Cost-effectiveness of different intervention strategies of human immunodeficiency virus in Zhejiang, China: a Model Study From 2023 to 2052.

OBJECTIVE: :Mass screening for human immunodeficiency virus (HIV) and preexposure prophylaxis (PrEP) may be effective measures for reducing the probability of HIV transmission. Our study aimed to determine the cost-effectiveness of preliminary screening in the general population, PrEP for HIV-negative spouses in serodiscordant couples, or both approaches in Zhejiang Province. DESIGN: :From a policy-maker's perspective, a Markov model was constructed to compare 4 strategies over a 30-year horizon. METHODS: :In the Markov model, the implementation intensities of the strategies varied from 50% to 100%. Different strategies were evaluated by the reduction of unfavorable clinical outcomes, saved life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and net monetary benefits (NMBs). RESULTS: :The PrEP-Screening strategy reduced the most unfavorable clinical outcomes and saved the most LYs and QALYs from 2023 to 2052. It always gained the maximum QALYs and NMB, while its ICER was always lower than the willingness-to-pay (WTP). The NMB of the PrEP-Screening strategy gradually increased as the implementation intensity increased. CONCLUSIONS: :With adequate manpower and policies, we suggest implementing the PrEP-Screening strategy in Zhejiang Province, suggesting that the broader the population coverage of the strategy, the better. In addition, the PrEP strategy is an alternative.

Computed tomography guided electromagnetic navigation system in percutaneous laser ablation for treating primary lung cancer: a case report.

Background: The majority of patients of lung cancer have already lost the chance of surgery at the time of diagnosis. Percutaneous local thermal ablation is a precise minimally invasive technique and a viable alternative to surgical treatment. Compared with radiofrequency ablation and microwave ablation, percutaneous laser ablation for the treatment of lung tumors is less commonly used and reported, especially for primary lung cancer. Case presentation: A 63-year-old male patient with mixed pulmonary nodules selected computed tomography-guided electromagnetic navigation system for percutaneous biopsy and laser ablation therapy. The puncture point was determined through Computed tomography scanning, along with the placement of the electromagnetic navigation system locators. After rapid on-site evaluation and pathological examination of the puncture tissue specimen, the diagnosis of lung adenocarcinoma was confirmed. A 980-nanometer wavelength semiconductor laser fiber was inserted into the appropriate position guided by the electromagnetic navigation system. Subsequently, a power of 7 watt was applied to ablate the tumor for 30 seconds, then pause for 60 seconds before repeating the procedure. Positron emission tomography-Computed tomography examination was performed 1 month after operation, suggesting complete response of the tumor. Conclusion: Here, we present a case of percutaneous laser ablation treatment for primary lung cancer guided by computed tomography-electromagnetic navigation system. As a more precise, shorter duration, impedance-independent, safe and effective minimally invasive thermal ablation method, it is expected to gain wider application and become a novel alternative for surgical treatment.

[Construction of a risk predictive model of acute kidney injury based on urinary tissue inhibitor of metalloproteinase 2 and insulin-like growth factor-binding protein 7 and its early predictive value in critically ill patients].

OBJECTIVE: To establish a risk predictive model nomogram of acute kidney injury (AKI) in critically ill patients by combining urinary tissue inhibitor of metalloproteinase 2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7), and to verify the predictive value of the model. METHODS: A prospective observational study was conducted. The patients with acute respiratory failure or circulatory disorder admitted to the intensive care unit (ICU) of Northern Jiangsu People's Hospital from November 2017 to April 2020 were enrolled. The patients were enrolled within 24 hours of ICU admission, and their general conditions and relevant laboratory test indicators were collected. At the same time, urine was collected to determine the levels of biomarkers TIMP2 and IGFBP7, and TIMP2×IGFBP7 was calculated. Patients were divided into non-AKI and AKI groups according to whether grade 2 or 3 AKI occurred within 12 hours after enrollment. The general clinical data and urinary TIMP2×IGFBP7 levels of patients between the two groups were compared. The indicators with P < 0.1 in univariate analysis were included in the multivariate Logistic regression analysis to obtain the independent risk factors for grade 2 or 3 AKI within 12 hours in critical patients. An AKI risk predictive model nomogram was established, and the application value of the model was evaluated. RESULTS: A total of 206 patients were finally enrolled, of whom 54 (26.2%) developed grade 2 or 3 AKI within 12 hours of enrollment, and 152 (73.8%) did not. Compared with the non-AKI group, the patients in the AKI group had higher body mass index (BMI), pre-enrollment serum creatinine (SCr), urinary TIMP2×IGFBP7 and proportion of using vasoactive drugs, and additional exposure to AKI (use of nephrotoxic drugs before enrollment) was more common. Multivariate Logistic regression analysis showed that BMI [odds ratio (OR) = 1.23, 95% confidence interval (95%CI) was 1.10-1.37, P = 0.000], pre-enrollment SCr (OR = 1.01, 95%CI was 1.00-1.02, P = 0.042), use of nephrotoxic drugs (OR = 2.84, 95%CI was 1.34-6.03, P = 0.007) and urinary TIMP2×IGFBP7 (OR = 2.19, 95%CI was 1.56-3.08, P = 0.000) was an independent risk factor for the occurrence of grade 2 or 3 AKI in critical patients. An AKI risk predictive model nomogram was constructed based on the independent risk factors of AKI. Bootstrap validation results showed that the model had good discrimination and calibration in internal validation. Receiver operator characteristic curve (ROC curve) analysis showed that the area under the ROC curve (AUC) of urinary TIMP2×IGFBP7 alone in predicting grade 2 or 3 AKI within 12 hours in critical patients was 0.74 (95%CI was 0.66-0.83), the optimal cut-off value was 1.40 (µg/L) 2/1 000 (sensitivity was 66.7%, specificity was 85.0%), and the predictive performance of the model incorporating urinary TIMP2×IGFBP7 was significantly better than that of the model without urinary TIMP2×IGFBP7 [AUC (95%CI): 0.85 (0.79-0.91) vs. 0.77 (0.70-0.84), P = 0.005], net reclassification index (NRI) was 0.29 (95%CI was 0.08-0.50, P = 0.008), integrated discrimination improvement (IDI) was 0.13 (95%CI was 0.07-0.19, P < 0.001). CONCLUSIONS: The AKI risk predictive model based on urinary TIMP2×IGFBP7 has high clinical value and is expected to be used to early predict the occurrence of AKI in critically ill patients.

Emerging non-antibody‒drug conjugates (non-ADCs) therapeutics of toxins for cancer treatment.

The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins. In recent years, toxins have been widely used as warheads for antibody‒drug conjugates (ADCs) due to their efficient killing activity against various cancer cells. Although ADCs confer certain targeting properties to the toxins, low drug loading capacity, possible immunogenicity, and other drawbacks also limit the potential application of ADCs. Recently, non-ADC delivery strategies for toxins have been extensively investigated. To further understand the application of toxins in anti-tumor, this paper provided an overview of prodrugs, nanodrug delivery systems, and biomimetic drug delivery systems. In addition, toxins and their combination strategies with other therapies were discussed. Finally, the prospect and challenge of toxins in cancer treatment were also summarized.

Electrochemical oxidative decarboxylative of α-oxocarboxylic acids towards the synthesis of quinazolines and quinazolinones.

A mild and environmentally electrochemical method for the synthesis of quinazolines and quinazolinones has been developed through anodic oxidation decarboxylative of α-oxocarboxylic acids. The present reaction was efficiently conducted by using simple and cheap NH4I as the N-source and electrolyte in an undivided cell. The desired products, quinazolines and quinazolinones, were isolated in high yield under chemical oxidant free conditions.

Efficient Photoelectrochemical Hydrogen Generation Based on Core Size Effect of Heterostructured Quantum Dots.

Colloidal quantum dots (QDs) are shown to be effective as light-harvesting sensitizers of metal oxide semiconductor (MOS) photoelectrodes for photoelectrochemical (PEC) hydrogen (H2) generation. The CdSe/CdS core/shell architecture is widely studied due to their tunable absorption range and band alignment via engineering the size of each composition, leading to efficient carrier separation/transfer with proper core/shell band types. However, until now the effect of core size on the PEC performance along with tailoring the core/shell band alignment is not well understood. Here, by regulating four types of CdSe/CdS core/shell QDs with different core sizes (diameter of 2.8, 3.1, 3.5, and 4.8 nm) while the thickness of CdS shell remains the same (thickness of 2.0 ± 0.1 nm), the Type II, Quasi-Type II, and Type I core/shell architecture are successfully formed. Among these, the optimized CdSe/CdS/TiO2 photoelectrode with core size of 3.5 nm can achieve the saturated photocurrent density (Jph) of 17.4 mA cm-2 under standard one sun irradiation. When such cores are further optimized by capping alloyed shells, the Jph can reach values of 22 mA cm2 which is among the best-performed electrodes based on colloidal QDs.

Polarization structured light 3D depth image sensor for scenes with reflective surfaces.

Highly reflective surfaces are notorious in the field of depth sensing and three-dimensional (3D) imaging because they can cause severe errors in perception of the depth. Despite recent progress in addressing this challenge, there are still no robust and error-free solutions. Here, we devise a polarization structured light 3D sensor for solving these problems, in which high-contrast-grating (HCG) vertical-cavity surface-emitting lasers (VCSELs) are used to exploit the polarization property. We demonstrate accurate depth measurements of the reflective surfaces and objects behind them in various imaging situations. In addition, the absolute error and effective measurement range are measured to prove the applicability for a wide range of 3D applications. Our work innovatively combines polarization and depth information, opening the way for fully understanding and applying polarization properties in the 3D domain.

Decarboxylative N-Formylation of Amines with Glyoxylic Acid Promoted by H2O2.

A novel method for the synthesis of formamides through the decarboxylative N-formylation of amines with glyoxylic acid has been developed. This transformation provides an efficient protocol for the synthesis of various formamides with moderate to excellent yields, and it can accommodate a wide range of functional groups under metal free and base free conditions. In addition, the large-scale experiments and high chemoselectivity have shown great potential application of this strategy.

HCC prediction models in chronic hepatitis B patients receiving entecavir or tenofovir: a systematic review and meta-analysis.

BACKGROUND: Our study aimed to compare the predictive performance of different hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B patients receiving entecavir or tenofovir, including discrimination, calibration, negative predictive value (NPV) in low-risk, and proportion of low-risk. METHODS: We conducted a systematic literature research in PubMed, EMbase, the Cochrane Library, and Web of Science before January 13, 2022. The predictive performance was assessed by area under receiver operating characteristic curve (AUROC), calibration index, negative predictive value, and the proportion in low-risk. Subgroup and meta-regression analyses of discrimination and calibration were conducted. Sensitivity analysis was conducted to validate the stability of the results. RESULTS: We identified ten prediction models in 23 studies. The pooled 3-, 5-, and 10-year AUROC varied from 0.72 to 0.84, 0.74 to 0.83, and 0.76 to 0.86, respectively. REAL-B, AASL-HCC, and HCC-RESCUE achieved the best discrimination. HCC-RESCUE, PAGE-B, and mPAGE-B overestimated HCC development, whereas mREACH-B, AASL-HCC, REAL-B, CAMD, CAGE-B, SAGE-B, and aMAP underestimated it. All models were able to identify people with a low risk of HCC accurately. HCC-RESCUE and aMAP recognized over half of the population as low-risk. Subgroup analysis and sensitivity analysis showed similar results. CONCLUSION: Considering the predictive performance of all four aspects, we suggest that HCC-RESCUE was the best model to utilize in clinical practice, especially in primary care and low-income areas. To confirm our findings, further validation studies with the above four components were required.

Diagnostic Value of the Combination of Ultrasonographic Optic Nerve Sheath Diameter and Width of Crural Cistern with Respect to the Intracranial Pressure in Patients Treated with Decompressive Craniotomy.

BACKGROUND: The monitoring of intracranial pressure (ICP) and detection of increased ICP are crucial because such increases may cause secondary brain injury and a poor prognosis. Although numerous ultrasound parameters, including optic nerve sheath diameter (ONSD), width of the crural cistern (WCC), and the flow velocities of the central retinal artery and middle cerebral artery, can be measured in patients after hemicraniectomy, researchers have yet to determine which of these is better for evaluating ICP. This study aimed to analyze the correlation between ICP and ultrasound parameters and investigate the best noninvasive estimator of ICP. METHODS: This observational study enrolled 50 patients with brain injury after hemicraniectomy from January 2021 to December 2021. All patients underwent invasive ICP monitoring with microsensor, transcranial, and ocular ultrasound postoperatively. We measured the ONSD including the dura mater (ONSDI), the ONSD excluding the dura mater, the optic nerve diameter (OND), the eyeball transverse diameter (ETD), the WCC, and the flow velocities in the central retinal artery and middle cerebral artery. Then, we calculated the ONSDI-OND (the difference between ONSDI and OND) and ONSDI/ETD (the ratio of ONSDI to ETD). Patients were divided into a normal ICP group (n = 35) and an increased ICP group (≥ 20 mm Hg, n = 15) according to the ICP measurements. Correlations were then assessed between the values of the ultrasound parameters and ICP. RESULTS: The ONSDI, ONSDI-OND, and ONSDI/ETD were positively associated with ICP (r = 0.455, 0.482, 0.423 and p = 0.001, < 0.001, 0.002, respectively), whereas the WCC was negatively associated with ICP (r = - 0.586, p < 0.001). The WCC showed the highest predictive power for increased ICP (area under the receiver operating characteristic curve [AUC] = 0.904), whereas the ONSDI-OND and ONSDI also presented with acceptable predictive power among the ONSD-related parameters (AUC = 0.831, 0.803, respectively). The cutoff values for increased ICP prediction for ONSDI, ONSDI-OND, and WCC were 6.29, 3.03, and 3.68 mm, respectively. The AUC of the combination of ONSDI-OND and WCC was 0.952 (95% confidence interval 0.896-1.0, p < 0.001). CONCLUSIONS: The ONSDI, ONSDI-OND, and WCC were correlated with ICP and had acceptable accuracy levels in estimating ICP in patients after hemicraniectomy. Furthermore, WCC showed a higher diagnostic value than ONSD-related parameters, and the combination of ONSDI-OND and WCC was a satisfactory predictor of increased ICP.

Age and Serum Creatinine Can Differentiate Wilson Disease Patients with Pseudonormal Ceruloplasmin.

Methods: We retrospectively screened individuals with serum Cp ≥ 140 mg/L from 1032 WD patients who were hospitalised for the first time. Logistic regression analyses were performed in a case-control study between the WD cohort and another liver disease cohort to explore the independent risk factors for WD diagnosis and establish a regression model to identify them. The follow-up medical records of the WD cohort were subjected to mixed-effects model analysis in a longitudinal study to discover factors associated with Cp normalisation. Results: Eighty-six WD patients and their 353 medical records and another 98 non-WD liver disease patients were included in the present study. Cp normalisation was significantly associated with the copper burden and liver function indexes, such as urinary copper, γ-glutamyltransferase, and albumin (p ≤ 0.001). Logistic regression analysis showed that age and serum creatinine (p ≤ 0.001) were independent risk factors associated with WD. The AUC value of the regression model in the total cohort was 0.926 (p ≤ 0.001). At a cutoff value of ≥0.617 and ≥-1, the positive and negative predictive values were both 90.8% for WD. Conclusion: Increased serum Cp in WD patients is related to excessive copper burden and hepatic injury, and common tests can effectively distinguish WD patients from other liver injury patients.

Screening and mutation analysis of phenylalanine hydroxylase deficiency in newborns from Jiangxi province.

Background: Phenylalanine hydroxylase deficiency (PAHD) is an autosomal recessive disorder of amino acid metabolism and caused by mutations in the phenylalanine hydroxylase (PAH) gene. Without timely and appropriate dietary management, the disturbance of amino acid metabolism may impair cognitive development and neurophysiological function. Newborn screening (NBS) can aid the early diagnosis of PAHD, which can give accurate therapy to PAHD patients in time. In China, the PAHD incidence and PAH mutation spectrum vary enormously across the provinces. A total of 5,541,627 newborns from Jiangxi province were screened by NBS between 1997 and 2021. Method: One seventy one newborns from Jiangxi province were diagnosed with PAHD. By Sanger sequencing and the multiplex ligation-dependent probe amplification (MLPA) analysis, mutation analysis was performed in 123 PAHD patients. Using an arbitrary values (AV)-based model, we compared the observed phenotype with the predicted phenotype based on the genotype. Results: In this study, we speculated the PAHD incidence of Jiangxi province was about 30.9 per 1,000,000 live births (171/5,541,627). We summarized the PAH mutation spectrum in Jiangxi province for the first time. Two novel variants (c.433G > C, c.706 + 2T > A) were found. The most prevalent variant was c.728G > A (14.1%). The overall prediction rate of the genotype-phenotype was 77.4%. Conclusion: This mutation spectrum is very meaningful to improve the diagnostic rate of PAHD and to increase the accuracy genetic counseling. This study offers data for the genotype-phenotype prediction suitable for Chinese population.

Changing incidence of hepatitis B and persistent infection risk in adults: a population-based follow-up study from 2011 in China.

BACKGROUND: This study aimed to estimate hepatitis B incidence and chronicity risk in rural adults in China under the background of eliminating viral hepatitis. METHODS: Hepatitis B surface antigen (HBsAg) screening was conducted every 2 years in demonstration areas since 2011. Individuals with baseline HBsAg-negative were included. Incidence was calculated as the number of HBsAg-positive cases divided by the total person-times. HBsAg-positive individuals were followed up to study the persistent infection (> 6 months), chronic infection (> 12 months), and recovery with hepatitis B surface antibody (anti-HBs). The chi-square test and cox proportional regression analysis were performed. RESULTS: There were 8,942 incident cases over 2,138,532 person-years, yielding an average incidence of 0.42 per 100 person-years. HBV incidence decreased rapidly in both genders and all age groups and then kept stable. Male gender, low population density, low gross domestic product per capita, and islanders were associated with higher incidence. Of the positive cases, 4,989 (55.8%) patients were followed up. The persistent infection, chronic infection, and recovery with anti-HBs rates were 32.3%, 31.0%, and 31.4%, respectively. Persistent or chronic infection was more common in younger adults and males, while seroconversion had no concern with gender or age. CONCLUSIONS: HBV incidence in adult rural residents was decreasing and stayed low. The chronicity rate was relatively high and protective antibodies were induced in only one third. The importance of population-based screening and vaccination for susceptible individuals should be addressed.

The effectiveness of pay-it-forward in addressing HPV vaccine delay and increasing uptake among 15-18-year-old adolescent girls compared to user-paid vaccination: a study protocol for a two-arm randomized controlled trial in China.

BACKGROUND: Human papillomavirus (HPV) vaccination could prevent cervical and other HPV-associated cancers attributable to vaccine-associated HPV types. However, HPV vaccination coverage among women aged 9-18 years old is low in China. Common barriers include poor financial affordability, minimal public engagement, and low confidence in domestically produced HPV vaccines. Pay-it-forward offers an individual a free or subsidized service then an opportunity to voluntarily donate and/or create a postcard message to support future people. This study aims to assess the effectiveness of pay-it-forward as compared to standard-of-care self-paid vaccination to improve HPV vaccine uptake among adolescent girls aged 15-18 years, who are left out in the current pilot free HPV vaccination task force in some parts of China. METHODS: This is a two-arm randomized controlled trial in Chengdu, China. Eligible adolescent girls (via caregivers) will be randomly selected and recruited through four community health centers (one in the most developed urban areas, one in higher middle-income and one in lower middle-income suburban areas, and one in the least developed rural areas) using the resident registration list. A total of 320 participants will be randomized into two study arms (user-paid versus pay-it-forward vaccination) in a 1:1 ratio. The intervention assignment will be blinded to recruiters and participants using envelop concealment until the research assistants open the envelop to determine which treatment to deliver to each individual. The primary outcome of the study will be HPV vaccine uptake by administrative data. Secondary outcomes include costs, vaccine hesitancy, and the completion rates of the 3-dose HPV vaccination series. DISCUSSION: This study will investigate an innovative pay-it-forward strategy's effectiveness and economic costs to improve HPV vaccination among 15-18-year-old adolescent girls. Study findings will have implications for increasing HPV vaccine uptake in places where HPV vaccines are provided for a fee. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR2200055542. Registered on 11 January 2022.

Inhibition of alanine-serine-cysteine transporter 2-mediated auto-enhanced photodynamic cancer therapy of co-nanoassembly between V-9302 and photosensitizer.

The efficiency of reactive oxygen species (ROS)-based photodynamic therapy (PDT) is far from satisfactory, because cancer cells can adapt to PDT by upregulating glutathione (GSH) levels. The GSH levels in tumor cells are determined based on glutamine availability via alanine-serine-cysteine transporter 2 (ASCT2)-mediated entry into cells. Herein, we develop co-assembled nanoparticles (PPa/V-9302 NPs) of the photosensitizer pyropheophorbide a (PPa) and V-9302 (a known inhibitor of ASCT2) in a 1:1 M ratio using a one-step precipitation method to auto-enhance photodynamic therapy. The computational simulations revealed that PPa and V-9302 could self-assemble through different driving forces, such as π-π stacking, hydrophobic interactions, and ionic bonds. Such PPa/V-9302 NPs could disrupt the intracellular redox homeostasis due to enhanced ROS production via PPa-induced PDT and reduced GSH synthesis via inhibition of the ASCT2-mediated glutamine flux by V-9302. The in vivo assays reveal that PPa/V-9302 NPs could increase the drug accumulation in tumor sites and suppress tumor growth in BALB/c mice bearing mouse breast carcinoma (4 T1) tumor. Our findings provide a new paradigm for the rational design of the PDT-based combinational cancer therapy.

Development of a UPLC-MS/MS method for the simultaneous determination of atorvastatin, 2-hydroxy atorvastatin, and naringenin in rat plasma and its application to pharmacokinetic interaction studies.

Recent studies have revealed that the combination therapy of atorvastatin (ATV) with naringenin (NG) can offer meaningful benefits in the treatment of hypercholesterolemia, while decreasing adverse side effects. To investigate whether there are pharmacokinetic interactions among ATV, its metabolite 2-hydroxy atorvastatin (2-ATV), and NG, in the current study, we developed and validated a simple, rapid, and specific UPLC-MS/MS method to simultaneously determine the concentrations of these analytes in the rat plasma. Sample preparation was performed using simple protein precipitation. Chromatographic analysis was carried out on an Acquity UPLC BEH C18 column (1.7 µm, 2.1 × 100 mm) using gradient elution mode, and these three analytes were detected using a Xevo® TQD triple quadrupole tandem mass spectrometer, in the positive ion electrospray ionization interface. The developed method showed good linearity over the following concentrations in rat plasma samples: 3-1200 ng/ml (r = 0.9965) for ATV, 1.5-600 ng/ml (r = 0.9934) for 2-ATV, and 3-1200 ng/ml (r = 0.9964) for NG. The assays were validated and satisfied the acceptance criteria recommended by U.S. Food and Drug Administration guidelines. Upon successful application of the method to a pharmacokinetic interaction study, the results indicated that NG significantly enhanced the bioavailability of ATV and 2-ATV.

Transcriptome analysis provides insights into light condition effect on paclitaxel biosynthesis in yew saplings.

BACKGROUND: Taxus is a rare gymnosperm plant that is the sole producer of the anticancer drug paclitaxel. The growth and development of Taxus is affected by environmental factors such as light. However, little is known about how light conditions affect growth and metabolic processes, especially paclitaxel biosynthesis. RESULTS: In this study, we applied three different light conditions to Taxus chinensis young saplings and investigated the physiological response and gene expression. Our observations showed that exposure to high light led to oxidative stress, caused photoinhibition, and damaged the photosynthetic systems in T. chinensis. The paclitaxel content in T. chinensis leaves was significantly decreased after the light intensity increased. Transcriptomic analysis revealed that numerous genes involved in paclitaxel biosynthesis and phenylpropanoid metabolic pathways were downregulated under high light. We also analyzed the expression of JA signaling genes, bHLH, MYB, AP2/ERF transcription factors, and the CYP450 families that are potentially related to paclitaxel biosynthesis. We found that several CYP450s, MYB and AP2/ERF genes were induced by high light. These genes may play an important role in tolerance to excessive light or heat stress in T. chinensis. CONCLUSIONS: Our study elucidates the molecular mechanism of the effects of light conditions on the growth and development of T. chinensis and paclitaxel biosynthesis, thus facilitating the artificial regeneration of Taxus and enhancing paclitaxel production.

Transcriptome profiling of transcription factors in Ganoderma lucidum in response to methyl jasmonate.

Ganoderma lucidum is a traditional Chinese medicine and its major active ingredients are ganoderma triterpenoids (GTs). To screen for transcription factors (TFs) that involved in the biosynthetic pathway of GTs in G. lucidum, the chemical composition in mycelia, primordium and fruiting body were analyzed, and the transcriptomes of mycelia induced by methyl jasmonate (MeJA) were analyzed. In addition, the expression level data of MeJA-responsive TFs in mycelia, primordia and fruiting body were downloaded from the database, and the correlation analysis was carried out between their expression profiles and the content of total triterpenoids. The results showed that a total of 89 components were identified, and the content of total triterpenoids was the highest in primordium, followed by fruiting body and mycelia. There were 103 differentially expressed TFs that response to MeJA-induction including 95 upregulated and 8 downregulated genes. These TFs were classified into 22 families including C2H2 (15), TFII-related (12), HTH (9), fungal (8), bZIP (6), HMG (5), DADS (2), etc. Correlation analysis showed that the expression level of GL23559 (MADS), GL26472 (HTH), and GL31187 (HMG) showed a positive correlation with the GTs content, respectively. While the expression level of GL25628 (fungal) and GL26980 (PHD) showed a negative correlation with the GTs content, respectively. Furthermore, the over expression of the Glmhr1 gene (GL25628) in Pichia pastoris GS115 indicated that it might be a negative regulator of GT biosynthesis through decreasing the production of lanosterol. This study provided useful information for a better understanding of the regulation of TFs involved in GT biosynthesis and fungal growth in G. lucidum.

Ultrasound-based artificial intelligence in gastroenterology and hepatology.

Artificial intelligence (AI), especially deep learning, is gaining extensive attention for its excellent performance in medical image analysis. It can automatically make a quantitative assessment of complex medical images and help doctors to make more accurate diagnoses. In recent years, AI based on ultrasound has been shown to be very helpful in diffuse liver diseases and focal liver lesions, such as analyzing the severity of nonalcoholic fatty liver and the stage of liver fibrosis, identifying benign and malignant liver lesions, predicting the microvascular invasion of hepatocellular carcinoma, curative transarterial chemoembolization effect, and prognoses after thermal ablation. Moreover, AI based on endoscopic ultrasonography has been applied in some gastrointestinal diseases, such as distinguishing gastric mesenchymal tumors, detection of pancreatic cancer and intraductal papillary mucinous neoplasms, and predicting the preoperative tumor deposits in rectal cancer. This review focused on the basic technical knowledge about AI and the clinical application of AI in ultrasound of liver and gastroenterology diseases. Lastly, we discuss the challenges and future perspectives of AI.