Artesunate promotes cervical cancer cell apoptosis by regulating Bcl2 family molecules and reducing the mitochondrial membrane potential.

Artesunate (ART), an antimalarial drug, has a broad spectrum of antitumour effects in cancer types such as esophageal and gastric cancer. However, evidence demonstrating the role of ART in cervical cancer cells is limited. In the present study, the inhibitory effect of ART on the growth of cervical cancer cells through the modulation of the cell cycle and apoptosis was investigated. The growth-inhibitory effect of ART on a cervical cancer cell line (SiHa) was detected using a Cell Counting Kit-8 assay after treatment with ART for 24 h, after which the half-maximal inhibitory concentration (IC50) was calculated. Using flow cytometry assays, apoptosis, the cell cycle, the levels of reactive oxygen species (ROS) and calcium (Ca2+) ions, as well as the mitochondrial membrane potential were evaluated in SiHa cells following treatment with ART for 24 and 48 h. The mRNA expression levels of Bcl2, Bcl-xl, (myeloid cell leukaemia 1) Mcl-1, Bcl2-like protein 11 (BIM), (Bcl2-related ovarian killer protein) Bok, Bax and (Bcl2 homologous antagonist/killer) Bak in SiHa cells were detected using reverse transcription-quantitative PCR. ART inhibited the growth of SiHa cells in a dose-dependent manner. The IC50 of ART in SiHa cells was 26.32 µg/ml. According to the IC50 value, 15, 30 and 100 µg/ml ART were selected for further experiments, and normal saline (0 µg/ml ART) was used as the control group. The results indicated that treatment with 15, 30 and 100 µg/ml ART for 24 and 48 h induced apoptosis, increased the levels of ROS, the levels of Ca2+ and the mRNA expression levels of BIM, Bok, Bax and Bak, but decreased the cell proliferation indices, the mitochondrial membrane potential and the mRNA expression levels of Bcl2, Bcl-xl and Mcl-1 in a dose- and time-dependent manner. In conclusion, ART inhibited the growth of SiHa cells and induced apoptosis via a mechanism associated with the regulation of Bcl2 family member expression, which was associated with the increase of the levels of ROS and Ca2+ and the reduction of the mitochondrial membrane potential.

Prognostic significance of ß2-microglobulin decline index in multiple myeloma.

Purpose: To assess the prognostic significance of ß2-microglobulin decline index (ß2M DI) in multiple myeloma (MM). Methods: 150 MM patients diagnosed with MM were enrolled in this study. Cox proportional hazards model was used to analyze the uni- and multivariate prognosis in training cohort (n=105). A new combined prognostic model containing ß2M DI was built up based on the data in training cohort. The validation group was used to verify the model. Results: ß2M DI showed significant correlation with prognosis in both uni- and multivariate analyses and had a good correlation with complete response (CR) rate and deep remission rate. The ROC and calibration curves in validation cohort (n=45) indicated a good predictive performance of the new model. Based on the median risk score of the training group, we classified patients into high- and low- risk groups. In both training and validation groups, patients in the low-risk group had longer overall survival (OS) time than that in the high-risk group (p<0.05). Conclusion: ß2M DI is a good predictive index for predicting treatment response and survival time in MM patients. The prognostic model added with ß2M DI showed a better correlation with OS.

Rapid Initiation of Peritoneal Dialysis by Automated Peritoneal Dialysis or Hemodialysis: A Randomized Clinical Trial.

Introduction: It is still controversial whether automated peritoneal dialysis (APD) or hemodialysis (HD) is a more favorable choice for the rapid initiation of peritoneal dialysis (PD). Methods: A pilot randomized prospective controlled trial was carried out in Shanghai Ruijin Hospital. Sixty-seven patients who chose long-term PD treatment and needed unplanned dialysis were enrolled and randomized into HD-CAPD group (33 cases) or APD-CAPD group (34 cases) based on the dialysis modality during the transition period (within 14 days from the day PD catheter was implanted). Continuous ambulatory PD started after the transition period. The primary outcome was the decline rates of residual glomerular filtration rate (GFR). Secondary outcomes included the rates of mechanical complications, the rates of infectious complications, and complications of end-stage renal disease. Results: We found residual GFR decline was faster in HD-CAPD group than in APD-CAPD group (0.06 mL/min/w vs. 0.03 mL/min/w, p < 0.01). The incidences of mechanical complications were similar in APD-CAPD group comparing with HD-CAPD group, including hernia (2.9% vs. 3.0%, p = 1.00), catheter malposition (0.02 episodes/patient-months vs. 0.02 episodes/patient-months, p = 0.70), leakage (5.9% vs. 6.1%, p = 1.00), and omental wrap (0 episode vs. 3 episodes, p = 0.368). Though the 1-year overall infection rates were similar (0.03 episodes/patient-months vs. 0.05 episodes/patient-months, p = 0.10), APD-CAPD group had lower rate of bacteremia compared to HD-CAPD group (0 episodes/patient-months vs. 0.02 episodes/patient-months, p < 0.01). Conclusions: Both APD and HD could be used for patients who need to start dialysis in an unplanned manner. APD may have the advantage in protecting residual renal functions among these patients.

Sensory attributes, chemical and microbiological properties of cigars aged with different media.

Introduction: Aging is an important process to improve the quality of cigar, but the effect of aging with media on cigar has not been reported.Therefore, this study aimed to prepare different aging media and clarify the influence of media on cigar quality. Methods: Effective media were first screened by sensory evaluation, then the effects of aging media on the chemical composition and microbial community of cigar were investigated. Results: The results showed that: 1) As aging media, coffee formula and cocoa formula could optimize the smoke and aroma characteristics of cigar, and 30 days was the appropriate period for cigar aging. 2) Aging with coffee or cocoa media could increase the content of amino acids, non-volatile organic acids, malic acid and aroma components. Particularly, the content of aroma components increased from 2.48 mg g-1 (W-30) to 3.21 mg g-1 (C-30) and 3.70 mg g-1 (K-30), respectively. 3) Aging with coffee can improve the diversity of bacteria and fungi on the cigar surface and change the succession rule of bacterial community. In contrast, aging with cocoa had no significant effect on microbial diversity of cigar. Discussion: In this study, the influence of aging media on cigar quality was analyzed multidimensionally for the first time, which provided a reference for the development of new aging media and technologies to improve cigar quality.

Skeletal muscle-secreted DLPC orchestrates systemic energy homeostasis by enhancing adipose browning.

MyoD is a skeletal muscle-specifically expressed transcription factor and plays a critical role in regulating myogenesis during muscle development and regeneration. However, whether myofibers-expressed MyoD exerts its metabolic function in regulating whole body energy homeostasis in vivo remains largely unknown. Here, we report that genetic deletion of Myod in male mice enhances the oxidative metabolism of muscle and, intriguingly, renders the male mice resistant to high fat diet-induced obesity. By performing lipidomic analysis in muscle-conditioned medium and serum, we identify 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC) as a muscle-released lipid that is responsible for MyoD-orchestrated body energy homeostasis in male Myod KO mice. Functionally, the administration of DLPC significantly ameliorates HFD-induced obesity in male mice. Mechanistically, DLPC is found to induce white adipose browning via lipid peroxidation-mediated p38 signaling in male mice. Collectively, our findings not only uncover a novel function of MyoD in controlling systemic energy homeostasis through the muscle-derived lipokine DLPC but also suggest that the DLPC might have clinical potential for treating obesity in humans.

Effects of a novel microbial fermentation medium produced by Tremella aurantialba SCT-F3 on cigar filler leaf.

Introduction: Adding a fermentation medium is an effective way to improve the quality of cigar tobacco leaves. Methods: A novel microbial fermentation medium produced by an edible medicinal fungus, Tremella aurantialba SCT-F3 (CGMCC No.23831) was used to improve the quality of cigar filler leaves (CFLs). Changes in sensory quality, chemical components, volatile flavor compounds (VFCs), and the structure and function of microbes were investigated during the fermentation process. Results: The sensory quality of CFLs supplemented with the T. aurantialba SCT-F3 fermentation medium significantly improved. Adding the fermentation medium increased the total alkaloid, reducing sugar, total sugar, and 12 VFCs significantly. A total of 31 microbial genera were significantly enriched, which increased the microbial community's richness and diversity. Microbial functions increased, including nucleotide biosynthesis, amino acid biosynthesis, fatty acid and lipid biosynthesis, nicotine degradation, and nicotinate degradation. During fermentation, the total alkaloid, reducing sugar, and total sugar content decreased. The richness and diversity of the microbial community decreased, whereas bacterial enzyme activity increased. At the end of fermentation, the sensory quality was excellent. The microbial structure gradually stabilized, and functional genes were low. The contents of the four Maillard reaction products and three nicotine degradation products increased significantly. 2-Ethyl-6-methylpyrazine, methylpyrazine, D,L-anatabine, ß-nicotyrine, nicotinic degradation products, and total nitrogen were significantly and positively correlated with sensory quality. Methylpyrazine, D,L-anatabine, and ß-nicotyrine were negatively correlated with Luteimonas, Mitochondria, Paracoccus, Stemphylium, and Stenotrophomonas. Conclusion: This research provides not only a new microbial fermentation medium that utilizes edible and medicinal fungi to improve the quality of fermented CFLs, but also new ideas for the development and application of other edible medicinal fungi to improve the quality of cigar tobacco leaves.

Effects of adding cocoa fermentation medium on cigar leaves in agricultural fermentation stage.

Background and Objective: With the development of the world economy and the integration of cultures, the Chinese cigar market has shown a significant upward trend. However, high-quality cigar leaves are mostly produced in Dominica, Cuba, Nicaragua and other places. In contrast, Chinese cigar leaves have problems such as insufficient aroma, which has become one of the main factors restricting the development of Chinese cigars. Adding medium to ferment is a traditional method in the cigar industry. At present, it mostly relies on manual experience, and lacks systematic and scientific research. At the same time, the addition of medium fermentation is mainly concentrated in the industrial fermentation process, and has not yet begun to be applied in the agricultural fermentation process. In this study, the medium was added to the agricultural fermentation process for the first time to explore the possibility of the application. The effects of adding cocoa medium to ferment on the chemical composition, sensory quality and surface microbial diversity of eggplant core cigar leaves were investigated.wrapper. Method: With Dexue 7' as the experimental material, the changes of main chemical components of wrapper fermented with water and cocoa medium were determined, and microbial community structure on the surface and relative abundance of cigar leaves at different turning periods were analyzed, and the functional genes were predicted. The results of the study were as follows: 1) The results of sensory evaluation showed that the addition of cocoa medium could highlight the aroma of bean, cocoa and coffee, improve the sweetness and fluency and the combustibility of cigar leaves. 2) The addition of cocoa medium increased the contents of proline and malic acid which were positively correlated with sensory quality, and decreased the contents of citric acid, linoleic acid, basic amino acids and aromatic amino acids which were negatively correlated with sensory quality. 3) The addition of cocoa medium increased the total amount of aroma components in cigar leaves, especially carotenoid degradation products, and changed the structural composition of some aroma substances in wrappercigar leaves. 4) The similarity of species composition between the water-added group and the cocoa-added group was higher, but the dominant microorganisms were more concentrated. Staphylococcus and Arthrobacter maintained a high relative abundance throughout the fermentation process, which may be the key microorganisms in the agricultural fermentation stage. 5) The addition of cocoa medium increased the expression abundance of related functional genes in cigar leaves, accelerated the fermentation process of cigar leaves, and bacteria played a major role in the fermentation process. Conclusion: Adding cocoa medium in the agricultural fermentation stage, the changes of bacterial community and dominant flora on the surface of cigar leaves are the main factors affecting their internal chemical components, and the addition of media has a positive effect on tobacco fermentation.

Comprehensive analysis of ferroptosis-related genes in immune infiltration and prognosis in multiple myeloma.

Background: One particular type of cellular death that is known as ferroptosis is caused by the excessive lipid peroxidation. It is a regulated form of cell death that can affect the response of the tumor cells. Currently, it is not known if the presence of this condition can affect the prognosis of patients with multiple myeloma (MM). Methods: In this study, we studied the expression differences and prognostic value of ferroptosis-related genes (FRGs) in MM, and established a ferroptosis risk scoring model. In order to improve the prediction accuracy and clinical applicability, a nomogram was also established. Through gene enrichment analysis, pathways closely related to high-risk groups were identified. We then explored the differences in risk stratification in drug sensitivity and immune patterns, and evaluated their value in prognostic prediction and treatment response. Lastly, we gathered MM cell lines and samples from patients to confirm the expression of marker FRGs using quantitative real-time PCR (qRT-PCR). Results: The ability to predict the survival of MM patients is a challenging issue. Through the use of a risk model derived from ferroptosis, we were able to develop a more accurate prediction of the disease's prognosis. They were then validated by a statistical analysis, which showed that the model is an independent factor in the prognosis of MM. Patients of high ferroptosis risk scores had a much worse chance of survival than those in the low-risk groups. The calibration and power of the nomogram were also strong. We noted that the link between the ferroptosis risk score and the clinical treatment was suggested by the FRG's significant correlation with the immune checkpoint genes and the medication sensitivity. We validated the predictive model using qRT-PCR. Conclusion: We demonstrated the association between FRGs and MM, and developed a new risk model for prognosis in MM patients. Our study sheds light on the potential clinical relevance of ferroptosis in MM and highlights its potential as a therapeutic target for patients with this disease.

Analysis of the structure and metabolic function of microbial community in cigar tobacco leaves in agricultural processing stage.

The agricultural fermentation processing of cigar tobacco leaves (CTLs), including air-curing and agricultural fermentation, carried out by tobacco farmers has rarely been studied. In this study, we have investigated the microbial community in the CTLs during air-curing and agricultural fermentation by 16S rRNA and ITS gene high-throughput sequencing. The results showed that the richness of microbial communities gradually increased with the development of agricultural fermentation, which means that not all microorganisms in CTLs come from the fields where tobacco grows, but gradually accumulate into CTLs during the fermentation process. Enterobacteriaceae, Chloroplast, and Alternaria were the dominant genera in the air-cured CTLs. Aquabacterium, unclassified Burkholderiaceae, Caulobacter, Brevundimonas, and Aspergillus were the dominant genera in the agriculturally fermented CTLs. Acinetobacter, Methylobacterium, Sampaiozyma, and Plectosphaerella first significantly increased, and then significantly decreased during agricultural processing. The changes in microbial communities are mainly related to their different functions during fermentation. This means that when the fermentation effect of the original microbial community in cigar tobacco leaves is not ideal, we can optimize or design the microbial community based on the fermentation function that the microbial community needs to achieve. These results may help adjust and optimize the agricultural fermentation process of CTLs, and help develop the quality of CTLs and increase the income of tobacco farmers.

FNBP1 Facilitates Cervical Cancer Cell Survival by the Constitutive Activation of FAK/PI3K/AKT/mTOR Signaling.

Cervical cancer is the most prevalent gynecological tumor among women worldwide. Although the incidence and mortality of cervical cancer have been declining thanks to the wide-scale implementation of cytological screening, it remains a major challenge in clinical treatment. High viability is one of the leading causes of the chemotherapeutic resistance in cervical cancers. Formin-binding protein 1 (FNBP1) could stimulate F-actin polymerization beneath the curved plasma membrane in the cell migration and endocytosis, which had previously been well defined. Here, FNBP1 was also demonstrated to play a crucial role in cervical cancer cell survival, and the knockdown of which could result in the attenuation of FAK/PI3K/AKT signaling followed by significant apoptotic accumulation and proliferative inhibition. In addition, the epidermal growth factor (hrEGF) abrogated all the biological effects mediated by the silencing of FNBP1 except for the cell adhesion decrease. These findings indicated that FNBP1 plays a key role in maintaining the activity of focal adhesion kinase (FAK) by promoting cell adhesion. The activated FAK positively regulated downstream PI3K/AKT/mTOR signaling, which is responsible for cell survival. Promisingly, FNBP1 might be a potential target against cervical cancer in combination therapy.

A novel glycolysis-related gene signature for predicting the prognosis of multiple myeloma.

Background: Metabolic reprogramming is an important hallmark of cancer. Glycolysis provides the conditions on which multiple myeloma (MM) thrives. Due to MM's great heterogeneity and incurability, risk assessment and treatment choices are still difficult. Method: We constructed a glycolysis-related prognostic model by Least absolute shrinkage and selection operator (LASSO) Cox regression analysis. It was validated in two independent external cohorts, cell lines, and our clinical specimens. The model was also explored for its biological properties, immune microenvironment, and therapeutic response including immunotherapy. Finally, multiple metrics were combined to construct a nomogram to assist in personalized prediction of survival outcomes. Results: A wide range of variants and heterogeneous expression profiles of glycolysis-related genes were observed in MM. The prognostic model behaved well in differentiating between populations with various prognoses and proved to be an independent prognostic factor. This prognostic signature closely coordinated with multiple malignant features such as high-risk clinical features, immune dysfunction, stem cell-like features, cancer-related pathways, which was associated with the survival outcomes of MM. In terms of treatment, the high-risk group showed resistance to conventional drugs such as bortezomib, doxorubicin and immunotherapy. The joint scores generated by the nomogram showed higher clinical benefit than other clinical indicators. The in vitro experiments with cell lines and clinical subjects further provided convincing evidence for our study. Conclusion: We developed and validated the utility of the MM glycolysis-related prognostic model, which provides a new direction for prognosis assessment, treatment options for MM patients.

Identification and validation of a novel cuproptosis-related gene signature in multiple myeloma.

Background: Cuproptosis is a newly identified unique copper-triggered modality of mitochondrial cell death, distinct from known death mechanisms such as necroptosis, pyroptosis, and ferroptosis. Multiple myeloma (MM) is a hematologic neoplasm characterized by the malignant proliferation of plasma cells. In the development of MM, almost all patients undergo a relatively benign course from monoclonal gammopathy of undetermined significance (MGUS) to smoldering myeloma (SMM), which further progresses to active myeloma. However, the prognostic value of cuproptosis in MM remains unknown. Method: In this study, we systematically investigated the genetic variants, expression patterns, and prognostic value of cuproptosis-related genes (CRGs) in MM. CRG scores derived from the prognostic model were used to perform the risk stratification of MM patients. We then explored their differences in clinical characteristics and immune patterns and assessed their value in prognosis prediction and treatment response. Nomograms were also developed to improve predictive accuracy and clinical applicability. Finally, we collected MM cell lines and patient samples to validate marker gene expression by quantitative real-time PCR (qRT-PCR). Results: The evolution from MGUS and SMM to MM was also accompanied by differences in the CRG expression profile. Then, a well-performing cuproptosis-related risk model was developed to predict prognosis in MM and was validated in two external cohorts. The high-risk group exhibited higher clinical risk indicators. Cox regression analyses showed that the model was an independent prognostic predictor in MM. Patients in the high-risk group had significantly lower survival rates than those in the low-risk group (p < 0.001). Meanwhile, CRG scores were significantly correlated with immune infiltration, stemness index and immunotherapy sensitivity. We further revealed the close association between CRG scores and mitochondrial metabolism. Subsequently, the prediction nomogram showed good predictive power and calibration. Finally, the prognostic CRGs were further validated by qRT-PCR in vitro. Conclusion: CRGs were closely related to the immune pattern and self-renewal biology of cancer cells in MM. This prognostic model provided a new perspective for the risk stratification and treatment response prediction of MM patients.

Advances in self-assembled Au-DNA nanomachines.

Au-DNA self-assembled nanomachines can perform intelligent tasks such as sensing biomarkers and delivery of drug molecules through rational customization and programming. By virtue of their efficient signal amplification and flexible scalability, Au-DNA nanomachines have developed into one of the most promising nanodevices. In this review, we summarize the latest progress in Au-DNA self-assembled nanomachines for biosensing applications. First, the functional modules for building Au-DNA nanomachines are introduced. Subsequently, we summarize the biosensing applications of Au-DNA nanomachines with electrochemical or fluorescent signals as the output, respectively. Finally, we discuss the challenges and potential opportunities for Au-DNA nanomachines in biomedical applications.

High throughput screening of key functional strains based on improving tobacco quality and mixed fermentation.

Background: Tobacco alcoholization is an important step in increasing the quality of tobacco leaf, which may convert a portion of low-grade tobacco leaves into useable product, however this may take to 2-3 years. The addition of exogenous microorganisms to tobacco leaves and treating them by biological fermentation can shorten the maturation time of tobacco leaves, and improve the quality and applicability of low-grade tobacco leaves Methods: Several strains were screened from low-grade tobacco by flow cytometry, including the bacteria Bacillus amyloliticus, with starch degradation ability and Bacillus kochii, with protein degradation ability, and the fungus Filobasidium magnum with lipid oxidase ability, and were inoculated onto tobacco leaves, both individually and in combination, for solid-state fermentation Results: The greatest improvement in tobacco quality was observed when strains 4# and 3# were applied at a ratio of 3:1. The Maillard reaction products, such as 2-amyl furan, 1-(2-furanmethyl) -1 h-pyrrole, furfural and 2, 5-dimethylpyrazine, were significantly increased, by up to more than 2 times. When strains F7# and 3# were mixed at a ratio of 3:1, the improvement of sensory evaluation index was better than that of pure cultures. The increase of 3-(3, 4-dihydro-2h-pyrro-5-yl) pyridine, ß -damasone and benzyl alcohol was more than 1 times. The increase of 2-amyl-furan was particularly significant, up to 20 times Conclusion: The functional strains screened from tobacco leaves were utilized for the biological fermentation of tobacco leaves, resulting in the reduction of irritation and an improvement in quality of final product, showing a good potential for application.

Intrinsic Image Transfer for Illumination Manipulation.

This article presents a novel intrinsic image transfer (IIT) algorithm for image illumination manipulation, which creates a local image translation between two illumination surfaces. This model is built on an optimization-based framework composed of illumination, reflectance and content photo-realistic losses, respectively. Each loss is first defined on the corresponding sub-layers factorized by an intrinsic image decomposition and then reduced under the well-known spatial-varying illumination illumination-invariant reflectance prior knowledge. We illustrate that all losses, with the aid of an "exemplar" image, can be directly defined on images without the necessity of taking an intrinsic image decomposition, thereby giving a closed-form solution to image illumination manipulation. We also demonstrate its versatility and benefits to several illumination-related tasks: illumination compensation, image enhancement and tone mapping, and high dynamic range (HDR) image compression, and show their high-quality results on natural image datasets.

A Telomerase-Assisted Strategy for Regeneration of DNA Nanomachines in Living Cells.

DNA nanomachines have been engineered into diverse personalized devices for diagnostic imaging of biomarkers; however, the regeneration of DNA nanomachines in living cells remains challenging. Here, we report an ingenious DNA nanomachine that can implement telomerase (TE)-activated regeneration in living cells. Upon apurinic/apyrimidinic endonuclease 1 (APE1)-responsive initiation of the nanomachine, the walker of the nanomachine moves along tracks regenerated by TE, generating multiply amplified signals through which APE1 can be imaged in situ. Additionally, augmentation of the signal due to the regeneration of the nanomachines could reveal differential expression of TE in different cell lines. To the best of our knowledge, this is the first proof-of-concept demonstration of the use of biomarkers to assist in the regeneration of nanomachines in living cells. This study offers a new paradigm for the development of more applicable and efficient DNA nanomachines.

Hyperthermia-sensitive Liposomes Containing Brucea Javanica Oil for Synergistic Photothermal-/Chemo-Therapy in Breast Cancer Treatment.

INTRODUCTION: High mortality and limited therapeutic efficacy of clinical treatment make breast cancer a stubborn disease in women. The hypovascular issue is the main challenge needed to be overcome in breast cancer treatment. METHODS: For this purpose, hyperthermia-sensitive liposomes containing indocyanine green (ICG) and brucea javanica oil (BJO) (LP(BJO/ICG)) were constructed for near-infrared (NIR) laser-induced photothermal- /chemo-antitumor therapy. ICG, an FDA-approved photothermal agent, was employed in this study to perform photothermal therapy (PTT) effect as well as relieve hypovascular conditions in breast cancer tissue. RESULTS: BJO triggered release from the hyperthermia-sensitive LP (BJO/ICG) due to disassembly of liposomes under the PTT effect caused by ICG under NIR laser irradiation. It was found that mice in LP (BJO/ICG) group showed the slowest tumor growth under NIR laser irradiation, illustrating the strongest antitumor effect among all groups. CONCLUSION: This responsive-release drug delivery platform can be a promising candidate for the treatment of breast cancer.

Pneumocystis jirovecii pneumonia in non-Hodgkin's lymphoma after rituximab-based chemotherapy: a case series.

Background: The incidence of Pneumocystis jirovecii pneumonia (PCP) has been increasing in patients with hematologic malignancies due to the use of glucocorticoid therapy and immunosuppressive medication. The reports of PCP in non-Hodgkin's lymphoma (NHL) after rituximab-based chemotherapy are still rare. We reported a case series of PCP in NHL to show the clinical features and prognosis in those patients. Methods: We conducted a retrospective review of 15 NHL patients who developed PCP after rituximab-based chemotherapy during June 30, 2014 to June 1, 2020. We analyzed the laboratory and radiographic findings for those patients through descriptive statistics analysis. Results: The study revealed that PCP in NHL patients was complicated by chemotherapy after about 4 courses (range, 2 to 6 courses). Most patients had a standard lymphocyte count before treatment, and 14 of 15 patients (93.3%) had lymphopenia at the time of diagnosis of PCP. In addition to typical symptoms such as fever and dyspnea at the diagnosis of PCP, most patients had abnormal laboratory indexes such as marked elevations of C-reactive protein (CRP) and lactic dehydrogenase (LDH) both before and at the time of diagnosis. The (1,3)-ß-D-glucan test was also revealed as a sensitive index for PCP. Bilateral ground-glass opacity was detected in 14 cases through computed tomography (CT) scans. Positive results of microbiological testing were observed in 7 cases; sputum culture was positive in 3 and next-generation sequencing (NGS) was positive in 3 of these 7 patients, and the other case was positive in both sputum culture and NGS. Patients received high-dose trimethoprim/sulfamethoxazole (TMP/SMZ), caspofungin, and steroids as the treatment for PCP. Ventilatory support was required by 3 patients, so they were admitted to the intensive care unit (ICU), and 1 patient died from PCP. Conclusions: Dynamic monitoring of CRP, LDH, and (1,3)-ß-D-glucan test during the treatment of NHL may have a predictive value for the diagnosis of PCP. Additionally, we should use NGS as a rapid and sensitive method for the early diagnosis of PCP. When patients are classified as 'probable PCP', early and effective treatment has obvious significance to improve the prognosis.

Hydrochlorothiazide/Losartan Potassium Tablet Prepared by Direct Compression.

Hydrochlorothiazide (HCTZ)/losartan potassium (LOS-K) was used as a model drug to prepare compound tablets through the investigation of the compression and mechanical properties of mixed powders to determine the formulation and preparation factors, followed by D-optimal mixture experimental design to optimize the final parameters. The type and amount of lactose monohydrate (SuperTab®14SD, 19.53−26.91%), microcrystalline cellulose (MCC PH102, 32.86−43.31%), pre-gelatinized starch (Starch-1500, 10.96−15.91%), and magnesium stearate (0.7%) were determined according to the compressive work, stress relaxation curves, and Py value. Then, the compression mechanism of the mixed powder was investigated by the Kawakita equation, Shapiro equation, and Heckel analysis, and the mixed powder was classified as a Class-II powder. The compaction pressure (150−300 MPa) and tableting speed (1200−2400 Tab/h) were recommended. A D-optimal mixture experimental design was utilized to select the optimal formulation (No 1, 26.027% lactose monohydrate, 32.811% MCC PH102, and 15.462% pregelatinized starch) according to the drug dissolution rate, using Hyzaar® tablets as a control. Following oral administration in beagle dogs, there were no significant differences in bioavailability between the No. 1 tablet and the Hyzaar® tablet in HCTZ, losartan carboxylic acid (E-3174), and LOS-K (F < F0.05). Thus, formulation and preparation factors were determined according to the combination of the compression and mechanical properties of the mixed powder and quality of tablets, which was demonstrated to be a feasible method in direct powder compression.