BPOZ-2 is a negative regulator of the NLPR3 inflammasome contributing to SARS-CoV-2-induced hyperinflammation.

Introduction: Inflammation play important roles in the initiation and progression of acute lung injury (ALI), acute respiratory distress syndrome (ARDS), septic shock, clotting dysfunction, or even death associated with SARS-CoV-2 infection. However, the pathogenic mechanisms underlying SARS-CoV-2-induced hyperinflammation are still largely unknown. Methods: The animal model of septic shock and ALI was established after LPS intraperitoneal injection or intratracheal instillation. Bone marrow-derived macrophages (BMDMs) from WT and BPOZ-2 KO mouse strains were harvested from the femurs and tibias of mice. Immunohistology staining, ELISA assay, coimmunoprecipitation, and immunoblot analysis were used to detect the histopathological changes of lung tissues and the expression of inflammatory factors and protein interaction. Results and conclusions: We show a distinct mechanism by which the SARS-CoV-2 N (SARS-2-N) protein targets Bood POZ-containing gene type 2 (BPOZ-2), a scaffold protein for the E3 ubiquitin ligase Cullin 3 that we identified as a negative regulator of inflammatory responses, to promote NLRP3 inflammasome activation. We first demonstrated that BPOZ-2 knockout (BPOZ-2 KO) mice were more susceptible to lipopolysaccharide (LPS)-induced septic shock and ALI and showed increased serum IL-1ß levels. In addition, BMDMs isolated from BPOZ-2 KO mice showed increased IL-1ß production in response to NLRP3 stimuli. Mechanistically, BPOZ-2 interacted with NLRP3 and mediated its degradation by recruiting Cullin 3. In particular, the expression of BPOZ-2 was significantly reduced in lung tissues from mice infected with SARS-CoV-2 and in cells overexpressing SARS-2-N. Importantly, proinflammatory responses triggered by the SARS-2-N were significantly blocked by BPOZ-2 reintroduction. Thus, we concluded that BPOZ-2 is a negative regulator of the NLPR3 inflammasome that likely contributes to SARS-CoV-2-induced hyperinflammation.

Preparation of informative wafers (info-wafers) by combination of 3D printing, code design and photopolymerization.

3D printing is used in manufacturing of personalized and customized medications. Moreover, information technology has been integrated with 3D printing, which builds the basis of informative medications. Here, clonidine hydrochloride (CH) was formulated in informative wafers (info-wafers) by combination of 3D printing, code design and photopolymerization. Braille code (recognized by blind persons), bar code, and quick response (QR) code were used for the design of info-wafers. A code positive mold was 3D-printed with rigid resins by stereolithography, which was transformed to the silicone negative mold by thermal polymerization. A homogeneous CH suspension in N-vinyl pyrrolidone was casted into the negative mold followed by photopolymerization to form CH info-wafers. The bulgy parts of info-wafers were painted with edible ink except for Braille code info-wafers. The CH in info-wafers maintained the amorphous state, which was demonstrated by X-ray diffraction. The amorphous CH had rapid dissolution. Bar code info-wafers were scanned by smartphone though only simple information was obtained. QR code info-wafers were smartphone-scanned to link a website that contained sufficient information such as the instruction of CH application and the collection of patient information. Info-wafers provide online drug information and use instructions for patients to make the treatment standardization and normalization.

Magnetic SERS Strip Based on 4-mercaptophenylboronic Acid-Modified Fe3O4@Au for Active Capture and Simultaneous Detection of Respiratory Bacteria.

The rapid diagnosis and detection of respiratory bacteria at the early stage can effectively control the epidemic spread and bacterial infection. Here, we designed a rapid, ultrasensitive, and quantitative lateral flow immunoassay (LFA) strip for simultaneous detection of respiratory bacteria S. aureus and S. pneumoniae. In this assay, the surface enhanced Raman scattering (SERS) tags were designed through combining magnetite Raman enhancement nanoparticle Fe3O4@Au/DTNB and recognition element 4-mercaptophenylboronic acid (4-MPBA). Further, 4-MPBA could capture multiple bacteria in a complex environmental solution. Based on the strategies, Fe3O4@Au/DTNB-mediated magnetic enrichment and 4-MPBA-mediated universal capture capabilities improved the detection sensitivity, the limits of detection for S. aureus and S. pneumoniae were as low as 8 and 13 CFU mL-1, respectively, which were more sensitive than those of colloidal gold method. The Fe3O4@Au/DTNB/Au/4-MPBA-LFA also exhibited good reproducibility, excellent specificity, and high recovery rates in sputum samples, indicating its potential application in the detection of respiratory bacteria samples.

Predatory bacterial hydrogels for topical treatment of infected wounds.

Wound infection is becoming a considerable healthcare crisis due to the abuse of antibiotics and the substantial production of multidrug-resistant bacteria. Seawater immersion wounds usually become a mortal trouble because of the infection of Vibrio vulnificus. Bdellovibrio bacteriovorus, one kind of natural predatory bacteria, is recognized as a promising biological therapy against intractable bacteria. Here, we prepared a B. bacteriovorus-loaded polyvinyl alcohol/alginate hydrogel for the topical treatment of the seawater immersion wounds infected by V. vulnificus. The B. bacteriovorus-loaded hydrogel (BG) owned highly microporous structures with the mean pore size of 90 µm, improving the rapid release of B. bacteriovorus from BG when contacting the aqueous surroundings. BG showed high biosafety with no L929 cell toxicity or hemolysis. More importantly, BG exhibited excellent in vitro anti-V. vulnificus effect. The highly effective infected wound treatment effect of BG was evaluated on mouse models, revealing significant reduction of local V. vulnificus, accelerated wound contraction, and alleviated inflammation. Besides the high bacterial inhibition of BG, BG remarkably reduced inflammatory response, promoted collagen deposition, neovascularization and re-epithelization, contributing to wound healing. BG is a promising topical biological formulation against infected wounds.

GP73 blockade alleviates abnormal glucose homeostasis in diabetic mice.

Golgi protein 73 (GP73), also called Golgi membrane protein 1 (GOLM1), is a resident Golgi type II transmembrane protein and is considered as a serum marker for the detection of a variety of cancers. A recent work revealed the role of the secreted GP73 in stimulating liver glucose production and systemic glucose homeostasis. Since exaggerated hepatic glucose production plays a key role in the pathogenesis of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), GP73 may thus represent a potential therapeutic target for treating diabetic patients with pathologically elevated levels. Here, in this study, we found that the circulating GP73 levels were significantly elevated in T2DM and positively correlated with hemoglobin A1c. Notably, the aberrantly upregulated GP73 levels were indispensable for the enhanced protein kinase A signaling pathway associated with diabetes. In diet-induced obese mouse model, GP73 siRNA primarily targeting liver tissue was potently effective in alleviating abnormal glucose metabolism. Ablation of GP73 from whole animals also exerted a profound glucose-lowering effect. Importantly, neutralizing circulating GP73 improved glucose metabolism in streptozotocin (STZ) and high-fat diet/STZ-induced diabetic mice. We thus concluded that GP73 was a feasible therapeutic target for the treatment of diabetes.

Plant extracellular vesicles: A novel bioactive nanoparticle for tumor therapy.

Extracellular vesicles are tiny lipid bilayer-enclosed membrane particles, including apoptotic bodies, micro vesicles, and exosomes. Organisms of all life forms can secrete extracellular vesicles into their surrounding environment, which serve as important communication tools between cells and between cells and the environment, and participate in a variety of physiological processes. According to new evidence, plant extracellular vesicles play an important role in the regulation of transboundary molecules with interacting organisms. In addition to carrying signaling molecules (nucleic acids, proteins, metabolic wastes, etc.) to mediate cellular communication, plant cells External vesicles themselves can also function as functional molecules in the cellular microenvironment across cell boundaries. This review introduces the source and extraction of plant extracellular vesicles, and attempts to clarify its anti-tumor mechanism by summarizing the current research on plant extracellular vesicles for disease treatment. We speculate that the continued development of plant extracellular vesicle-based therapeutic and drug delivery platforms will benefit their clinical applications.

Light-triggered on-site rapid formation of antibacterial hydrogel dressings for accelerated healing of infected wounds.

An optimal wound dressing can seal variously shaped wounds and provide a complete barrier to resist bacterial invasion; more importantly, the dressing can be stretched or compressed when the wounds are subjected to external forces and quickly return to its original state after the forces are withdrawn. Here, we designed dressings with light-triggered on-site rapid formation of antibacterial hydrogel for the accelerated healing of infected wounds. The pro-hydrogel, composed of acrylamide (AM) and dopamine-hyaluronic acid-ε-poly-l-lysine (DA-HA-EPL), was filled into the Vibrio vulnificus-infected wound. A 405-nm blue light was exerted on the wound to rapidly photopolymerize AM to its polymer, i.e., polyacrylamide (PAM). A hydrogel network of PAM/DA-HA-EPL immediately formed on site within several seconds to insulate the wound. PAM/DA-HA-EPL possessed adhesion performance to adapt to changes in wound morphologies due to external forces. Moreover, it presented high antibacterial ability due to the presence of EPL, in vitro biocompatibility and the ability to promote cell migration. Vibrio vulnificus-infected wounds were established on full-thickness mouse skin, and the hydrogel dressing exhibited high healing efficiency in terms of skin tissue regeneration, collagen deposition, and angiogenesis. PAM/DA-HA-EPL is a promising hydrogel dressing for the accelerated healing of infected wounds.

Ubiquitin ligase RNF125 targets PD-L1 for ubiquitination and degradation.

As a critical immune checkpoint molecule, PD-L1 is expressed at significantly higher levels in multiple neoplastic tissues compared to normal ones. PD-L1/PD-1 axis is a critical target for tumor immunotherapy, blocking the PD-L1/PD-1 axis is recognized and has achieved unprecedented success in clinical applications. However, the clinical efficacy of therapies targeting the PD-1/PD-L1 pathway remains limited, emphasizing the need for the mechanistic elucidation of PD-1/PD-L1 expression. In this study, we found that RNF125 interacted with PD-L1 and regulated PD-L1 protein expression. Mechanistically, RNF125 promoted K48-linked polyubiquitination of PD-L1 and mediated its degradation. Notably, MC-38 and H22 cell lines with RNF125 knockout, transplanted in C57BL/6 mice, exhibited a higher PD-L1 level and faster tumor growth than their parental cell lines. In contrast, overexpression of RNF125 in MC-38 and H22 cells had the opposite effect, resulting in lower PD-L1 levels and delayed tumor growth compared with parental cell lines. In addition, immunohistochemical analysis of MC-38 tumors with RNF125 overexpression showed significantly increased infiltration of CD4+, CD8+ T cells and macrophages. Consistent with these findings, analyses using The Cancer Genome Atlas (TCGA) public database revealed a positive correlation of RNF125 expression with CD4+, CD8+ T cell and macrophage tumor infiltration. Moreover, RNF125 expression was significantly downregulated in several human cancer tissues, and was negatively correlated with the clinical stage of these tumors, and patients with higher RNF125 expression had better clinical outcomes. Our findings identify a novel mechanism for regulating PD-L1 expression and may provide a new strategy to increase the efficacy of immunotherapy.

GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia.

Severe cases of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with elevated blood glucose levels and metabolic complications. However, the molecular mechanisms for how SARS-CoV-2 infection alters glycometabolic control are incompletely understood. Here, we connect the circulating protein GP73 with enhanced hepatic gluconeogenesis during SARS-CoV-2 infection. We first demonstrate that GP73 secretion is induced in multiple tissues upon fasting and that GP73 stimulates hepatic gluconeogenesis through the cAMP/PKA signaling pathway. We further show that GP73 secretion is increased in cultured cells infected with SARS-CoV-2, after overexpression of SARS-CoV-2 nucleocapsid and spike proteins and in lungs and livers of mice infected with a mouse-adapted SARS-CoV-2 strain. GP73 blockade with an antibody inhibits excessive glucogenesis stimulated by SARS-CoV-2 in vitro and lowers elevated fasting blood glucose levels in infected mice. In patients with COVID-19, plasma GP73 levels are elevated and positively correlate with blood glucose levels. Our data suggest that GP73 is a glucogenic hormone that likely contributes to SARS-CoV-2-induced abnormalities in systemic glucose metabolism.

Antifeedant and Antifungal Activities of Metabolites Isolated from the Coculture of Endophytic Fungus Aspergillus tubingensis S1120 with Red Ginseng.

A new globoscinic acid derivative, aspertubin A (1) along with four known compounds, were obtained from the co-culture of Aspergillus tubingensis S1120 with red ginseng. The chemical structures of compounds were characterized by using spectroscopic methods, the calculated and experimental electronic circular dichroism. Panaxytriol (2) from red ginseng, and asperic acid (4) showed significant antifeedant effect with the antifeedant rates of 75 % and 80 % at the concentrations of 50 µg/cm2 . Monomeric carviolin (3) and asperazine (5) displayed weak attractant activity on silkworm. All compounds were assayed for antifungal activities against phytopathogens A. tubingensis, Nigrospora oryzae and Phoma herbarum and the results indicated that autotoxic aspertubin A (1) and panaxytriol (2) possessed selective inhibition against A. tubingensis with MIC values at 8 µg/mL. The co-culture extract showed higher antifeedant and antifungal activities against P. herbarum than those of monoculture of A. tubingensis in ordinary medium. So the medicinal plant and endophyte showed synergistic effect on the plant disease resistance by active compounds from the coculture of A. tubingensis S1120 and red ginseng.

GP73 is a TBC-domain Rab GTPase-activating protein contributing to the pathogenesis of non-alcoholic fatty liver disease without obesity.

The prevalence of non-obese nonalcoholic fatty liver disease (NAFLD) is increasing worldwide with unclear etiology and pathogenesis. Here, we show GP73, a Golgi protein upregulated in livers from patients with a variety of liver diseases, exhibits Rab GTPase-activating protein (GAP) activity regulating ApoB export. Upon regular-diet feeding, liver-GP73-high mice display non-obese NAFLD phenotype, characterized by reduced body weight, intrahepatic lipid accumulation, and gradual insulin resistance development, none of which can be recapitulated in liver-GAP inactive GP73-high mice. Common and specific gene expression signatures associated with GP73-induced non-obese NAFLD and high-fat diet (HFD)-induced obese NAFLD are revealed. Notably, metformin inactivates the GAP activity of GP73 and alleviates GP73-induced non-obese NAFLD. GP73 is pathologically elevated in NAFLD individuals without obesity, and GP73 blockade improves whole-body metabolism in non-obese NAFLD mouse model. These findings reveal a pathophysiological role of GP73 in triggering non-obese NAFLD and may offer an opportunity for clinical intervention.

The chemical diversity, the attractant, anti-acetylcholinesterase, and antifungal activities of metabolites from biocontrol Trichoderma harzianum uncovered by OSMAC strategy.

Eight new compounds (1-8) were discovered from Trichoderma harzianum associated with edible mushroom by the one strain many compounds (OSMAC) strategy. Triharzianin A (1) is the first naturally scaffold characterized by a C13-prostaglandin skeleton. The configurations of 1-3, and 5 were determined by the Mosher's method, experimental and calculated ECD spectra, and plausible biosynthesis of stereospecific epoxidation. Most compounds indicated obvious feeding attractant activities to silkworm with attraction rates at 30-90%. Compound 7 showed anti-acetylcholinesterase (anti-AChE) activity with a ratio of 29% at a concentration of 50 µM for insecticidal potential. So 2,​3-​dialkylchromone (7) had potential of chemical entrapment and killing of insects. Compounds 2, 3 and 7-11 showed antifungal activities against Aspergillus fumigates, and Trichoderma sp. from mushroom with MICs ≤ 300 µM. The four fermentation extracts also indicated obvious feeding attractant activities to silkworm for the activities brought by active metabolites from T. harzianum. The material base of biocontrol induced by the interaction of host-fungal symbiont can be investigated by the antifungal metabolites against pathogen fungi.

Inhalable Jojoba Oil Dry Nanoemulsion Powders for the Treatment of Lipopolysaccharide- or H2O2-Induced Acute Lung Injury.

Jojoba (Simmondsia chinensis (Link) C.K. Schneid) is a dioecious plant in desert and semi-desert areas, e.g., the Ismailia Desert in Egypt. Jojoba oil (JJBO) is a natural slight yellow oil with the functions of skin barrier repairing and wound healing, which is dermally applied as a traditional medication or cosmetic in the Middle East. The objective of this study was to prepare JJBO dry nanoemulsion powders (JNDs) and investigate their anti-acute lung injury effects. JJBO nanoemulsions (JNEs) were prepared and then lyophilized to JNDs and the properties and simulated lung deposition were measured. Rat acute lung injury (ALI) models were established after intratracheal (i.t.) administration of lipopolysaccharide (LPS) or hydrogen peroxide (H2O2). JNDs and dexamethasone (DXM) solutions were also i.t. administered to the rats. The pathological states of lung tissues were checked. Inflammatory and oxidative factors in the lung tissues were determined using ELISA methods. NF-κB p65 and caspase-3 were measured with a Western blotting method and an immunohistochemical method, respectively. JNDs had an appropriate mass median aerodynamic diameter (MMAD) of 4.17 µm and a fine particle fraction (FPF) of 39.11%. JNDs showed higher anti-inflammatory effect on LPS-induced ALI than DXM with a decrease in total protein content and down-regulation of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and NF-κB p65. JNDs also showed higher anti-inflammatory and anti-oxidation effect on H2O2-induced ALI than DXM with elimination of reactive oxygen species (ROS), increasing of superoxide dismutase (SOD), decrease in of lipid peroxide malondialdehyde (MDA) and glutathione (GSH), and inhibition of caspase-3 expression. Moreover, i.t. JNDs attenuated bleeding and infiltrations of the inflammatory cells in the two ALI models. JNDs are a promising natural oil-contained inhalable medication for the treatment of LPS- or H2O2-induced ALI.

Geochemical Characteristics and the Origin of Superdeep Condensates in Tarim Basin, China.

A series of trace compounds (diamondoids, ethanodiamondoids, and thiadiamondoids) were detected through two-dimensional gas chromatography/time-of-flight mass spectrometry (GC × GC-TOFMS) analysis of Ordovician condensate samples from the Tazhong area. Gas chromatography-mass spectrometry (GC-MS) analysis showed that the biomarker parameters are less effective for high-maturity oils. Carbon isotope and geochemical features suggested that the gas is a high-temperature cracking gas when its temperature is higher than 170 °C. The H2S content is 8.27%, suggesting that it is affected by thermochemical sulfate reduction (TSR). However, the geological analysis indicated that the Ordovician reservoirs do not satisfy the conditions for TSR. The high-maturity oil in the Ordovician reservoirs may generate diamondoids and ethanodiamondoids when cracking, while TSR and severe cracking occur in deep Cambrian source rocks and produce a large number of diamondoids, ethanodiamondoids, organic sulfur compounds (OSCs), etc. The secondary geochemical products that are carried up by the dry gas and migrate upward through faults and are enriched in Ordovician crude oil reservoirs. On this basis, we proposed that the condensate presented was formed by the mixing of dry gas from Cambrian oil that was altered by cracking and TSR into Ordovician in situ slightly cracked oil, therefore speculating that the favorable reservoir-seal assemblages in this area may contain abundant oil and gas resources. Consequently, improved knowledge of secondary alteration effects on the reservoir and underground fluids is vital for oil and gas prediction and exploration development in the next step.

Subjective responses predict d-amphetamine choice in healthy volunteers.

BACKGROUND: It is commonly believed that drugs, including stimulants, are used recreationally because of their ability to induce pleasurable subjective effects. However, recreational drug use sometimes occurs in the absence of positive subjective effects, suggesting that other factors contribute. Here, we examine the extent to which the direct subjective effects of amphetamine, a commonly misused stimulant, predict subsequent choice of the drug vs placebo. METHODS: Healthy adults (N = 112) participated in a five-session amphetamine choice study. On the first four sessions, participants sampled either 20 mg d-amphetamine or placebo in color-coded capsules two times each. On the fifth session, they chose which color (d-amphetamine or placebo) they preferred. We examined the choice of drug vs placebo in relation to demographic characteristics, baseline mood states, personality and subjective and cardiovascular responses to acute administration of the drug. RESULTS: Eighty-one participants chose amphetamine (Choosers) while 31 chose placebo (Non-choosers). Overall, amphetamine produced typical stimulant-like effects on subjective questionnaires, and it elevated heart rate and blood pressure vs placebo. Choosers reported greater positive mood, elation and stimulant-like effects following amphetamine compared to Non-choosers. The Choosers also exhibited a greater increase in systolic blood pressure, but not heart rate. The groups did not differ on demographic characteristics, mood states before drug administration or personality. CONCLUSIONS: These findings support the idea that pleasurable subjective responses to amphetamine, including positive mood, elation, and stimulant-like effects influence behavioral choice of the drug.

Origin and Distribution of Large Asphaltite in South China.

Large quantities of Triassic solid asphaltite were discovered in the Guangyuan area, northwest Sichuan. The asphaltite is formed in layers with a vertical thickness between 0.3 and 2.8 m and is stably distributed with intrusive contact with surrounding rocks. This study aims on the genesis and distribution of asphaltite through trace element, biomarker, and Re-Os isotope analyses. Trace element analysis shows the enrichment of V and Cr in the asphaltite, indicating that it is derived from relatively deep hydrocarbon sources. The carbon isotope and biomarker results suggest that the asphaltite originates from Cambrian paleo reservoir. The Re-Os isotope analysis determines a formation age of 220 ± 6 Ma, which corresponds to the late Triassic, indicating the cracking of paleo reservoirs in late Triassic. Therefore, the origin of asphaltite is epigenetic-reservoir asphaltite. The generation of oil from Cambrian source rocks began at the end of Silurian and ended after Caledonian orogeny. At the end of Permian, the fracture system was well developed due to the influence of the Hercynian movement, which provided favorable conditions for the migration of Cambrian oil. By the end of Triassic, hydrocarbons generated from Cambrian source rocks were mainly distributed in fractures and reservoirs, thus forming paleo oil reservoirs. Afterward, the paleo reservoirs were adjusted to the surface or near the surface during the Indosinian movement and thus have cracked into asphaltite. The distribution of asphaltite is closely related to the tectonic activities, and the asphaltite is preferentially stored in the anticline axes, fissures, and some interlayer fracture zones.

Subjective Effects of Alcohol Predict Alcohol Choice in Social Drinkers.

INTRODUCTION: Alcohol is among the most commonly used psychoactive drugs, yet it can produce markedly different subjective effects in different people. Certain effects, including both heightened stimulatory effects and lesser sedative effects, are thought to predict repeated or excessive use. However, we do not fully understand the nature of these individual differences or their relationships to alcohol consumption. This controlled laboratory study examined subjective and physiologic responses to a moderate dose of alcohol in social drinkers in relation to the subjects' decision to consume alcohol. METHODS: Healthy adult volunteers (N = 95) participated in a 5-session double-blind alcohol choice study. On the first 4 sessions, they received alcohol (0.8 g/kg) and placebo in alternating order, and on the fifth session, they chose and consumed whichever of the 2 they preferred. During each session, participants completed the Profile of Mood States (POMS) and Biphasic Alcohol Effects Scale (BAES) questionnaires and had their vitals recorded every 30 minutes. We compared subjective and physiologic response to alcohol during the sampling sessions in participants who chose alcohol or placebo on session 5. RESULTS: Of the 95 participants, 55 chose alcohol (choosers) and 40 chose placebo (nonchoosers). In the full sample, alcohol produced its expected effects (e.g., increased friendliness, elation, and vigor (POMS), and stimulation and sedation (BAES)). The chooser and nonchooser groups did not differ in demographic characteristics, blood alcohol levels, or cardiovascular measures. However, the choosers experienced greater alcohol-induced increases in positive mood (POMS) and liked the drug more, whereas the nonchoosers experienced greater anger, anxiety (POMS), and sedation (BAES) after alcohol. CONCLUSION: Both greater positive mood effects and lesser sedative effects after alcohol predicted preference under controlled conditions, suggesting that both factors can predict future consumption of alcohol.

Plum-blossom needle for coronavirus disease 2019-related headache: A protocol for systematic review and meta-analysis.

BACKGROUND: Assessing the effectiveness and safety of plum-blossom needle for (COVID-19) related headache is the main purpose of this systematic review protocol. METHODS: We will search the following sources for the identification of trials: The Cochrane Library, PubMed, EMBASE, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure Database (CNKI), Chinese Science and Technique Journals Database (VIP), and the Wanfang Database. The searches were limited to articles published in 2020, but no language restrictions were imposed. Only include randomised controlled trials (RCTs), with or without blinding, and participant or observer reported outcomes, will be included.The primary outcome is the time and rate of appearance of headache induced by COVID-19. The secondary outcome is the length of hospital stay. Two independent reviewers will conduct the study selection, data extraction and assessment. Review Manager Software V.5.3 will be used for the assessment of risk of bias and data synthesis. RESULTS: The results will provide a high-quality synthesis of current evidence for researchers in this subject area. CONCLUSION: The conclusion of our study will provide an evidence to judge whether plum-blossom needle is effective and safe for COVID-19-related headache. ETHICS AND DISSEMINATION: This protocol will not evaluate individual patient information or affect patient rights and therefore does not require ethical approval. Results from this review will be disseminated through peer-reviewed journals and conference reports. PROSPERO REGISTRATION NUMBER: CRD42020199508.