Targeting neutrophil extracellular traps: A novel strategy in hematologic malignancies.

Neutrophil extracellular traps (NETs) have emerged as a critical factor in malignant hematologic disease pathogenesis. These structures, comprising DNA, histones, and cytoplasmic proteins, were initially recognized for their role in immune defense against microbial threats. Growing evidence suggests that NETs contribute to malignant cell progression and dissemination, representing a double-edged sword. However, there is a paucity of reports on its involvement in hematological disorders. A comprehensive understanding of the intricate relationship between malignant cells and NETs is necessary to explore effective therapeutic strategies. This review highlights NET formation and mechanisms underlying disease pathogenesis. Moreover, we discuss recent advancements in targeted inhibitor development for selective NET disruption, empowering precise design and efficacious therapeutic interventions for malignant hematologic diseases.

Association between the systemic immune inflammation index and periodontitis: a cross-sectional study.

BACKGROUND: Periodontitis is a chronic oral inflammatory disease that seriously affects people's quality of life. The purpose of our study was to investigate the correlation between the systemic immune inflammation index (SII) and periodontitis by utilizing a large national survey. This will establish a reference for the early identification and management of periodontitis. METHODS: This study comprised the adult US population who participated in a national periodontitis surveillance project during the six years from 2009 to 2014. Through the utilization of univariate and multivariate weighted logistic regression, we investigated the correlation between the systemic immune inflammation index and periodontitis. Additionally, we employed sensitivity analyses to evaluate the robustness of our findings. RESULTS: The study involved 10,366 participants with an average age of 51.00 years, of whom 49.45% were male (N = 5126) and 50.55% were female (N = 5240). The prevalence of periodontitis is estimated to be about 38.43% in the US adults aged 30 or older population. Our logistic regression models indicated a positive association between a SII higher than 978 × 109/L and periodontitis. The elder group (aged 50 or older) with SII higher than 978 × 109/L demonstrated a significant correlation with periodontitis in the fully adjusted model (Odds Ratio [OR] = 1.409, 95% Confidence Interval [CI] 1.037, 1.915, P = 0.022). However, there is no statistical difference among adults aged 30 to 50. The robustness of our findings was confirmed through sensitivity analyses. CONCLUSIONS: Our study highlights that SII is associated with periodontitis in a nationally representative sample of US adults. And the SII is significantly associated with a high risk of periodontitis in individuals aged 50 or older.

Association between antihypertensive drugs and oral cancer: a drug target Mendelian randomization study.

Background: Recent reports have suggested that antihypertensive drugs may play an oncogenic role in common cancers, but it is still uncertain whether this could influence the risk of oral cancer. Through two-sample Mendelian randomization (MR), we sought to assess the causal effect of antihypertensive drugs on oral cancer outcomes. Methods: To proxy the exposure of antihypertensive drugs, we utilized two genetic instruments, including expression quantitative trait loci of drug target genes and genetic variants within or around drug target genes related to blood pressure from genome-wide association studies. Inverse-variance-weighted MR (IVW-MR) and summary-data-based MR (SMR) were employed to compute the instrument effect estimates. Results: It was observed through IVW-MR analysis that there is a positive relationship between KCNH2 (target of beta-adrenoceptor blockers)-mediated blood pressure and oral cancer (odds ratio [OR] = 1.197, 95% confidence interval [CI] = 1.028-1.394). Similarly, SMR analysis demonstrated that a higher expression of KCNH2 (target of beta-adrenoceptor blockers) was linked to a greater risk of oral cancer (OR = 2.223, 95% CI = 1.094-4.516). Both analyses yielded no consistent evidence of other associations. Conclusion: This two-sample MR study proposed a latent causal association between KCNH2 (target of beta-adrenoceptor blockers) inhibition and diminished risk of oral cancer.

Effectiveness and safety of camrelizumab-containing neoadjuvant therapy in patients with esophageal squamous cell carcinoma: a prospective multicenter observational cohort study.

Background: Camrelizumab has been demonstrated to be a feasible treatment option for locally advanced esophageal squamous cell carcinoma (ESCC) when combined with neoadjuvant chemotherapy. This trial was conducted to investigate the effectiveness and safety of camrelizumab-containing neoadjuvant therapy in patients with ESCC in daily practice. Methods: This prospective multicenter observational cohort study was conducted at 13 tertiary hospitals in Southeast China. Patients with histologically or cytologically confirmed ESCC [clinical tumor-node-metastasis (cTNM) stage I-IVA] who had received at least one dose of camrelizumab-containing neoadjuvant therapy were eligible for inclusion. Results: Between June 1, 2020 and July 13, 2022, 255 patients were enrolled and included. The median age was 64 (range, 27 to 82) years. Most participants were male (82.0%) and had clinical stage III-IVA diseases (82.4%). A total of 169 (66.3%) participants underwent surgical resection; 146 (86.4%) achieved R0 resection, and 36 (21.3%) achieved pathological complete response (pCR). Grades 3-5 adverse events (AEs) were experienced by 14.5% of participants. Reactive cutaneous capillary endothelial proliferation occurred in 100 (39.2%) of participants and all were grade 1 or 2. Conclusions: Camrelizumab-containing neoadjuvant therapy has acceptable effectiveness and safety profiles in real-life ESCC patients.

The efficacy and safety of thermal ablation for patients with lung malignancy: a meta-analysis of 12 studies in China.

BACKGROUND: Thermal ablation has been increasingly used in the treatment of lung cancer in recent years. This meta-analysis aims to investigate the therapeutic effect and safety of thermal ablation plus chemotherapy as compared with chemotherapy alone in treating patients with lung malignancy in China based on current evidence. METHODS: Databases including PubMed, Web of Science, Embase and the Cochrane Library were searched for clinical reports. Additional literature search was also performed by searching the reference list of included studies and latest reviews. Raw data including objective response rate, disease control rate, progression-free survival, overall survival and the incidence of major complication were extracted and pooled. RESULTS: A total of 12 studies in China including 1282 patients with lung malignancy were included in this meta-analysis. The number of studies that reported data of objective response rate, disease control rate, progression-free survival, overall survival and major complication was 8, 7, 7, 6 and 7, respectively. The combination therapy of thermal ablation plus chemotherapy showed a significantly better efficacy in improving objective response rate (odds ratio = 2.73; P < 0.001) and disease control rate (odds ratio = 2.43; P < 0.001) as compared with chemotherapy alone. Thermal ablation was also a significant protective factor for progression-free survival (hazard ratio = 0.43; P < 0.001) and overall survival (hazard ratio = 0.49; P < 0.001). Besides, thermal ablation did not increase the risk of major complication (odds ratio = 0.75; P = 0.252). CONCLUSION: The present meta-analysis based on these studies in China suggested that thermal ablation is a promising technique to provide better disease response and survival outcomes for patients with lung malignancy. Thermal ablation is worth further promotion in treating lung malignancy and application in clinical practice.

Cisplatin causes covalent inhibition of protein-tyrosine phosphatase 1B (PTP1B) through reaction with its active site cysteine: Molecular, cellular and in vivo mice studies.

Protein tyrosine phosphatase 1B (PTP1B) is a critical regulator of different signalling cascades such as the EGFR pathway. The biological importance of PTP1B is further evidenced by knockout mice studies and the identification of recurrent mutations/deletions in PTP1B linked to metabolic and oncogenic alterations. Cisplatin is among the most widely used anticancer drug. The biological effects of cisplatin are thought to arise primarily from DNA damaging events involving cisplatin-DNA adducts. However, increasing evidence indicate that the biological properties of cisplatin could also rely on the perturbation of other processes such as cell signalling through direct interaction with certain cysteine residues in proteins. Here, we provide molecular, cellular and in vivo evidence suggesting that PTP1B is a target of cisplatin. Mechanistic studies indicate that cisplatin inhibited PTP1B in an irreversible manner and binds covalently to the catalytic cysteine residue of the enzyme. Accordingly, experiments conducted in cells and mice exposed to cisplatin showed inhibition of endogenous PTP1B and concomitant increase in tyrosine phosphorylation of EGFR. These findings are consistent with previous studies showing tyrosine phosphorylation-dependent activation of the EGFR pathway by cisplatin and with recent studies suggesting PTP1B inhibition by cisplatin and other platinum complexes. Importantly, our work provides novel mechanistic evidence that PTP1B is a protein target of cisplatin and is inhibited by this drug at molecular, cellular and in vivo levels. In addition, our work may contribute to the understanding of the pathways undergoing modulation upon cisplatin administration beyond of the established genotoxic effect of cisplatin.

Human Protein Tyrosine Phosphatase 1B (PTP1B): From Structure to Clinical Inhibitor Perspectives.

Phosphorylation is an essential process in biological events and is considered critical for biological functions. In tissues, protein phosphorylation mainly occurs on tyrosine (Tyr), serine (Ser) and threonine (Thr) residues. The balance between phosphorylation and dephosphorylation is under the control of two super enzyme families, protein kinases (PKs) and protein phosphatases (PPs), respectively. Although there are many selective and effective drugs targeting phosphokinases, developing drugs targeting phosphatases is challenging. PTP1B, one of the most central protein tyrosine phosphatases (PTPs), is a key player in several human diseases and disorders, such as diabetes, obesity, and hematopoietic malignancies, through modulation of different signaling pathways. However, due to high conservation among PTPs, most PTP1B inhibitors lack specificity, raising the need to develop new strategies targeting this enzyme. In this mini-review, we summarize three classes of PTP1B inhibitors with different mechanisms: (1) targeting multiple aryl-phosphorylation sites including the catalytic site of PTP1B; (2) targeting allosteric sites of PTP1B; (3) targeting specific mRNA sequence of PTP1B. All three types of PTP1B inhibitors present good specificity over other PTPs and are promising for the development of efficient small molecules targeting this enzyme.

Biochemical, Enzymatic, and Computational Characterization of Recurrent Somatic Mutations of the Human Protein Tyrosine Phosphatase PTP1B in Primary Mediastinal B Cell Lymphoma.

Human protein tyrosine phosphatase 1B (PTP1B) is a ubiquitous non-receptor tyrosine phosphatase that serves as a major negative regulator of tyrosine phosphorylation cascades of metabolic and oncogenic importance such as the insulin, epidermal growth factor receptor (EGFR), and JAK/STAT pathways. Increasing evidence point to a key role of PTP1B-dependent signaling in cancer. Interestingly, genetic defects in PTP1B have been found in different human malignancies. Notably, recurrent somatic mutations and splice variants of PTP1B were identified in human B cell and Hodgkin lymphomas. In this work, we analyzed the molecular and functional levels of three PTP1B mutations identified in primary mediastinal B cell lymphoma (PMBCL) patients and located in the WPD-loop (V184D), P-loop (R221G), and Q-loop (G259V). Using biochemical, enzymatic, and molecular dynamics approaches, we show that these mutations lead to PTP1B mutants with extremely low intrinsic tyrosine phosphatase activity that display alterations in overall protein stability and in the flexibility of the active site loops of the enzyme. This is in agreement with the key role of the active site loop regions, which are preorganized to interact with the substrate and to enable catalysis. Our study provides molecular and enzymatic evidence for the loss of protein tyrosine phosphatase activity of PTP1B active-site loop mutants identified in human lymphoma.

Structural characterization of a pathogenic mutant of human protein tyrosine phosphatase PTPN2 (Cys216Gly) that causes very early onset autoimmune enteropathy.

PTPN2 is an important protein tyrosine phosphatase (PTP) that plays a key role in cell signaling. Deletions or inactivating mutations of PTPN2 have been described in different pathologies and underline its critical role in hematopoiesis, autoimmunity, and inflammation. Surprisingly, despite the major pathophysiological implications of PTPN2, the structural analysis of this PTP and notably of its pathogenic mutants remains poorly documented. Contrary to other human PTP enzymes, to date, only one structure of PTPN2 (wild-type form) has been reported. Here, we report the first crystal structure of a pathogenic mutant of PTPN2 (Cys216Gly) that causes an autoimmune enteropathy. We show in particular that this mutant adopts a classical PTP fold. More importantly, albeit inactive, the mutant retains its ability to bind substrates and to adopt the characteristic catalytically competent closed form of PTP enzymes. This novel PTPN2 structure may serve as a new tool to better understand PTP structures and the structural impacts of pathogenic mutations. Moreover, the C216G PTPN2 structure could also be helpful to design specific ligands/inhibitors.

Human CREBBP acetyltransferase is impaired by etoposide quinone, an oxidative and leukemogenic metabolite of the anticancer drug etoposide through modification of redox-sensitive zinc-finger cysteine residues.

Etoposide is an extensively prescribed anticancer drug that, unfortunately, causes therapy-related leukemia. The mechanisms by which etoposide induces secondary hematopoietic malignancies are poorly documented. However, etoposide-related leukemogenesis is known to depend on oxidative metabolites of etoposide, notably etoposide quinone, that can react with protein cysteine residues such as in topoisomerases II. CREBBP is a major histone acetyltransferase that functions mainly as a transcriptional co-activator. This epigenetic enzyme is considered as a tumor suppressor that plays a major role in hematopoiesis. Genetic alterations affecting CREBBP activity are highly common in hematopoietic malignancies. We report here that CREBBP is impaired by etoposide quinone. Molecular and kinetic analyses show that this inhibition occurs through the rapid and covalent (kinhib = 16.102 M-1. s-1) adduction of etoposide quinone with redox sensitive cysteine residues within the RING and PHD Zn2+-fingers of CREBBP catalytic core leading to subsequent release of Zn2+. In agreement with these findings, experiments conducted in cells and in mice treated with etoposide showed irreversible inhibition of endogenous CREBBP activity and decreased H3K18 and H3K27 acetylation. As shown for topoisomerases II, our work thus suggests that the leukemogenic metabolite etoposide quinone can impair the epigenetic CREBBP acetyltransferase through reaction with redox sensitive cysteine residues.

From transglutaminases (TGs) to arylamine N-acetyltransferases (NATs): Insight into the role of a spatially conserved aromatic amino acid position in the active site of these two families of enzymes.

Transglutaminases (TG) and arylamine N-acetyltransferases (NAT) are important family of enzymes. Although they catalyze different reactions and have distinct structures, these two families of enzymes share a spatially conserved catalytic triad (Cys, His, Asp residues). In active TGs, a conserved Trp residue located close to the triad cysteine is crucial for catalysis through stabilization of transition states. Here, we show that in addition to sharing a similar catalytic triad with TGs, functional NAT enzymes also possess in their active site an aromatic residue (Phe, Tyr or Trp) occupying a structural position similar to the Trp residue of active TGs. More importantly, as observed in active TGs, our data indicates that in functional NAT enzymes this conserved aromatic residue is also involved in stabilization of transition states. These results thus indicate that in addition to the three triad residues, these two families of enzymes also share a spatially conserved aromatic amino acid position important for catalysis. Identification of residues involved in the stabilization of transition states is important to develop potent inhibitors. Interestingly, NAT enzymes have been shown as potential targets of clinical interest.

TNBG-5602, a novel derivative of quinoxaline, inhibits liver cancer growth via upregulating peroxisome proliferator-activated receptor γ in vitro and in vivo.

OBJECTIVES: TNBG-5602 is a newly synthesized compound with an isoquinoline structure. In the present study, we demonstrated the anticancer effect of TNBG-5602 in in-vitro and in-vivo models and investigated its possible anticancer mechanism. METHODS: The antiproliferation effect of TNBG-5602 in vitro was evaluated in human liver cancer cell line QGY-7701. The acute toxicity of TNBG-5602 was evaluated in mice. The anticancer activity of TNBG-5602 in vivo was assessed in a xenograft model of human liver cancer cell line QGY-7701. KEY FINDINGS: The results of CCK-8 assay showed that TNBG-5602 can effectively inhibit the proliferation of liver cancer cells in vitro. The acute toxicity test in mice showed that the LD50 of TNBG-5602 was 172 mg/kg. In a xenograft liver cancer model, TNBG-5602 could remarkably inhibit the growth of tumours. During in-vitro and in-vivo studies, we noted that TNBG-5602 could induce lipid accumulation in cancer cells and tissues. Further study indicated that the anticancer effect of TNBG-5602 may be exerted through activating peroxisome proliferator-activated receptor γ (PPARγ) and downregulating proliferating cell nuclear antigen (PCNA). CONCLUSIONS: Our results suggested that TNBG-5602 might exert potent anticancer activity through increasing the expression of PPARγ.

T-Cell Protein Tyrosine Phosphatase Is Irreversibly Inhibited by Etoposide-Quinone, a Reactive Metabolite of the Chemotherapy Drug Etoposide.

Etoposide is a widely prescribed anticancer drug that is, however, associated with an increased risk of secondary leukemia. Although the molecular basis underlying the development of these leukemias remains poorly understood, increasing evidence implicates the interaction of etoposide metabolites [i.e., etoposide quinone (EQ)] with topoisomerase II enzymes. However, effects of etoposide quinone on other cellular targets could also be at play. We investigated whether T-cell protein tyrosine phosphatase (TCPTP), a protein tyrosine phosphatase that plays a key role in normal and malignant hematopoiesis through regulation of Janus kinase/signal transducer and activator of transcription signaling, could be a target of EQ. We report here that EQ is an irreversible inhibitor of TCPTP phosphatase (IC50 = ∼7 µM, second-order rate inhibition constant of ∼810 M-1⋅min-1). No inhibition was observed with the parent drug. The inhibition by EQ was found to be due to the formation of a covalent adduct at the catalytic cysteine residue in the active site of TCPTP. Exposure of human hematopoietic cells (HL60 and Jurkat) to EQ led to inhibition of endogenous TCPTP and concomitant increase in STAT1 tyrosine phosphorylation. Our results suggest that in addition to alteration of topoisomerase II functions, EQ could also contribute to etoposide-dependent leukemogenesis through impairment of key hematopoietic signaling enzymes, such as TCPTP.

Anticancer effects of oridonin on colon cancer are mediated via BMP7/p38 MAPK/p53 signaling.

Colon cancer is a prevalent malignancy affecting the gastrointestinal tract. Oridonin (ORI) is a promising chemotherapeutic drug used in the treatment of colon cancer. In this study, we examined the anticancer activity of ORI against colon cancer and elucidated the underlying molecular mechanisms. Cell counting kit-8, flow cytometric and western blot analyses were conducted to analyze the growth inhibitory effects of ORI on SW620 cells; we employed BMP7 and p53 recombinant adenovirus to detect the influence of ORI on the p38 MAPK signal pathway; PT-qPCR, cell immunofluorescence staining and western blot analysis were used to detect the expression of BMP7, p38 and p-p38, p53 and p-p53. A xenograft tumor model and histological evaluation were introduced to detect the effects of ORI and BMP7 in SW620 cells in vivo. ORI inhibited the proliferation of SW620 cells and induced apoptosis. ORI also increased the total and phosphorylated levels of p53. The overexpression of p53 was found to enhance the anti-proliferative effects of ORI on the SW620 cells, while the inhibition of p53 partially reversed these effects. ORI increased the expression of bone morphogenetic protein 7 (BMP7) in the SW620 cells. The overexpression of BMP7 also enhanced the antiproliferative effects of ORI on the SW620 cells and reduced the growth rate of tumors in mice. BMP7-induced immunosuppression markedly decreased the anti-proliferative effects of ORI. ORI was not found to exert any substantial effect on the phosphorylation levels of Smad1/5/8, although it increased the level of p-p38 significantly. The inhibition of p38 significantly attenuated the ORI-induced increase in the levels of p-p53. The overexpression of BMP7 enhanced the promoting effects of ORI on the p-p53 and p-p38 levels, while BMP7-induced immunosuppression reduced the effects of ORI on p-p38 and p-p53. On the whole, the findings of this study suggest that ORI may be a promising agent for use in the treatment of colon cancer, and the anticancer effects of ORI may be partially mediated through the BMP7/p38 MAPK/p53 signaling pathway.

Pioglitazone/metformin adduct regulates insulin secretion and inhibits high glucose-induced apoptosis via p21-p53-MDM2 signaling in INS-1 cells.

Pioglitazone/metformin adduct is a novel compound synthesized from pioglitazone and metformin combined at a molar mass ratio of 1:1. The aim of this study was to investigate the effects of pioglitazone/metformin adduct on high glucose-induced insulin secretion and apoptosis in INS-1 cells. Western blot and CCK8 analyses showed that the death rate of INS-1 cells increased in response to glucose treatment in a concentration-dependent manner. ELISA assays and Western blot analyses showed that insulin secretion peaked following treatment with glucose concentration at 33.33 mM. Treatment of INS-1 cells with 1 µM pioglitazone/metformin adduct in the presence of 33.33 mM glucose greatly improveded the levels of insulin and apoptosis rates compared to those of the control group. Analysis of mechanism underlying these effects revealed the involvement of the p21-p53-MDM2 signaling pathway. Our results indicate that pioglitazone/metformin adduct is superior to pioglitazone and/or metformin in regulating high glucose-induced insulin secretion and apoptosis in INS-1 cells.

BMP7 mediates the anticancer effect of honokiol by upregulating p53 in HCT116 cells.

Colorectal cancer (CRC) is the second leading cause of cancer death. Hence, there is a great need to explore new efficacious drugs for the treatment of CRC. Honokiol (HNK), a natural product extracted from magnolia bark, processes various biological activities, including anticancer. In this study, we introduced cell viability assay, western blotting, real-time PCR and immunofluorescent staining to determine the anticancer effect of HNK, and the possible mechanism underlying this biological process. We found that HNK can inhibit the proliferation and induce apoptosis in HCT116 cells in a concentration- and time-dependent manner. HNK activates p53 in HCT116 and other colon cancer cells. Exogenous p53 potentiates the anticancer of HNK, while p53 inhibitor decreases this effect of HNK. Moreover, HNK upregulates the expression of bone morphogenetic protein 7 (BMP7) in colon cancer cells; Exogenous BMP7 enhances the anticancer activity of HNK and BMP7 specific antibody reduces this effect of HNK. For mechanism, we found that HNK cannot increase the level of Smad1/5/8; Exogenous BMP7 potentiates the HNK-induced activation of p53. On the contrary, BMP7 specific antibody inhibits the HNK-induced activation of p53 in colon cancer cells and partly decreases the total level of p53. Our findings suggested that HNK may be a promising anticancer drug for CRC; activation of p53 plays an important role in the anticancer activity of HNK, which may be initialized partly by the HNK-induced upregulation of BMP7.

TGF-ß1/PTEN/PI3K signaling plays a critical role in the anti-proliferation effect of tetrandrine in human colon cancer cells.

The diagnosis and treatment for colon cancer have been greatly developed, but the prognosis remains unsatisfactory. There is still a great clinical need to explore new efficacious drugs for colon cancer treatment. Tetrandrine (Tet) is a bis-benzylisoquinoline alkaloid. It has been shown that Tet may be a potential candidate for cancer treatment, but the explicit mechanism underlying this activity remains unclear. In this study, we investigated the anticancer activity of Tet in human colon cancer cells and dissected the possible mechanism. With cell viability assay and flow cytometry analysis, we confirmed that Tet can effectively inhibit the proliferation and induce apoptosis in HCT116 cells. Mechanically, we found that Tet greatly increases the mRNA and protein level of TGF-ß1 in HCT116 cells. Exogenous TGF-ß1 enhances the anti-proliferation and apoptosis inducing effect of Tet in HCT116 cells, which has been partly reversed by TGF-ß1 inhibitor. Tet decreases the phosphorylation of Akt1/2/3 in HCT116 cells. This effect can be enhanced by exogenous TGF-ß1, but partly reversed by TGF-ß1 inhibitor. Tet exhibits no effect on total level of PTEN, but decreases the phosphorylation of PTEN; exogenous TGF-ß1 enhances the effect of Tet on decreasing the phosphorylation of PTEN, which was partly reversed by TGF-ß1 inhibitor. Our findings suggested that Tet may be a promising candidate for colon cancer treatment, and the anticancer activity may be mediated by inactivating PI3K/Akt signaling through upregulating TGF-ß1 to decrease the phosphorylation of PTEN.

[A new species of Culicoides (Beltranmyia) from China (Diptera:Ceratopogonidae)].

OBJECTIVE: To investigate the species of blood-sucking midges of Shanghai. METHODS: The specimens were collected by light-trap from Pudong Airport (reed marshes), Shanghai, during the years of 2007-2009. The captured samples was briefly classified, and mounted slide specimens with phenol-balsam method. The microscopic examination including morphological and numerical characters for species identification. RESULTS: A new species of biting midges named Culicoides (Beltranmyia) shanghaiensis sp. nov. was obtained, its diagnostic characters were as follows: 1) wing without distinct pale or dark markings, only 0-7 macrotrichia find in basal cell; 2) the female eyes separate, with pubescence between facets, proboscis head ratio (P/H) 0.7, while the head proboscis ratio (H/P) 1.45, antennal ratio (AR) 1.18, sensila coeloconica present on segments 3-14 (frequency: 1.0, 0.7, 0.5, 0.5, 0.7, 0.5, 0.8, 0.7, 1.0, 1.0, 1.0, 1.0, respectively, n = 17) and absent on segments 4-10 indefinitely, with one developed spermatheca; 3) the male's parameres fused narrowly on base. The new species is allied to Culicoides homochrous Remm, but can be distinguished chiefly by: its wing with numerous macrotrichias distributing in basal cell; female eyes separate, bare, H/P 1.03-1.04; male's parameres separate. Besides, the Culicoides charadraeus Arnaud and Culicoides rarus Das Gupta also resembling with the new species, it can be differentiated from the two former species by the female eyes bare and contiguous (or narrowly separated), AR > 1.61, no macrotrichia in basal cell of the wings, and the different male genitalia features. CONCLUSION: A new species of biting midges collected from Shanghai is described, and some diagnostic characters are discussed for distinguishing the closely allied species.