Assessment of anti-PD-(L)1 for patients with coexisting malignant tumor and tuberculosis classified by active, latent, and obsolete stage.

BACKGROUND: It is not a rare clinical scenario to have patients presenting with coexisting malignant tumor and tuberculosis. Whether it is feasible to conduct programmed death-(ligand) 1 [PD-(L)1] inhibitors to these patients, especially those with active tuberculosis treated with concurrent anti-tuberculosis, is still unknown. METHODS: This study enrolled patients with coexisting malignancy and tuberculosis and treated with anti-PD-(L)1 from Jan 2018 to July 2021 in 2 institutions. The progression-free survival (PFS), objective response rate (ORR), and safety of anti-PD-(L)1 therapy, as well as response to anti-tuberculosis treatment, were evaluated. RESULTS: A total of 98 patients were screened from this cohort study, with 45 (45.9%), 21 (21.4%), and 32 (32.7%) patients diagnosed with active, latent, and obsolete tuberculosis, respectively. The overall ORR was 36.0% for anti-PD-(L)1 therapy, with 34.2%, 35.5%, and 41.2% for each subgroup. Median PFS was 8.0 vs 6.0 vs 6.0 months (P=0.685) for each subgroup at the time of this analysis. For patients with active tuberculosis treated with concurrent anti-tuberculosis, median duration of anti-tuberculosis therapy was 10.0 (95% CI, 8.01-11.99) months. There were 83.3% (20/24) and 93.3% (42/45) patients showing sputum conversion and radiographic response, respectively, after anti-tuberculosis therapy, and two patients experienced tuberculosis relapse. Notably, none of the patients in latent and only one patient in obsolete subgroups showed tuberculosis induction or relapse after anti-PD-(L)1 therapy. Treatment-related adverse events (TRAEs) occurred in 33 patients (73.3%) when treated with concurrent anti-PD-(L)1 and anti-tuberculosis. Grade 3 or higher TRAEs were hematotoxicity (n = 5, 11.1%), and one patient suffered grade 3 pneumonitis leading to the discontinuation of immunotherapy. CONCLUSIONS: This study demonstrated that patients with coexisting malignant tumor and tuberculosis benefited equally from anti-PD-(L)1 therapy, and anti-tuberculosis response was unimpaired for those with active tuberculosis. Notably, the combination of anti-PD-(L)1 and anti-tuberculosis therapy was well-tolerated without significant unexpected toxic effects.

A sensitive photothermometric biosensor based on redox reaction-controlled nanoprobe conversion from Prussian blue to Prussian white.

As a new low-cost photothermal nanoprobe, Prussian blue nanoparticles (PB NPs) have been demonstrated to have more potential in photothermometric-based point-of-care testing (POCT) application. However, most of the existing PB NP-based photothermometric sensors were constructed mainly relying on in situ generation of PB NPs or their combination with antigens and antibodies, therefore usually suffering from the inherent defects like complicated preparation and cumbersome surface process as well as high-cost modification. To break this limitation of PB NP-based photothermometric POCT, we proposed an ingenious redox reaction-controlled nanoprobe conversion strategy and successfully applied to photothermometric detection of ascorbate oxidase (AAO). In this design, the heat of PB NP photothermal system under 808-nm laser irradiation dramatically decreased with the addition of AA, due to a unique AA-induced Prussian blue to Prussian white (PB-to-PW) conversion. Upon AAO addition, the heat of reaction system increased because of the enzymatic catalytic reaction between AAO and AA, which led to a significant reduction of AA and resultantly inhibited PB-to-PW conversion. Such target-mediated nanoprobe conversion resulted in an obvious temperature change that could be easily detected by a common thermometer and exhibited good linear ranges from 0.25 to 14 mU/mL with a detection limit as low as 0.21 mU/mL for POCT analysis of AAO. This facile, convenient, and portable photothermometric sensing platform provides an innovative route for the design of PB NP nanoprobe-based photothermometric detection methods. A sensitive photothermometric AAO sensor based on a redox reaction-controlled nanoprobe conversion strategy from Prussian blue to Prussian white.

Inhibition of N-acetylglucosaminyltransferase V enhances sensitivity of radiotherapy in human prostate cancer.

The purpose of this study was to investigate the relationship between N-acetylglucosaminyltransferase V (GnT-V) and radiation sensitivity of prostate cancer (PCa) cells both in vitro and in vivo. Firstly, the GnT-V expression was studied in 84 cases of PCa tissues, in which higher level of GnT-V was detected more frequently in the advanced tumors. Secondly, the GnT-V stably suppressed cell lines PCa/1079 (Lncap/1079 and PC3/1079) were constructed from PCa cell lines (Lncap and PC3) in vitro. Attenuation of GnT-V inhibited cell proliferation, migration and increased apoptosis, which resulted in enhanced radiation sensitivity of PCa cells. The underlying mechanism may be relevant to the increasing ratio of Bax/Bcl-2, the blocking transcription of NF-κB and the reduction of cell cycle G2-M arrest. Finally, in in vivo study, compared with control groups, the irradiated PCa xenograft nude mice of PCa/1079 indicated to reduce tumor-growth rate and enhance survival time. Summary, our studies showed that inhibition of GnT-V probably improved PCa cells' radiation sensitivity.

Engineered exosomes: a potential therapeutic strategy for septic cardiomyopathy.

Septic cardiomyopathy, a life-threatening complication of sepsis, can cause acute heart failure and carry a high mortality risk. Current treatments have limitations. Fortunately, engineered exosomes, created through bioengineering technology, may represent a potential new treatment method. These exosomes can both diagnose and treat septic cardiomyopathy, playing a crucial role in its development and progression. This article examines the strategies for using engineered exosomes to protect cardiac function and treat septic cardiomyopathy. It covers three innovative aspects: exosome surface modification technology, the use of exosomes as a multifunctional drug delivery platform, and plant exosome-like nanoparticle carriers. The article highlights the ability of exosomes to deliver small molecules, proteins, and drugs, summarizing several RNA molecules, proteins, and drugs beneficial for treating septic cardiomyopathy. Although engineered exosomes are a promising biotherapeutic carrier, they face challenges in clinical application, such as understanding the interaction mechanism with host cells, distribution within the body, metabolism, and long-term safety. Further research is essential, but engineered exosomes hold promise as an effective treatment for septic cardiomyopathy.

Intrathecal ultra-low dose naloxone enhances the antihyperalgesic effects of morphine and attenuates tumor necrosis factor-α and tumor necrosis factor-α receptor 1 expression in the dorsal horn of rats with partial sciatic nerve transection.

BACKGROUND: Glutamate homeostasis and microglia activation play an important role in the development and maintenance of neuropathic pain. We designed this investigation to examine whether ultra-low dose naloxone administered alone or in combination with morphine could alter the concentration of the excitatory amino acids (EAAs) glutamate and aspartate, as well as the expression of tumor necrosis factor-α (TNF-α) and its receptors (TNFR1 and TNFR2) in the spinal cord dorsal horn of rats with partial sciatic nerve transection (PST). METHODS: Male Wistar rats underwent intrathecal catheter implantation for drug delivery and were divided in 7 groups: sham-operated + saline (sham), PST + saline (S), PST + 15 ng naloxone (n), PST + 15 µg naloxone (N), PST + 10 µg morphine (M), PST + 15 ng naloxone + 10 µg morphine (Mn), PST + 15 µg naloxone + 10 µg morphine (MN). Thermal withdrawal latency and mechanical withdrawal threshold, TNF-α and TNFR expression in the spinal cord and dorsal root ganglia, and EAAs glutamate and aspartate concentration in cerebrospinal fluid dialysates were measured. RESULTS: Ten days after PST, rats developed hyperalgesia (P < 0.0001) and allodynia (P < 0.0001), and increased TNF-α (P < 0.0001) and TNFR1 expression (P = 0.0009) were measured in the ipsilateral spinal cord dorsal horn. The antihyperalgesic and antiallodynic effects of morphine (10 µg) were abolished by high-dose naloxone (15 µg; P = 0.0031) but enhanced by ultra-low dose naloxone (15 ng; P = 0.0015), and this was associated with a reduction of TNF-α (P < 0.0001) and TNFR1 (P = 0.0009) expression in the spinal cord dorsal horn and EAAs concentration (glutamate: P = 0.0001; aspartate: P = 0.004) in cerebrospinal fluid dialysate. Analysis of variance (ANOVA) or Student t test with Bonferroni correction were used for statistical analysis. CONCLUSIONS: Ultra-low dose naloxone enhances the antihyperalgesia and antiallodynia effects of morphine in PST rats, possibly by reducing TNF-α and TNFR1 expression, and EAAs concentrations in the spinal dorsal horn. Ultra-low dose naloxone may be a useful adjuvant for increasing the analgesic effect of morphine in neuropathic pain conditions.

Ten-year phantom limb pain with only four sessions of Fu's subcutaneous needling: A case report and systematic review.

Phantom limb pain (PLP) is a distressing consequence commonly encountered by individuals who have undergone amputations. The efficacy of treatment options for PLP is limited. In this study, we present a case of a 64-year-old male who suffered from PLP for a duration of 10 years following an above-the-knee amputation. Despite unsuccessful attempts with painkillers and neurotrophic drugs over the course of a decade, the patient sought relief through Fu's Subcutaneous Needling (FSN), an innovative acupuncture therapy that specifically targets the subcutaneous tissue for pain management. Remarkably, the patient experienced a significant reduction in PLP and subsequently decreased his reliance on medication, as well as experiencing improved sleep after undergoing one session of FSN per day for four consecutive days. A follow-up conducted three years later demonstrated positive treatment outcomes. FSN demonstrated a significant influence on PLP, resulting in reduced analgesic requirements and enhanced quality of life. Therefore, FSN may be recommended as an additional treatment option for PLP. In order to gain a comprehensive understanding of the effects of acupuncture on PLP, a systematic review of relevant literature was conducted in PubMed, Embase, Cochrane Library and Web of Science in recent 20 years (from January 1, 2003 to October 16, 2023), using different combinations of the following terms: (phantom acrodynia), (residual limb pain), (phantom limb pain), (acupuncture), (electroacupuncture), (auriculoacupuncture), and (needling). 9 articles with 18 cases including one randomized controlled trial (n = 8) were obtained. This review provided additional evidence supporting the efficacy and safety of needling therapies for PLP. This systematic review offers additional evidence supporting the effectiveness and safety of needling therapies for PLP. However, there were no precedent reports using FSN treatment for PLP. Hence, this case may provide some implications for clinicians in practice.

Subcutaneous stretching enlarges adjacent vertebral artery instantly in patients with cervicogenic dizziness: Two case reports.

RATIONALE: Fu's subcutaneous needling (FSN) is effective for cervicogenic dizziness (CGD), which is often a result of vascular problems. Here, we attribute the positive treatment effect of FSN for CGD to improvements in vascular problems. PATIENT CONCERN: Two patients were experiencing low quality of life due to reproducible dizziness. DIAGNOSIS: Two patients with cervical spine disorder, presented with neck pain and reproducible dizziness. Other causes of dizziness were excluded. INTERVENTIONS: Case 1 received 1 session of FSN treatment, while case 2 received 3 sessions of FSN treatment in a month. OUTCOMES: The dizziness and neck pain experienced by both patients instantly improved significantly after FSN treatment, and the luminal diameter of the vertebral artery (VA) measured by carotid and VA ultrasound enlarged simultaneously up to 1.29-fold and 1.09-fold for both cases. According to the Hagen-Poiseuille equation, the blood flow volume increased 2.77-fold and 1.43-fold, respectively. Case 2 recovered from CGD with 1.19-fold VA luminal diameter increment and about 2.01-fold increase of blood flow volume in a month. LESSONS: Subcutaneous stretching provides a safe, convenient and immediate solution to CGD, and supports the diagnosis and treatment of CGD under carotid and VA ultrasound. This study suggests that stretching subcutaneously can influence adjacent VA, which may also help improve some cerebrovascular diseases.

Treatment of postsurgical gastroparesis syndrome with Fu's subcutaneous needling: A case report.

Postsurgical gastroparesis syndrome is a syndrome of significantly delayed gastric emptying in the absence of mechanical obstruction after surgery. We presented a case of 69-year-old male patient who suffered from progressive nausea, vomiting and stomach fullness, with a bloating abdomen ten days after laparoscopic radical gastrectomy for gastric cancer. Conventional treatments such as gastrointestinal decompression, gastric acid suppression therapy and intravenous nutritional support were administrated, but there were no obvious improvements in nausea, vomiting, abdominal distension of this patient. Fu's subcutaneous needling was performed once a day for three days, for a total of three treatments. After three days of Fu's subcutaneous needling intervention, he was free of symptoms of nausea, vomiting and stomach fullness. His gastric drainage volume reduced from 1000 ml per day to 10 ml per day. Upper gastrointestinal angiography showed normal peristalsis of remnant stomach. In this case report, Fu's subcutaneous needling showed a potential role of gastrointestinal motility enhancement and gastric drainage volume decrement, which provided a safe and convenient method in palliative care of postsurgical gastroparesis syndrome.

Double-template-regulated biomimetic construction and tribological properties of superdispersed calcium borate@polydopamine/cellulose acetate-laurate nanocomposite.

Herein, a novel superdispersed calcium borate@polydopamine/cellulose acetate-laurate nanocomposite (CTAB-CB@PDA/CAL) is successfully synthesized by a double-template-regulated biomimetic mineralization strategy using PDA/CAL as a hard template and cetyltrimethylammonium bromide (CTAB) as a soft template and surface hydrophobic modifier. The results show that CB can grow uniformly on the CAL surface, and CTAB can improve the hydrophobicity of CTAB-CB@PDA/CAL due to the synergistic effect of the double templates, which contributes to the enhanced dispersibility and long-term dispersion stability of CTAB-CB@PDA/CAL in poly-alpha-olefin (PAO) base oil. Furthermore, CB can rapidly enter the friction interface due to the long substituents of CTAB and CAL, so CTAB-CB@PDA/CAL used as a lubricant additive in PAO base oil exhibits superior tribological performance compared to CB, CB/CAL, and CB@PDA/CAL.

Synergistic Effect of Hyperactive Antifreeze Protein on Inhibition of Gas-Hydrate Growth by Hydrophobic and Hydrophilic Groups.

Antifreeze proteins (AFPs) are biodegradable inhibitors that effectively prevent the formation of natural gas hydrates that block pipelines. In this study, molecular dynamics simulations were employed to establish a kinetic model of the hyperactive insect antifreeze protein (Tenebrio molitor, TmAFP) and its mutants to inhibit the growth of sI natural methane hydrate. Simulations revealed that the hydrophobic and hydrophilic groups of threonine (Thr) residues at hydrate-binding sites played a synergistic role in binding hydrates. The hydrophobic groups anchored TmAFP to the hydrate surface through residues Thr39-Thr65 by migrating pendant hydrophobic methyl groups to the hydrate semicages. The hydrophilic groups stabilized TmAFP by hydrogen bonding with water molecules and integrating them into a quasi-hydrate structure, which more effectively inhibited hydrate growth. The results suggest that the hydrate growth inhibition is attributed to both the shape complementarity and the flexibility of binding residues. The synergy between hydrophobic and hydrophilic groups provides guidance for the design of more effective hydrate inhibitors.

Adjacent Fu's subcutaneous needling as an adjunctive healing strategy for diabetic foot ulcers: Two case reports.

RATIONALE: Diabetic foot ulcers (DFUs) present with different grades of ischemia and infection and are associated with high mortality and disability rates with little effective treatment. We used Fu Subcutaneous Needling (FSN) to treat 2 cases with DFUs and achieved satisfactory results. PATIENT CONCERNS: Two cases of DFUs showed poor recovery after conventional wound care treatment, and case 2 was confronted with the risk of amputation. DIAGNOSIS: Two patients with history of diabetes were diagnosed with DFUs, presenting with lower leg and foot ulcers. INTERVENTIONS: Case 1 received 6 sessions of FSN treatment in 8 days, and case 2 received 10 sessions of FSN treatment in 14 days. OUTCOMES: Case 1 completely healed from a 1 × 0.5-cm blister and a 0.5 × 0.5-cm ulcer of the right lower leg 14 days after the first FSN treatment. The ulcer area of the left foot in case 2 decreased from 6 × 7 cm to 4 × 3.5 × 0.2 cm. Three months of follow-up revealed full wound closure. LESSONS: FSN is effective for healing with DFUs, and it may be used as an adjunctive healing strategy for DFUs patients when conventional treatments such as infection, glycemic control, and local ulcer care are not available.

Positive correlation between VCA-IgM and Th1/Th2 immunocytokines in children with infectious mononucleosis.

OBJECTIVE: To analyze the correlation between immunoglobulin M (IgM) against viral capsid antigen (VCA) of Epstein-Barr virus (EBV) and T helper 1 and 2 (Th1/Th2) immunocytokines (ICKs) in children with infectious mononucleosis (IM). METHODS: This is a retrospective study. A total of 40 children with IM treated in our hospital from August 2019 to August 2021 were included in the research group, and another 42 children with upper respiratory tract infection treated during the same period were selected as the control group. The VCA-IgM positive (+) rate and Th1/Th2 ICKs in two groups were detected, and the correlation of VCA-IgM with Th1/Th2 ICKs in IM patients was analyzed. RESULTS: The research group was found to have an evidently higher VCA-IgM+ rate than the control group. Moreover, the accuracy of VCA-IgM in detecting IM was as high as 91.46%. In addition, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-6 and IL-10 presented markedly elevated levels in the research group than in the control group, and in VCA-IgM negative (-) patients compared with VCA-IgM+ patients. There was a positive connection between VCA-IgM and Th1/Th2 ICKs. CONCLUSIONS: IM children showed high VCA-IgM+ rate and imbalance of Th1/Th2 ICKs, and their VCA-IgM and Th1/Th2 ICKs are positively correlated. In addition, VCA-IgM has certain diagnostic value for IM.

Intrathecal ultra-low dose naloxone enhances the antinociceptive effect of morphine by enhancing the reuptake of excitatory amino acids from the synaptic cleft in the spinal cord of partial sciatic nerve-transected rats.

BACKGROUND: In this study, we examined the effects of ultra-low dose naloxone on the antinociceptive effect of morphine and on spinal cord dorsal horn glutamate transporter expression in rats with neuropathic pain. METHODS: Neuropathic pain was induced in male Wistar rats by partial transection of the left sciatic nerve and an intrathecal catheter was implanted for drug administration; in some rats, an intrathecal microdialysis probe for cerebrospinal fluid (CSF) dialysate collection was also implanted. Nociception was assessed using the plantar test, a Hargreaves radiant heat apparatus, and by the von Frey test, using a dynamic plantar anesthesiometer. Glutamate transporter protein expression in the left spinal cord dorsal horn was examined by Western blotting and immunohistochemistry. Levels of the excitatory amino acids (EAAs) glutamate and aspartate in the CSF dialysate were measured using high-performance liquid chromatography. RESULTS: Reduced astrocyte expression of glutamate transporters (GLT-1 and GLAST levels were 55% and 53%, respectively, of that in sham-operated rats) in laminae I and II of the spinal cord dorsal horn ipsilateral to the partial sciatic nerve transection (PST), and hyperalgesia and allodynia in the PST hindlimb were observed. High-dose naloxone (15 µg) attenuated the antihyperalgesia and antiallodynia effects of the morphine (10 µg). In contrast, ultra-low dose (15 ng) naloxone enhanced the antinociceptive effect of morphine (10 µg), with an increase in the paw withdrawal threshold to thermal stimulus (from 19% to 35%) and to tactile stimulus (from 33% to 55%) compared with morphine treatment alone, and this was associated with restoration of GLAST and GLT-1 expression to control levels (102% and 114%, respectively) in the astrocytes of laminae I and II in the spinal cord dorsal horn ipsilateral to the PST hindlimb and a decrease in EAA levels in the CSF dialysate (glutamate: 10.0 µM; aspartate: 1.1 µM). CONCLUSIONS: Ultra-low dose naloxone enhanced the antinociceptive effect of morphine in PST rats, possibly by restoration of GLAST and GLT-1 expression in astrocytes, which inhibited the accumulation of EAAs in the synapses, resulting in a neuroprotective effect.

Integration of organic and inorganic photothermal probes for enhanced photothermometric sensing of silver ions.

A new signal-amplified photothermometric sensor of Ag+ was explored based on a simple yet effective integration of inorganic and organic photothermal probes, mainly depending on the successful exploitation of a dual-signal transduction channel originating from the inherent photothermal property and the peroxidase-like activity of Prussian blue nanocubes (PB NCs).

Effect of mesenchymal-epithelial transition amplification on immune microenvironment and efficacy of immune checkpoint inhibitors in patients with non-small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have brought clinical benefits to patients with various histological types of lung cancer. Previous studies have shown an association between mesenchymal-epithelial transition (MET) and the immunotherapy response in non-small cell lung cancer (NSCLC) but there is a lack of clinical data on the correlation of MET amplification with the ICI response in NSCLC. METHODS: Copy number alteration (CNA), somatic mutation, and clinical data from two immunotherapy cohorts (Rizvi et al. cohort and our local cohort) were collected and pooled to further investigate the key role of MET amplification in patients with NSCLC receiving ICIs. The correlations between MET amplification and tumor immunogenicity and antitumor immunity were further investigated in The Cancer Genome Atlas (TCGA)-NSCLC [lung adenocarcinoma (LUAD)/lung squamous cell carcinoma (LUSC)] data-set. RESULTS: In the immunotherapy cohorts, MET amplification was associated with longer progression-free survival (PFS) times in patients receiving ICI treatment (P=0.039; HR =0.37; 95% CI: 0.18-0.73). In the TCGA-NSCLC data-set, MET amplification was associated with high MET mRNA and protein levels, tumor mutation burden (TMB), neoantigen load (NAL), immune-activated cell patterns, immune-related gene expression levels, and the number of gene alterations in the DNA damage response and repair (DDR) pathway. Gene set enrichment analysis (GSEA) results indicated significant up-regulation of the immune response-related pathways in the MET-amplification group. CONCLUSIONS: Our results suggest that MET amplification may be a novel predictive marker for immunotherapy efficacy in NSCLC.

In-situ synthesis of calcium borate/cellulose acetate-laurate nanocomposite as efficient extreme pressure and anti-wear lubricant additives.

In this study, calcium borate (CB) nanoparticles were in-situ grown onto cellulose acetate-laurate (CAL) template to prepare CB/CAL nanocomposite with uniform dispersion of CB nanoparticles by hydrothermal method. As-prepared CB/CAL nanoparticles were characterized by field emission scanning electron microscope, Fourier transforms infrared spectrometry, X-ray diffraction, and energy-dispersive X-ray spectroscopy. With average wear scar diameter (WSD), coefficient of friction (COF) and maximum non-seizure load (PB) as evaluation criterions, CB/CAL, CAL, and CB were used as lubricant additives in poly-alpha-olefin (PAO) base oil to comparatively investigate the tribological properties with a four-ball tribotester. It was found that under the load of 490 N, the WSD and COF of PAO + CB/CAL (concentration of 0.6 wt%) reduced by 25.9% and 48.7%, respectively, and PB increased by 79.6% compared with pure PAO base oil. CB/CAL nanocomposite exhibited superior lubricating performances than CB and CAL. In addition, the synergistic lubricating mechanism of CB/CAL nanocomposite as lubricant additive was explored.

Efficacy and safety of concurrent anti-tuberculosis treatment and chemotherapy in lung cancer patients with co-existent tuberculosis.

BACKGROUND: This retrospective study evaluated the safety and efficacy of concurrent anti-tuberculosis (TB) and chemotherapy treatment in patients with advanced lung cancer and active TB. METHODS: We retrospectively analyzed patients who were first diagnosed with advanced lung cancer and received first-line chemotherapy in Guangzhou Chest Hospital from 2015 to 2017. Patients were categorized into two groups (2:1): lung cancer patients without active TB (Group A), and lung cancer patients with active TB (Group B). Primary endpoints included adverse events (AEs), objective response rate (ORR), time to treatment failure, and overall survival (OS). RESULTS: A total of 99 patients were eligible (Group A, n=66; Group B, n=33). Grade ≥3 treatment-related AEs, primarily hematologic toxicity, occurred in 39.4% and 51.5% of patients in Groups A and B, respectively. The hypohepatia in both groups was generally at grade 1 or 2, with similar incidences (26% and 27%, respectively). After two cycles of chemotherapy, the ORR was 42.4% and 33.3% in Group A and B, respectively (P=0.383). The median time to treatment failure (TTF) was 7.0 and 5.6 months for Groups A and B, respectively (P=0.175). The median OS was 17.0 and 14.0 months for Groups A and B, respectively (P=0.312). After 3 months of anti-TB treatment, all patients achieved sputum acid-fast bacilli (AFB) smear conversion and absorption on imaging, and the end of follow-up observed no recurrence. CONCLUSIONS: Concurrent anti-TB and chemotherapy treatment did not increase hematological toxicity or hypohepatia in lung cancer patients with pulmonary TB.

Effects of Lactobacillus plantarum PS128 on Children with Autism Spectrum Disorder in Taiwan: A Randomized, Double-Blind, Placebo-Controlled Trial.

This four-week, randomized, double-blind, placebo-controlled study investigated the effects of Lactobacillus plantarum PS128 (PS128) on boys with autism spectrum disorder (ASD) aged 7-15 in Taiwan. All subjects fulfilled the criteria for ASD diagnosis of DSM-V and the Autism Diagnostic Interview-Revised (ADI-R). Questionnaires used for the primary outcome measure include the Autism Behavior Checklist-Taiwan version (ABC-T), the Social Responsiveness Scale (SRS) and the Child Behavior Checklist (CBCL). The Swanson, Nolan, and Pelham-IV-Taiwan version (SNAP-IV) and the Clinical Global Impression-improvement (CGI-I) were used for the secondary outcome measure. The results showed that PS128 ameliorated opposition/defiance behaviors, and that the total score of SNAP-IV for younger children (aged 712) improved significantly compared with the placebo group. Additionally, several elements were also notably improved in the PS128 group after 28-day consumption of PS128. Further studies are needed to better clarify the effects of PS128 for younger children with ASD on broader symptoms.

Tumor Mutational Burden and Genomic Alterations in Chinese Small Cell Lung Cancer Measured by Whole-Exome Sequencing.

PURPOSE: Studies on genetic alterations of the heterogenous small cell lung cancer (SCLC) are rare. We carried out the present study to clarify the genomic alterations and TMB levels of Chinese SCLC patients by whole-exome sequencing. MATERIALS AND METHODS: Whole-exome sequencing by next-generation sequencing technique was implemented on twenty SCLC samples. Significant somatic mutations and copy number variations were screened, followed by comparison with the data extracted from COSMIC. Besides, altered signaling pathways were examined in order to figure out actionable targets. RESULTS: A total of 8,062 nonsynonymous mutations were defined. The number of mutations for each case ranged from 98 to 864. As for base substitutions, a total of 15,817 substitutions were detected with C > A conversion which was correlated to smoking occupying 25.57%. The TMB values ranged from 2.51/Mb to 22.1/Mb with a median value of 9.95/Mb. RB1 was the most frequently mutated gene altered in 18 (90%) cases, followed by TP53 altered in 17 (85%) cases. Other commonly changed genes were PTEN, and RBL1, with frequencies of 55% and 50%, respectively. SOX2 significantly amplified in 6 (30%) cases and MYCN amplified in 1 (5%) patient. Notch signaling pathway and PI3K/AKT/mTOR signaling pathway were universally and significantly changed. Major genomic alterations were in consistency with data from COSMIC, but frequencies of less common mutations were different. CONCLUSION: TP53 and RB1 inactivations were universally detected in SCLC. The Notch and PI3K/AKT/mTOR signaling pathways were both significantly altered, implying potential actionable targets.