Effectiveness and safety of thoracic manipulation in the treatment of neck pain: An updated systematic review and meta-analysis.

BACKGROUND: The purpose of this meta-analysis was to evaluate the effectiveness and safety of thoracic manipulation (TM) in patients with neck pain (NP). OBJECTIVE: The purpose of this meta-analysis was to evaluate the effectiveness and safety of thoracic manipulation (TM) in patients with neck pain (NP). METHODS: Seven electronic databases were searched from their inception through October 2023 by two authors. The methodological quality assessments were performed with the Physiotherapy Evidence Database (PEDro) scale. Pain, cervical range of motion (ROM), disability, and quality of life (QOL) were estimated for TM treatment in patients with NP. RESULTS: Eighteen randomized controlled trials (RCTs) with 914 patients were included with a PEDro score of 6.923 ± 3.120. Pooled effect sizes of pain (SMD =-0.481, 95% CI -0.653 to -0.309, P= 0.000), disability (SMD =-1.435, 95% CI -2.480 to -0.390, P= 0.007), QOL-physical component score (PCS) (SMD = 0.658, 95% CI 0.290 to 1.025, P= 0.000), ROM of flexion (SMD = 0.921, 95% CI 0.287 to 1.555, P= 0.000), ROM of extension (SMD = 0.572, 95% CI 0.321 to 0.822, P= 0.000), ROM of left lateral flexion (SMD = 0.593, 95% CI 0.075 to 1.112, P= 0.025) and ROM of left rotation (SMD = 0.230, 95% CI 0.010 to 0.450, P= 0.04) were favored by the TM group. CONCLUSIONS: TM provides short-term effect on relieving neck pain, increasing cervical ROM, and disability in patients with NP without serious side effects. Continuous therapy and distraction therapy are recommended as optimal choice on reducing pain and improving cervical ROM, especially in patients with chronic NP (> 3 months). The TM-induced improvements in the QOL of patients with NP should be verified by more further high-quality RCTs.

Selenochemical modification of low molecular weight polysaccharides from Grifola frondosa and the mechanism of their inhibitory effects on gastric cancer cells.

An important micronutrient involved in immune response and antitumor is selenium. LMW-GFP, a polysaccharide extracted from Grifola frondosa seed bodies, has a relatively weak antitumor effect on BGC-823 and MFC cells in vitro, whereas selenium binding to LMW-GFP can significantly increase the in vitro antitumor activity of LMW-GFP. In this study, Se-LMW-GFP was prepared by the HNO3-Na2SeO3 method, and the structures of LMW-GFP and Se-LMW-GFP were characterized by UV-visible spectroscopy of absorption, FTIR spectroscopy, and electron scanning microscopy, and these structural analyses showed that selenium was successfully complexed to LMW-GFP. The selenium content of Se-LMW-GFP was measured to be 2.08 % ± 0.08 % by ICP-MS. The anti-tumor activity of LMW-GFP before and after selenium modification was compared by cellular experiments, and the findings indicated that the anti-tumor activity of Se-LMW-GFP was considerably improved over that of LMW-GFP, and inhibited the proliferation of BGC-823 cells and MFC cells through a combination of the Fas/FasL-mediated exogenous death receptor pathway as well as the endogenous mitochondrial pathway. Our results suggest that Se-LMW-GFP not only has great potential for natural health food and anti-gastric cancer drug development but is also a good selenium supplement.

Corneal Biomechanical Characteristics in Myopes and Emmetropes Measured by Corvis ST: A Meta-Analysis.

PURPOSE: To comprehensively identify the corneal biomechanical differences measured by Corvis ST between different degrees of myopia and emmetropia. DESIGN: Systematic review and meta-analysis. METHODS: Electronic databases, including PubMed, Embase, and Web of Science, were systematically searched for studies comparing the corneal biomechanics among various degrees of myopes and emmetropes using Corvis ST. The weighted mean differences and 95% confidence intervals were calculated. Meta-analysis was performed in high and nonhigh myopes and in myopes and emmetropes, respectively. RESULTS: Eleven studies were included in this study. The meta-analysis among myopes and emmetropes included 1947 myopes and 621 emmetropes, and 443 high myopes and 449 nonhigh myopes were included in the meta-analysis among high and nonhigh myopia. Myopes showed the cornea with significantly longer time at the first applanation (A1t) and lower length at the second applanation (A2L) than emmetropes. High myopes showed significantly greater A1t, velocity at the second applanation (A2v), deformation amplitude at the highest concavity (HC-DA), and peak distance at the highest concavity (HC-PD) and decreased time at the second applanation (A2t) and radius of the highest concavity (HC-R). CONCLUSIONS: Corneal biomechanics is different in myopia, especially in high myopia. Compared with nonhigh myopes, the corneas of high myopes deformed slower during the first applanation, faster during the second applanation, and showed greater deformation amplitude, indicating greater elasticity and viscidity.

Dynamics of SARS-CoV-2 IgG antibodies and neutralising antibodies in rheumatic and musculoskeletal diseases patients with COVID-19.

OBJECTIVES: Rheumatic and musculoskeletal diseases (RMD) may exhibit different immune responses to novel coronavirus (COVID-19) infection compared to healthy individuals. While previous studies have primarily investigated changes in COVID-19-related antibodies post-vaccination for RMD patients, this study sought to explore the dynamics of SARS-CoV-2 IgG antibodies and neutralising antibodies (NAb) in RMD patients after COVID-19 infection. METHODS: In this longitudinal study, we monitored the SARS-CoV-2 IgG antibodies and NAb levels in RMD patients and healthy controls (HC) at 60 and 90 days post-COVID-19 infection. Chemiluminescent immunoassay was used to detect the levels of novel coronavirus-specific IgG (anti-S1/S2 IgG) antibodies and NAb. RESULTS: A total of 292 RMD patients and 104 HC were enrolled in the study. At both the 60-day and 90-day post-COVID-19 infection, RMD patients exhibited significantly lower levels of anti-S1/S2 IgG and NAb than those in the HC group (p<0.001). The anti-S1/S2 IgG antibody levels remained relatively stable, while the NAb levels in RMD patients could vary greatly between the 60th and 90th days. A logistic regression analysis revealed that the prior administration of glucocorticoids (GC), immunosuppressants, and b/tsDMARDs stood out as independent risk factors associated with reduced anti-S1/S2 IgG and NAb levels, irrespective of the specific RMD subtypes. CONCLUSIONS: GC and anti-rheumatic medications can potentially alter the production of specific antibodies, especially NAb, in RMD patients post-COVID-19 infection. These findings emphasise the importance of continuous monitoring for NAb fluctuations in RMD patients following a COVID-19 infection.

A New Perspective in the Treatment of Ischemic Stroke: Ferroptosis.

Ischemic stroke is a common neurological disease. Currently, there are no Food and Drug Administration-approved drugs that can maximize the improvement in ischemic stroke-induced nerve damage. Hence, treating ischemic stroke remains a clinical challenge. Ferroptosis has been increasingly studied in recent years, and it is closely related to the pathophysiological process of ischemic stroke. Iron overload, reactive oxygen species accumulation, lipid peroxidation, and glutamate accumulation associated with ferroptosis are all present in ischemic stroke. This article focuses on describing the relationship between ferroptosis and ischemic stroke and summarizes the relevant substances that ameliorate ischemic stroke-induced neurological damage by inhibiting ferroptosis. Finally, the problems in the treatment of ischemic stroke targeting ferroptosis are discussed, hoping to provide a new direction for its treatment.

Polymorphonuclear myeloid-derived suppressor cells and phosphatidylinositol-3 kinase gamma are critical to tobacco-mimicking oral carcinogenesis in mice.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a devastating disease most often associated with tobacco consumption that induces a field of mutations from which a tumor arises. Identification of ways to prevent the emergence of cancer in high-risk patients is an ultimate goal for combatting all types of cancer, including OSCC. METHODS: Our study employs a mouse model of tongue carcinogenesis induced by tobacco carcinogen mimetic, 4-nitroquinoline 1-oxide (4NQO), to establish tongue dysplasia and OSCC. We use conventional histology, immunohistochemistry, multispectral imaging, mass cytometry, novel cell lines, pharmaceutical inhibition of PI3Kγ, T-cell suppression assays and mouse transplant models in our functional experimentation. RESULTS: In our study, we identify Ly6G+ granulocytes as the most abundant immune cell type in a model of tongue carcinogenesis induced by tobacco carcinogen mimetic 4NQO. Targeting Ly6G+ granulocytes with a pharmacologic inhibitor of PI3Kγ, an isoform of PI3K exclusively expressed by myeloid cells, resulted in reduced tongue dysplasia severity, and reduced rates of OSCC. Importantly, we performed functional assays with the Ly6G+ granulocytes induced in cell line models of 4NQO carcinogenesis to demonstrate that these granulocytes have increased polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) activity against T-cell proliferation and these PMN-MDSCs play a functional role in promoting tumor formation by inhibiting tumor regression in a PI3Kγ-dependent manner. CONCLUSIONS: Overall, our data suggest that recruitment of PMN-MDSCs to sites of dysplasia is critical to immune suppression of CD8 T cells, thereby permitting malignancy, and PI3Kγ inhibitors are one mechanism to reduce PMN-MDSC recruitment, immunosuppression and tumorigenesis in OSCC.

Reproductive Factors and the Risk of Open Angle Glaucoma in Women.

PRCIS: There was a significant inverse linear relationship between age at menopause and open angle glaucoma (OAG). Late menarche (≥13 y) and a history of 5 or more deliveries were significantly associated with an increased risk of OAG. PURPOSE: To determine the association between reproductive factors including age at menarche, age at menopause, reproductive period, parity, and the risk of OAG in women. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were searched until February 9, 2022. Studies were included if they assessed the association between reproductive factors and OAG. The adjusted odds ratios (ORs) with relevant 95% CIs were extracted and pooled using fixed-effects models. Besides, we conducted dose-response analyses via the generalized least squares for trend method. RESULTS: Seven articles including 18,618 women were identified in this review. The pooled results indicated that late age at menarche (≥13 y) was significantly associated with an increased risk of OAG (OR=1.76, 95% CI: 1.28, 2.43). Early menopause (<45 y) also significantly elevated the risk of OAG (OR=1.89, 95% CI: 1.23, 2.90) in categorical meta-analyses, consistent with the inverse linear relationship between menopausal age and the risk of OAG in dose-response analyses ( P =0.002). In addition, women who had delivered at least 5 children were at significantly higher risk of OAG compared with those nulliparous (OR=2.35, 95% CI: 1.02, 5.39), and a J-shape relationship between parity and OAG was observed in dose-response analyses ( P <0.001). CONCLUSIONS: Late menarche (≥13 y), early menopause (<45 y), and a history of 5 or more parturitions are possible risk factors for OAG. Longitudinal studies are warranted to further examine the relationships between reproductive factors and the risk of OAG.

Inducible nitric oxide synthase (iNOS)-activated Cxcr2 signaling in myeloid cells promotes TGFß-dependent squamous cell carcinoma lung metastasis.

Transforming growth factor beta (TGFß) activity is linked to metastasis in many cancer types, but whether TGFß activity is necessary for squamous cell carcinoma (SCC) lung metastasis has not been studied. Here we used a lung metastatic SCC model derived from keratin 15 (K15). KrasG12D.Smad4-/- SCC and human SCC specimens to identify metastasis drivers and test therapeutic interventions. We demonstrated that a TGFß receptor (TGFßR) inhibitor reduced lung metastasis in mouse SCC correlating with reduced CD11b+/Ly6G+ myeloid cells positive for inducible nitric oxide synthase (iNOS). Further, TGFß activity and iNOS were higher in primary human oral SCCs with metastasis than SCCs without metastasis. Consistently, either depleting myeloid cells with anti-Gr1 antibody or inhibiting iNOS with L-N6-(1-iminoethyl)-l-lysine (L-NIL) reduced SCC lung metastasis. L-NIL treated tumor-bearing mice exhibited reductions in tumor-infiltrating myeloid cells and in plasma Cxcl5 levels, and attenuated primary tumor growth with increased apoptosis and decreased proliferation. Blocking Cxcl5 with an antagonist of its receptor Cxcr2, SB225002, also reduced SCC lung metastasis.

IL-22RA2 Is a SMAD7 Target Mediating the Alleviation of Dermatitis and Psoriatic Phenotypes in Mice.

Long-term management of inflammatory skin diseases is challenging because of side effects from repeated use of systemic treatments or topical corticosteroids. This study sought to identify the mechanisms and developmental therapeutics for these diseases using genetic models and pharmacological approaches. We found that mice overexpressing SMAD7 in keratinocytes but not mice overexpressing the N-terminal domain of SMAD7 (i.e., N-SMAD7) were resistant to imiquimod-induced T helper 1/17- and T helper 2-type inflammation. We generated a Tat-PYC-SMAD7 (truncated SMAD7 protein encompassing C-terminal SMAD7 and PY motif fused with cell-penetrating Tat peptide). Topically applied Tat-PYC-SMAD7 to inflamed skin entered cells upon contact and attenuated imiquimod-, 2,4-dinitrofluorobenzene-, and tape-stripping-induced inflammation. RNA-sequencing analyses of mouse skin exposed to these insults showed that in addition to inhibiting TGFß/NF-κB, SMAD7 blunted IL-22/signal transducer and activator of transcription 3 activation and associated pathogenesis, which is due to SMAD7 transcriptionally upregulating IL-22 antagonist IL-22RA2. Mechanistically, SMAD7 facilitated nuclear translocation and DNA binding of C/EBPß to IL22RA2 promoter for IL22RA2 transactivation. Consistent with the observations in mice mentioned earlier, transcript levels of IL22RA2 were increased in human atopic dermatitis and psoriasis lesions with clinical remission. Our study identified the anti-inflammation functional domain of SMAD7 and suggests the mechanism and feasibility for developing SMAD7-based biologics as a topical therapy for skin inflammatory disorders.

Identification of natural compound garcinone E as a novel autophagic flux inhibitor with anticancer effect in nasopharyngeal carcinoma cells.

CONTEXT: Current chemotherapeutic drugs cannot meet the treatment needs of patients with nasopharyngeal carcinoma (NPC), so urgent action is needed to discover novel chemotherapeutic agents. Our previous study revealed that garcinone E (GE) inhibited the proliferation and metastasis of NPC, suggesting that the compound might display promising anticancer activity. OBJECTIVE: To examine the mechanism underlying the anti-NPC activity of GE for the first time. MATERIALS AND METHODS: For MTS assay, NPC cells were treated with 2.5-20 µmol/L GE or dimethyl sulfoxide for 24, 48, and 72 h. Colony formation capacity, cell cycle distribution, and in vivo xenograft experiment of GE were assessed. MDC staining, StubRFP-sensGFP-LC3 observation, LysoBrite Blue staining, and immunofluorescence examined the autophagy of NPC cells after GE exposure. Western blotting, RNA-sequencing, and RT-qPCR measured protein and mRNA levels. RESULTS: GE suppressed cell viability with an IC50 of 7.64, 8.83 and 4.65 µmol/L for HK1, HONE1 and S18 cells. GE inhibited colony formation and cell cycle, increased autophagosome number, and inhibited the autophagic flux partially by blocking lysosome-autophagosome fusion, and repressed S18 xenograft growth. GE dysregulated the expression of autophagy- and cell cycle-related proteins such as Beclin-1, SQSTM1/p62, LC3, CDKs, and Cyclins. Bioinformatics GO and KEGG pathway enrichment analysis of RNA-seq showed that autophagy was enriched in differentially expressed genes upon GE treatment. DISCUSSION AND CONCLUSION: GE acts as an autophagic flux inhibitor, which may have potential chemotherapeutic use for NPC treatment and may have an application in basic research to explore the mechanisms of autophagy.

[Holocarboxylase synthetase deficiency induced by HLCS gene mutations: a rare disease study]. / ç½•è§ç— ç ”ç©¶ï¼šHLCSåŸºå› çªå˜è‡´å ¨ç¾§åŒ–é ¶åˆæˆé ¶ç¼ºä¹ç—‡.

A boy, aged 16 months, attended the hospital due to head and facial erythema for 15 months and vulva erythema for 10 months with aggravation for 5 days. The boy developed perioral and periocular erythema in the neonatal period and had erythema and papules with desquamation and erosion in the neck, armpit, and trigone of vulva in infancy. Blood gas analysis showed metabolic acidosis; the analysis of amino acid and acylcarnitine profiles for inherited metabolic diseases and the analysis of organic acid in urine suggested multiple carboxylase deficiency; genetic testing showed a homozygous mutation of c.1522C>T(p.R508W) in the HLCS gene. Finally the boy was diagnosed with holocarboxylase synthetase deficiency and achieved a good clinical outcome after oral biotin treatment. This article analyzes the clinical data of a child with holocarboxylase synthetase deficiency and summarizes the etiology, diagnosis, and treatment of this child, so as to provide ideas for clinicians to diagnose this rare disease.

Structural characteristics of a low molecular weight velvet antler protein and the anti-tumor activity on S180 tumor-bearing mice.

Velvet antler is a traditional Chinese medicine with various pharmacological values, which is an important raw material for traditional Chinese medicinal wine. Nevertheless, the chemical compositions and bioactivities of velvet antler residue used for making medicinal wine are rarely reported, leading to a waste of resources. In this study, a velvet antler protein (VA-pro) was extracted from velvet antler residue by simulating the gastrointestinal digestion, and its composition, structural characteristics and in vivo anti-tumor activities were determined and investigated. VA-pro possessed high purity with a relatively low molecular weight as 22.589 kDa under HPLC, one- and two-dimensional electrophoresis, and it contained high contents of Pro, Gly, Glu and Ala. Besides, the secondary structure of VA-pro was dominated by ß-turn and ß-sheet, and VA-pro possessed similar protein sequence, isoelectric point and amino acid compositions to hypothetical protein G4228_020061. The in vivo results substantiated that VA-pro could improve the body weights and immune organ indices, increase the expressions of sera cytokines and regulate the distributions of T and B lymphocytes subsets in peripheral blood of S180 tumor-bearing mice. Furthermore, VA-pro could effectively inhibit solid S180 tumors growth by inducing S phase cell cycle arrest mediated through mitochondria. To summarize, our study provided theoretical support that VA-pro had the potential to be used as an immunopotentiator in immunocompromised or cancer-bearing hosts.

Efficacy and safety of proprioceptive neuromuscular facilitation for chronic low back pain: A meta-analysis of randomized controlled trials.

Objectives: This study aimed to evaluate the effectiveness and safety of proprioceptive neuromuscular facilitation for chronic low back pain.Materials and methods: Eleven databases were searched from their inception through January 2021. The primary outcomes were pain intensity, individual activities, quality of life, and adverse events. Results: Four randomized controlled trials (RCTs) with 184 patients (mean age: 37.8±3.1 years; range, 35 to 50 years) met the inclusion criteria. The pooled effect size showed proprioceptive neuromuscular facilitation, relieved pain (standard means difference [SMD]: -0.835, 95% CI: -1.139 to -0.531, p<0.001, n=4), and improved individual activity (Roland Morris Disability Questionnaire, SMD: -1.765, 95% CI: -2.642 to -0.888, p<0.001, n=2; Oswestry Disability Index, SMD: -0.893, 95% CI: -1.434 to -0.352, p=0.001, n=1) for chronic low back pain (CLBP). Conclusion: This study verified that proprioceptive neuromuscular facilitation could relieve pain and improve individual activities without serious adverse events in patients with CLBP; however, it should be cautiously recommended due to the small number of included RCTs.

Smoking, dietary factors and major age-related eye disorders: an umbrella review of systematic reviews and meta-analyses.

BACKGROUND: There is accumulating evidence of the associations between age-related eye diseases (AREDs) and smoking or dietary factors. We aimed to provide an umbrella review of the published literature pertaining to smoking or dietary intake as risk factors for major AREDs including cataract, glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy. METHODS: We searched for pertinent systematic reviews or meta-analyses in PubMed and Web of Science until 16 April 2022. We reperformed the meta-analysis of each association using random effects models. The heterogeneity and 95% prediction interval were calculated. The presence of small-study effect or excess significance bias was also assessed. RESULTS: In total, 64 associations from 25 meta-analyses and 41 associations from 10 qualitative systematic reviews were evaluated. There was convincing (class I) evidence for only one association, namely current smoking and cataract. Two factors had highly suggestive (class II) evidence, namely ever smoking associated with cataract and fish consumption associated with AMD. We also found suggestive (class III) evidence for associations between the dietary intake of omega-3 polyunsaturated fatty acid, lutein, zeaxanthin, vitamin C and the risk of cataract. CONCLUSIONS: Smoking as a risk factor for cataract was the most robust association we identified. We also identified several dietary elements associated with AREDs. Large prospective studies are warranted to further examine the associations discussed in this review. PROSPERO REGISTRATION NUMBER: CRD42022339082.

The effects of Clostridium butyricum on Ira rabbit growth performance, cecal microbiota and plasma metabolome.

Clostridium butyricum (C. butyricum) can provide many benefits for animals' growth performance and gut health. In this study, we investigated the effects of C. butyricum on the growth performance, cecal microbiota, and plasma metabolome in Ira rabbits. A total of 216 Ira rabbits at 32 days of age were randomly assigned to four treatments supplemented with basal diets containing 0 (CG), 200 (LC), 400 (MC), and 600 mg/kg (HC) C. butyricum for 35 days, respectively. In comparison with the CG group, C. butyricum supplementation significantly improved the average daily gain (ADG) and feed conversion rate (FCR) at 53 and 67 days of age (P < 0.05) and digestibilities of crude protein (CP) and crude fiber (CF) at 67 days of age (P < 0.05). The cellulase activity in the HC group was higher respectively by 50.14 and 90.13% at 53 and 67 days of age, than those in the CG groups (P < 0.05). Moreover, at 67 days of age, the diet supplemented with C. butyricum significantly increased the relative abundance of Verrucomicrobia at the phylum level (P < 0.05). Meanwhile, the concentrations of different metabolites, such as amino acids and purine, were significantly altered by C. butyricum (P < 0.05). In addition, 10 different genera were highly correlated with 52 different metabolites at 53-day-old and 6 different genera were highly correlated with 18 different metabolites at 67-day-old Ira rabbits. These findings indicated that the C. butyricum supplementation could significantly improve the growth performance by modifying the cecal microbiota structure and plasma metabolome of weaned Ira rabbits.

Status of linusorbs in cold-pressed flaxseed oil during oxidation and their response toward antioxidants.

Linusorbs (LOs, cyclolinopeptides) are a class of naturally occurring cyclic hydrophobic peptides found in flaxseed oil, whose oxidation states indicate the oxidative stability and bitterness of flaxseed oil. Subjected to 63 °C accelerated oxidation, most Met-containing LOs in cold-pressed flaxseed oil entirely depleted by the 6th day except CLP, and MetO2-containing LOs became the dominant ones. However, no MetO2 form of Trp-containing LOs, such as CLD, CLF and CLG, were detected. Given their oxidative kinetics, methionine sulfoxide (MetO) residue in some LOs was less sensitive toward oxidation in the presence of Trp (Tryptophan) group, and the oxidative stability of Met-containing LOs was CLP < CLB < CLL ≈ CLM < CLO, as compared to MetO-containing LOs: CLD < CLE < CLC < CLF ≈ CLG. When antioxidant was added into cold-pressed flaxseed oil to assess the additives' antioxidant effect, no significant difference was observed on oil oxidative indices in early stage except α-tocopherol, where they vary dramatically in suppressing Met oxidation of LOs: L-AP (L-ascorbyl palmitate) > TBHQ (tert-butyl hydroquinone) > Î³-tocopherol > carnosic acid > α-tocopherol. Besides its ability to suppress oxidation of Trp-containing LOs, L-AP also exhibits superior antioxidant effect on non-Trp-containing LOs due to its amphiphilic property. Due to the prooxidative effects of both α- and γ-tocopherol on LOs that contain Trp, it has been suggested that tocopherols may repair Trp residue on LOs, leading to increased tendency of MetO residues to oxidize. The findings of this research are critical for elucidating the antioxidative mechanism of LOs, which can further lead to the establishment of strategies in suppressing bitter after taste to produce high-quality flaxseed oil.

[Recurrent systemic sporadic rash for 10 years in a girl aged 11 years]. / 11å²å¥³å­©åå¤å ¨èº«æ•£åœ¨çš®ç–¹10å¹´.

A girl, aged 11 years, was admitted due to recurrent rash on the whole body and mucosa for 10 years, and typical rash was erythema at the perioral region, hand-foot joints, vulva, and perianal region, with blisters, erosions, and ulcers on the erythema. The girl was improved after zinc supplementation. Her younger brother had similar rash and medical history. The histopathological examination showed epidermal parakeratosis with mild hyperkeratosis, severe spongiform edema of the stratum corneum, significant proliferation of acanthocytes, and vacuolation of keratinocytes. The genetic testing revealed that both the girl and her younger brother had a homozygous mutation of c.1456(exon9)delG in the SLC39A4 gene, and thus the girl was diagnosed with acrodermatitis enteropathica. It is concluded that for children with recurrent rash on the limbs and at the perioral region, genetic testing should be performed as early as possible to make a confirmed diagnosis, and a sufficient dose of zinc supplementation should be given, while the levels of trace elements such as blood zinc should be regularly monitored.

Brain-Reactive Antibodies are Potential Biomarkers for Evaluating Therapeutic Efficacy in NPSLE Patients.

Purpose: Neuropsychiatric systemic lupus erythematosus (NPSLE) is the main cause of disability and death in systemic lupus erythematosus (SLE). It can cause cognitive impairment and organic brain syndrome. Brain-reactive antibodies, such as anti-DNA/anti-N-methyl-D-aspartate receptor (NMDAR) antibodies (DNRAbs), anti-microtubule-associated protein 2 (anti-MAP2) antibodies, and anti-glial fibrillary acidic protein (anti-GFAP) antibodies are thought to participate in the progression of NPSLE and thus considered potential diagnostic biomarkers, but whether they can be used for evaluating therapeutic efficacy in NPSLE is unknown. Patients and methods: Overall, 17 NPSLE patients and 10 non-SLE controls were included in this study. All the patients were treated with glucocorticoid (GC) pulse therapy. Serum and cerebrospinal fluid (CSF) concentrations of DNRAbs and anti-MAP2 and anti-GFAP antibodies were measured using enzyme-linked immunosorbent assay. The differences between the CSF concentrations of these antibodies in NPSLE patients before and after GC pulse therapy were analyzed. Results: CSF concentrations of DNRAbs and anti-MAP2 and anti-GFAP antibodies were significantly higher in NPSLE patients compared to the non-SLE controls. Among the patients, CSF concentration of DNRAbs was significantly higher in the patients with acute confusional state (ACS) than in those with non-ACS diffuse NPSLE or focal NPSLE. Additionally, CSF concentration of DNRAbs was significantly correlated with QIgG (r=0.4884, P=0.0467) and IgG index (r=0.5319, P=0.0280) in NPSLE patients. Moreover, CSF concentrations of DNRAbs, anti-MAP2, and anti-GFAP antibodies and QIgG were significantly decreased after GC pulse therapy in NPSLE patients. Conclusion: These results indicate that CSF DNRAbs and anti-MAP2 and anti-GFAP antibodies are potential biomarkers for evaluating therapeutic efficacy in NPSLE.

Differential responses to immune checkpoint inhibitor dictated by pre-existing differential immune profiles in squamous cell carcinomas caused by same initial oncogenic drivers.

BACKGROUND: While immune checkpoint inhibitors (ICI) were approved for head and neck squamous cell carcinomas (HNSCCs), the response rate remains relatively low. Mechanisms underlying ICI unresponsiveness versus sensitivity are not fully understood. METHOD: To better delineate differential responses to ICI treatment, we employed mouse SCC models, termed KPPA tumors that were caused by deleting p53 and hyperactivating PIK3CA, two most frequently mutated genes in human HNSCCs. We transplanted two KPPA tumor lines (TAb2 versus TCh3) into C57BL/6 recipients and examined the immune tumor microenvironment using flow cytometry. Furthermore, we employed single-cell RNA sequencing to identify the difference in tumor infiltrating lymphocytes (TILs). RESULTS: We found that different KPPA tumors exhibited heterogeneous immune profiles pre-existing treatment that dictated their sensitivity or unresponsiveness to anti-PD-L1. Unresponsive TAb2 tumors were highly enriched with functional tumor-associated macrophages (TAMs), especially M2-TAMs. In contrast, sensitive TCh3 tumors contained more CD8 TILs with better effector functions. TAb2 tumor cells drastically expanded F4/80+ TAMs from bone marrow precursors, requiring CSF1 and VEGF. Consistently, a higher combined expression of VEGF-C and CSF1 predicts worse survival in PIK3CAAmp/TP53Mutated HNSCC patients. Unresponsive TAb2 tumors upregulated distinct signaling pathways that correlate with aggressive tumor phenotypes. While anti-PD-L1 did not affect the TME of TAb2 tumors, it significantly increased the number of CD8 TILs in TCh3 tumors. CONCLUSIONS: We uncovered tumor-intrinsic differences that may underlie the differential responses to ICI by establishing and employing two SCC tumor lines, TAb2 vs. TCh3, both of which harbor TP53 deletion and PIK3CA hyperactivation. Our study indicates the limitation of stratifying cancers according to their genetic alterations and suggests that evaluating HNSCC tumor-intrinsic cues along with immune profiles in the TME may help better predict ICI responses. Our experimental models may provide a platform for pinpointing tumor-intrinsic differences underlying an immunosuppressive TME in HNSCCs and for testing combined immunotherapies targeting either tumor-specific or TAM-specific players to improve ICI efficacy.

Preparation, Antioxidant and Immunoregulatory Activities of a Macromolecular Glycoprotein from Salvia miltiorrhiza.

Salvia miltiorrhiza has exhibited various bioactive functions due to the existence of polysaccharides, hydrophilic phenolic acids, diterpenoid quinones, and essential oils. However, little research has reported the glycoprotein preparation and corresponding bioactivities. In this study, the water-soluble glycoprotein from S. miltiorrhiza roots was firstly isolated with the extraction process optimized by response surface methodology, and then, the preliminary structural properties, and the antioxidant and immunoregulatory activities were investigated. Results showed that the extraction conditions for higher extraction yields were identified as follows: ultrasonic power of 220 W, ultrasonic time of 2.0 h, extraction temperature of 60 °C, liquid/solid ratio of 20 mL/g, and the glycoprotein yields of 1.63 ± 0.04%. Structural analysis showed that the glycoprotein comprised protein and polysaccharide (contents of 76.96% and 20.62%, respectively), with an average molecular weight of 1.55 × 105 Da. Besides, bioactivities analysis showed that the glycoprotein presented strong scavenging effects on multiple free radicals, and effectively enhanced the antioxidant enzyme activities and immunological indicators in cyclophosphamide-induced immunocompromised mice dose-dependently. These data demonstrated that S. miltiorrhiza glycoprotein presented the potential to be a novel edible functional compound, and could be practically applied in the food industry.