. Targeted therapy or immunotherapy failed to further improve survival benefits based on chemotherapy results. Patients who underwent the third-line treatment with good physical status and family history of cancer were independent prognostic factors for longer mOS. The sequencing of fluorouracil and gemcitabine in the front-line therapy did not affect third-line mOS.

Acute aortic dissection caused by fruquintinib for metastatic colorectal cancer-a case report and literature review.

Background: Fruquintinib is a highly selective tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR). At present, it has been approved for third-line therapy for advanced metastatic colorectal cancer in China. Like other small-molecule tyrosine kinase inhibitors, adverse reactions such as hand-foot syndrome, hypertension and cardiotoxicity may be seen. However, acute aortic dissection caused by fruquintinib has not been reported so far. Case Description: Here, we report a case of aortic dissection. The patient, a 61-year-old man with advanced metastatic colorectal cancer, without history of hypertension or other risk factors for aortic dissection, received fruquintinib as the third line of treatment. Six weeks after oral fruquintinib treatment, the patient developed acute aortic dissection, and the occurrence of the adverse effect was determined to be probably related to the use of fruquintinib. This article focuses on the potential pathogenesis of fruquintinib-induced active dissection. Conclusions: We reported the first case of fruquintinib-associated aortic dissection, and discussed the possible mechanism of vascular endothelial growth factor (VEGF)-VEGFR signal pathway (VSP) inhibitors leading to aortic dissection. As a new drug, fruquintinib brings not only clinical benefits, but also brings some adverse reactions. Clinicians must be vigilant to the cardiovascular toxicity caused by small molecular tyrosine kinase inhibitors, especially the severe cardiovascular toxicity, and strengthen monitoring and management.

Correlation between methylenetetrahydrofolate reductase gene-specific methylation and recurrent spontaneous abortion.

OBJECTIVE: To investigate the correlation between methylenetetrahydrofolate reductase (MTHFR) gene-specific methylation and recurrent spontaneous abortion (RSA). METHODS: A total of 50 RSA patients who visited our hospital were recruited in the study group; 50 multiparous women who underwent physical examinations during the same period were enrolled in the control group. The levels of homocysteine, folic acid, and vitamin B12 and their MTHFR gene polymorphism and specific methylation were measured in both groups. The Logistic regression equation was used to analyze the correlation between MTHFR gene-specific methylation and RSA. RESULTS: The methylated allele MM was not found in the control group, and the frequency in the study group was 1.19%. The frequency of the MU genotype in the study group 32.93% was higher than that in the control group 12.45%. The frequency of methylated alleles of CC and CT genotypes carrying MTHFR C677T polymorphism in the study group was higher than that in the control group (P < 0.05). There was no significant difference in the TT genotype between the two groups (P > 0.05). Multivariate Logistic regression analysis exhibited that patients with methylated alleles of CC genotype had a risk of RSA increased by 1.167 times, and the risk increased by 2.500 times in patients with methylated alleles of CT genotype (P < 0.05). 83.33% of RSA patients carrying methylated alleles affected hyperhomocysteinemia. In patients with elevated homocysteine levels, the risk of RSA caused by methylated allele was significantly increased by 7.321 times. CONCLUSION: MTHFR gene-specific methylation can significantly increase the risk of RSA.

Comparison of the efficacy and safety of fruquintinib and regorafenib in the treatment of metastatic colorectal cancer: A real-world study.

Background: Fruquintinib and regorafenib have been approved for the third-line therapy of metastatic colorectal cancer (mCRC) in China. However, at present, there is a lack of head-to-head clinical trials on the comparison of efficacy and safety between the two drugs. Materials and methods: The data of patients with mCRC who were treated with fruquintinib or regorafenib after the standard chemotherapy in Zhejiang Provincial People's Hospital from October 2018 to November 2021 were collected and analyzed. The primary endpoints were overall survival (OS), progression-free survival (PFS) and adverse events. The secondary endpoints were the appropriate sequence, objective remission rate (ORR) and disease control rate (DCR) of fruquintinib and regorafenib. Results: A total of 105 patients were enrolled in this study. The ORR of fruquintinib group (n=55) and regorafenib group (n=50) were 6.1% and 2.0%; the DCR were 65.3% and 54.2%, respectively. There was no significant difference in median OS (mOS) and PFS (mPFS) between the two groups (mOS:14.2 vs12.0 months, p=0.057; mPFS:4.4 vs 3.5 months, p=0.150). Combined immunotherapy showed a synergistic effect. The mPFS and mOS of fruquintinib combined with anti-PD-1 therapy were longer than those of fruquintinib monotherapy (mPFS:5.9 vs 3.0 months, p=0.009; mOS:17.5 vs 11.3 months, p=0.008). The mOS of patients treated with regorafenib combined with anti-PD-1 therapy was 14.8 months higher than that of regorafenib monotherapy (p=0.045). When combined with anti-PD-1 therapy, the mPFS and mOS of fruquintinib was significantly longer than regorafenib (mPFS:5.9 vs 3.8 months, p=0.018; mOS:17.5 vs 14.8 months, p=0.044). In the treatment sequence, the OS of patients treated with regorafenib and then fruquintinib was significantly longer than that of the reverse treatment sequence (15.0 vs 8.3 months, p=0.019). The adverse reactions were generally similar, but the incidence of hand-foot syndrome of regorafenib was higher than that of fruquintinib, while fruquintinib was more prone to grade 3 hypertension. Conclusion: Fruquintinib monotherapy showed better disease control rate and objective remission rate in the post-line therapy of metastasis colorectal cancer. Notably, the combination of PD-1 immunotherapy brought the additional effect, especially in the fruquintinib combined with anti-PD-1 therapy. Patients treated with regorafenib and then fruquintinib was significantly longer than that of the reverse treatment sequence. The toxicity of fruquintinib and regorafenib are similar.

Two-photon excited red-green "discoloration" bioprobes for monitoring lipid droplets and lipid droplet-lysosomal autophagy.

Lipid droplets (LDs) and their autophagy by lysosomes are closely related to a variety of physiological and pathological conditions. Therefore, identifying and tracking LDs and the dynamic process of autophagy can provide useful information for the diagnostics and treatment of related diseases. However, few organic small molecule-based fluorescent probes can specifically recognize LDs and dynamically track their autophagy process. Herein, we synthesized a "discoloration" fluorescent bioprobe DPABP-BI with distinguishable features including red fluorescence emission (630 nm), large Stokes shift (145 nm), two-photon excitation and outstanding photostability and biocompatibility. In particular, LDs could be specifically identified via the red fluorescence emission of DPABP-BI (colocalization constant of 0.98), while autophagolysosomes could be visualized via the green fluorescence emission of its acid-hydrolyzed product (colocalization constant of 0.90) to track the autophagy dynamic process. In addition, DPABP-BI enabled the specific recognition of fatty substances in zebrafish larvae. In this study, a two-photon excited red light small molecule probe was constructed to identify LDs and track their autophagy dynamic process by changing the fluorescence emission wavelength.

Light controlled self-escape capability of non-cationic carbon nitride-based nanosheets in lysosomes for hepatocellular carcinoma targeting stimulus-responsive gene delivery.

High positive charge-induced toxicity, easy lysosomal degradation of nucleic acid drugs, and poor lesion sites targeting are major problems faced in the development of gene carriers. Herein, we proposed the concept of self-escape non-cationic gene carriers for targeted delivery and treatment of photocontrolled hepatocellular carcinoma (HCC) with sufficient lysosome escape and multiple response capacities. Functional DNA was bound to the surface of biotin-PEG2000-modified graphitic carbon nitride (Bio-PEG-CN) nanosheets to form non-cationic nanocomplexes Bio-PEG-CN/DNA. These nanocomposites could actively target HCC tissue. Once these nanocomplexes were taken up by tumor cells, the accumulated reactive oxygen species (ROS) generated by Bio-PEG-CN under LED irradiation would disrupt the lysosome structure, thereby facilitating nanocomposites escape. Due to the acidic microenvironment and lipase in the HCC tissue, the reversible release of DNA could be promoted to complete the transfection process. Meanwhile, the fluorescence signal of Bio-PEG-CN could be monitored in real time by fluorescence imaging technology to investigate the transfection process and mechanism. In vitro and in vivo results further demonstrated that these nanocomplexes could remarkably upregulate the expression of tumor suppressor protein P53, increased tumor sensitivity to ROS generated by nanocarriers, and realized effective gene therapy for HCC via loading P53 gene.

[Impact of age and sex on virologic responses of peginterferon alfa-2a and ribavirin treatment in chronic hepatitis C].

OBJECTIVE: To investigate the impact of age and sex on virologic responses rates to peginterferon alfa-2a and ribavirin treatment in patients with chronic hepatitis C. METHODS: The medical records of 449 chronic hepatitis C patients, treated with peginterferon and ribavirin in Department of Infectious Diseases, the Second Affiliated Hospital, Harbin Medical University, were retrospectively analyzed. These patients were divided into three groups according to age: patients < 40 years (n = 131), patients 40 - 50 years (n = 131) and patients > 50 years (n = 187). The virologic response rates, the incidences of side events, and the rates of patients receiving ≥ 80% of planned peginterferon alfa-2a or ribavirin dose were compared between male and female patients in the three groups. The influential factors on sustained virologic response (SVR) of patients were studied by multivariate analysis. RESULTS: For genotype 1, in patients < 40 years group, the SVR rate of female was significantly higher than that of male (75.0%, 30/40 vs 54.0%, 27/50; P < 0.05); in patients 40-50 years group, there was no significant difference in the SVR rate between male and female (51.0%, 25/49 vs 53.7%, 22/41; P > 0.05); in patients > 50 years group, the SVR rate of female was significantly lower than that of male (31.1%, 19/61 vs 50.7%, 34/67; P < 0.05). For genotype 2, there were no significant differences in virologic response rates between male and female in the three groups. The incidence of adverse events of patients aged < 40 years group, 40 - 50 years group, > 50 years group, were 51.1% (67/131), 51.1% (67/131), and 70.6% (132/187), respectively, and the incidence of adverse events of patients aged > 50 years was significantly higher than those of other groups (P < 0.001). For genotype 1, in patients > 50 years group, the rate of patients receiving ≥ 80% of planned ribavirin dose of female was significantly lower than that of male (42.6%, 26/61 vs 62.7%, 42/67; P < 0.05). In multivariate analysis, the independent factors associated with SVR of patients aged > 50 years were sex (P = 0.013), genotypes (P = 0.002), cirrhosis (P = 0.004), ≥ 80% of planned ribavirin dose (P = 0.008) and presence of rapid virologic response (RVR) (P = 0.001). CONCLUSIONS: For genotype 1 patients, in patients < 40 years group the SVR rate of female is higher than that of male; in patients 40 - 50 years group, male and female share similar SVR rates; in patients > 50 years group the SVR rate of female is lower than that of male. Age and sex has no impact on virologic responses rates for genotype 2 patients.