Recent Advances in Halogen-Metal Exchange Reactions.

ConspectusThe halogen-metal exchange reaction is a very powerful method for preparing functionalized organometallic reagents in the fields of organic and organometallic chemistry. Since its inception, significant interest has been directed toward the on-demand development of new halogen-metal exchange reactions, primarily through the upgrading of exchange reagents. The enduring quest for optimal reactivity, superior functional group compatibility, and innovative synthetic applications of exchange reagents remains a fundamental objective. In the past several years, the emergence of some significant discoveries in halogen-metal exchange reactions has proclaimed a renaissance to this field. This Account outlines the latest advances within the domain contributed by the Knochel group, including the main points as follows.The stereoretentive I/Li exchange on stereodefined secondary alkyl iodides was developed for the synthesis of nonstabilized chiral secondary alkyllithium reagents. This provided a straightforward method to access chiral organolithium reagents, which can be trapped by various electrophiles or transmetalated with other metals such as copper, zinc, and magnesium, thus enabling the stereoselective synthesis of a series of functionalized compounds and natural products.Faster halogen-magnesium and halogen-zinc exchanges in toluene were realized using a novel kind of exchange reagent complexed with lithium alkoxide. These highly efficient exchange reactions are much faster than traditional ones and performed in an industrially friendly solvent. These advantages are of great value in practical synthesis, paving the way for new developments in this evolving area.Halogen-lanthanide exchanges and their novel applications in organic synthesis were established. These new exchanges introduced the lanthanide metals into halogen-metal exchange reactions for the first time, thereby opening new avenues in synthetic chemistry. Building on these achievements, a comparative analysis of the exchange reaction rates by kinetic study has quantified the relationship between the electronegativity of metals and the rates of halogen-metal exchanges.Br/Na exchange in continuous flow was achieved using a hexane-soluble exchange reagent, 2-ethylhexylsodium. This approach effectively circumvented the poor solubility of the organosodium reagent, which has proven to be of significant practical value and greatly enhanced the synthetic utility of the organosodium reagent in organic synthesis.These remarkable breakthroughs as mentioned above are fueled mainly by upgrading the exchange reagents, resulting in the development of new halogen-metal exchange reactions and innovative applications in organic synthesis. Given the importance of halogen-metal exchanges in synthetic chemistry, the pursuit of other types of exchange reactions, particularly those involving new metals, will be in continuous demand. This Account provides a timely summary of recent progress and will undoubtedly inspire further advances to drive this research field forward.

In Situ X-Ray Techniques Unraveling Charge Distribution Induced by Halogen Bonds in Solvates of an Iodo-Substituted Squaraine Dye.

The importance of halogen bonds (XBs) in the regulation of material properties through a variation in the electrostatic potential of the halogen atom is not attracted much attention. Herein, this study utilizes in situ single crystal X-ray diffraction and synchrotron-based X-ray techniques to investigate the cooling-triggered irreversible single-crystal-to-single-crystal transformation of the DMF solvated iodo-substituted squaraine dye (SQD-I). Transformation is observed to be mediated by solvent-involved XB formation and strengthening of electrostatic interaction between adjacent SQD-I molecules. By immersing a DMF solvate in acetonitrile a solvent exchange without loss of long-range ordering is observed. This is attributed to conservation of the molecular charge distribution of SQD-I molecules during the process. The different solvates can be used in combination for temperature-dependent image encryption. This work emphasizes the changes caused by XB formation to the electrostatic potentials of halogen containing molecules and their influence on material properties and presents the potential utility of XBs in the design of soft-porous crystals and luminescent materials.

Association of higher transient receptor potential melastatin 8 expression with higher tumor histologic grades, lymph node metastasis, risk factors, and worse survival in patients with head and neck squamous cell carcinoma.

Background/purpose: Transient receptor potential melastatin 8 (TRPM8), a thermosensitive ion channel known for its role in cold sensation and menthol response, has emerged as a potential regulator in various cancers. This study aimed to investigate expression trends of TRPM8 in head and neck squamous cell carcinoma (HNSCC) cases and oral squamous cell carcinoma (OSCC) cell lines and its association with clinicopathological features. Materials and methods: The noncancerous matched tissues and HNSCC paired tissue samples from 84 HNSCC patients were utilized to evaluate the association of TRPM8 with HNSCC clinicopathological features. TRPM8 expression was examined in HNSCC patient tissues and OSCC cell lines treated with arecoline. Results: Kaplan-Meier survival analysis of TCGA data revealed high TRPM8 expression correlated with unfavorable outcomes and higher tumor histologic grades. TRPM8 mRNA expression was upregulated in HNSCC cell lines and patients' tissue samples. Arecoline treatment led to significantly increased TRPM8 mRNA and protein expression in OSCC cell lines. Lymph node metastasis showed a significant association with upregulated TRPM8 expression in combined OSCC and oropharyngeal squamous cell carcinoma (OPSCC) cases. TRPM8 mRNA expression was upregulated in HNSCC and OSCC patients with alcohol drinking and cigarette smoking habits, but not in betel quid chewing. Conclusion: These findings reveal the involvement of TRPM8 in HNSCC's malignant development and metastasis, suggesting that high expression of TRMP8 may be mutually causal with addiction to tobacco, alcohol, and betel nut in HNSCC patients. Further investigations are needed to determine the underlying pathways of TRPM8 in HNSCC's development and progression.

The Role of Base in Reaction Performance of Photochemical Synthesis of Thiazoles: An Integrated Theoretical and Experimental Study.

Artificial intelligence (AI)/machine learning (ML) is emerging as pivotal in synthetic chemistry, offering revolutionary potential in retrosynthetic analysis, reaction conditions and reaction prediction. We have combined chemical descriptors, primarily based on Density Functional Theory (DFT) calculations, with various AI/ML tools such as Multi-Layer Perceptron (MLP) and Random Forest (RF), to predict the synthesis of 2-arylbenzothiazole in photoredox reactions. Significantly, our models underscore the critical role of the molecular structure and physicochemical characteristics of the base, especially the total atomic polarizabilities, in the rate-determining steps involving cyclohexyl and phenethyl moieties of the substrate. Moreover, we validated our findings in articles through experimental studies. It showcases the power of AI/ML and quantum chemistry in shaping the future of organic chemistry.

Preparation of Aromatic and Heterocyclic Amines by the Electrophilic Amination of Functionalized Diorganozincs with Polyfunctional O-2,6-Dichlorobenzoyl Hydroxylamines.

We report a catalyst-free electrophilic amination, which enables the synthesis of aromatic and heterocyclic amines. By subjecting diarylzinc or diheteroarylzinc compounds to readily accessible O-2,6-dichlorobenzoyl hydroxylamines in the presence of MgCl2 in dioxane at a temperature of 60 °C (8-16 h). This new electrophilic amination allowed an expedited synthesis of two pharmaceutically significant compounds: vortioxetine is a key intermediate of delamanid. This approach offers opportunities for the streamlined synthesis of amine-based molecules in the pharmaceutical industry.

NOx removal and copper recovery from the leaching process for waste printed circuit boards: performance evaluation and potential environmental impact assessment.

Resource recovery is crucial for small- and medium-sized enterprises to attain a circular economy. The economic benefits of recovering precious metals from electronic waste, such as waste printed circuit boards (WPCBs), are hindered by secondary pollutant emissions from pretreatment processes. This study aims to recover copper from the WPCB acid leaching process and reduce NOx emissions through the use of a high gravity rotating packed bed (RPB). The results indicate that the copper recovery ratio increases to 99.75% through the displacement reaction between iron powder and copper nitrate. The kinetic analysis of copper dissolution was employed to simulate the NOx emissions during acid leaching, with an R-squared value of 0.872. Three oxidants, including H2O2(aq), ClO2(aq), and O3(g), with pH adjusted to different NaOH concentrations, were used to remove NOx. The greatest NOx removal rate was achieved using a 0.06 M NaOH solution, with a removal rate of 91.2% for ozone oxidation at a 152-fold gravity level and a gas-to-liquid (G/L) ratio of 0.83. The gas-side mass transfer coefficients (KGa) for NOx range from 0.003 to 0.012 1/s and are comparable to previous studies. The results of a life cycle analysis indicate that the NOx removal rate, nitric acid recycling rate, and copper recovery rate are 85%, 80%, and 100%, respectively, reducing the environmental impact on the ecosystem, human health, and resource depletion by 10% compared to a scenario with no NOx removal.

Electrochemical flow aziridination of unactivated alkenes.

Aziridines derived from bioactive molecules may have unique pharmacological activities, making them useful in pharmacology (e.g. mitomycin C). Furthermore, the substitution of the epoxide moiety in epothilone B with aziridine, an analog of epoxides, yielded a pronounced enhancement in its anticancer efficacy. Thus, there is interest in developing novel synthetic technologies to produce aziridines from bioactive molecules. However, known methods usually require metal catalysts, stoichiometric oxidants and/or pre-functionalized amination reagents, causing difficulty in application. A practical approach without a metal catalyst and extra-oxidant for the aziridination of bioactive molecules is in demand, yet challenging. Herein, we report an electro-oxidative flow protocol that accomplishes an oxidant-free aziridination of natural products. This process is achieved by an oxidative sulfonamide/alkene cross-coupling, in which sulfonamide and alkene undergo simultaneous oxidation or alkene is oxidized preferentially. Further anticancer treatments in cell lines have demonstrated the pharmacological activities of these aziridines, supporting the potential of this method for drug discovery.

Electroacupuncture exerts prolonged analgesic and neuroprotective effects in a persistent dental pain model induced by multiple dental pulp injuries: GABAergic interneurons-astrocytes interaction.

Pain within the trigeminal system, particularly dental pain, is poorly understood. This study aimed to determine whether single or multiple dental pulp injuries induce persistent pain, its association with trigeminal central nociceptive pathways and whether electroacupuncture (EA) provides prolonged analgesic and neuroprotective effects in a persistent dental pain model. Models of single dental pulp injury (SDPI) and multiple dental pulp injuries (MDPI) were used to induce trigeminal neuropathic pain. The signs of dental pain-related behavior were assessed using the mechanical head withdrawal threshold (HWT). Immunofluorescence and western blot protocols were used to monitor astrocyte activation, changes in apoptosis-related proteins, and GABAergic interneuron plasticity. SDPI mice exhibited an initial marked decrease in HWT from days one to 14, followed by progressive recovery from days 21 to 42. From days 49 to 70, the HWT increased and returned to the control values. In contrast, MDPI mice showed a persistent decrease in HWT from days one to 70. MDPI increased glial fibrillary acidic protein (GFAP) and decreased glutamine synthetase (GS) and glutamate transporter-1 (GLT1) expression in the Vi/Vc transition zone of the brainstem on day 70, whereas no changes in astrocytic markers were observed on day 70 after SDPI. Increased expression of cleaved cysteine-aspartic protease-3 (cleaved caspase-3) and Bcl-2-associated X protein (Bax), along with decreased B-cell lymphoma/leukemia 2 (Bcl-2), were observed at day 70 after MDPI but not after SDPI. The downregulation of glutamic acid decarboxylase (GAD65) expression was observed on day 70 only after MDPI. The effects of MDPI-induced lower HWT from days one to 70 were attenuated by 12 sessions of EA treatment (days one to 21 after MDPI). Changes in astrocytic GFAP, GS, and GLT-1, along with cleaved caspase-3, Bax, Bcl-2, and GAD65 expression observed 70 days after MDPI, were reversed by EA treatment. The results suggest that persistent dental pain in mice was induced by MDPI but not by SDPI. This effect was associated with trigeminal GABAergic interneuron plasticity along with morphological and functional changes in astrocytes. EA exerts prolonged analgesic and neuroprotective effects that might be associated with the modulation of neuron-glia crosstalk mechanisms.

SRCAP mutations drive clonal hematopoiesis through epigenetic and DNA repair dysregulation.

Somatic mutations accumulate in all cells with age and can confer a selective advantage, leading to clonal expansion over time. In hematopoietic cells, mutations in a subset of genes regulating DNA repair or epigenetics frequently lead to clonal hematopoiesis (CH). Here, we describe the context and mechanisms that lead to enrichment of hematopoietic stem cells (HSCs) with mutations in SRCAP, which encodes a chromatin remodeler that also influences DNA repair. We show that SRCAP mutations confer a selective advantage in human cells and in mice upon treatment with the anthracycline-class chemotherapeutic doxorubicin and bone marrow transplantation. Furthermore, Srcap mutations lead to a lymphoid-biased expansion, driven by loss of SRCAP-regulated H2A.Z deposition and increased DNA repair. Altogether, we demonstrate that SRCAP operates at the intersection of multiple pathways in stem and progenitor cells, offering a new perspective on the functional impact of genetic variants that promote stem cell competition in the hematopoietic system.

Study on fabrication of force transducer based on carbon nano-flake balls.

The purpose of this study was to fabricate a force sensor. A novel three-dimensional carbon-based material called a carbon nano-flake ball (CNFB) was used because it exhibits a large surface-area and high electrical conductivity. Moreover, CNFB can be easily fabricated using a one-step process via microwave plasma chemical vapor deposition. In the present study, two different methods, chemical and mechanical exfoliation, were used to fabricate the CNFB thin films. CNFEs were successfully synthesized on the silicon-based composite substrate. The substrate was constructed by the Si, SiO2, and Al2O3, where Al2O3played the role of the substrate for the force sensor while SiO2was the interface layer and was removed in the process by hydrogen fluoride (HF) solution to separate Al2O3from Silicon. The experiments showed that using sol-gel catalyst coating as pretreatment precursor, results in a larger ball-size but lower deposition density of CNFB on Al2O3substrate. By using mechanical exfoliation by polyimide (PI) tape, the CNFB grown on silicon substrate can be easily exfoliated from the substrate. PI/CNFB was successfully exfoliated from the substrate with a silver-grey color at the bottom of the CNFB which is likely to be silicon carbide (SiC) from the energy dispersive spectrometer analysis. The sheet resistance of PI/CNFB was 18.3 ± 1.0 Ω sq.-1PI/CNFB exhibits a good force sensing performance with good stability after 10 times of loading-unloading cycles and a good sensitivity of 11.6 Ω g-1.

Lanthanum-Catalyzed Stereospecific Cross-Coupling of Propargylic Substrates with Grignard Reagents.

Transition-metal-catalyzed cross-coupling of propargylic electrophiles and Grignard reagents provides densely functionalized products that are extremely useful synthetic intermediates. However, examples of conversion of propargylic derivatives to form propargyl compounds remain limited due to the challenging regioselectivity. We use LaCl3·2LiCl to catalyze propargylation of Grignard reagents in the absence of ligand in high regioselectivity and stereospecificity. The approach shows a wide substrate scope using alkyl or (hetero)aryl Grignard reagents and alkynyl electrophiles with different leaving groups. Our protocol was further applied for the formal synthesis of frondosin B. It is worth exploring methodologies utilizing the naturally abundant and relatively nontoxic lanthanum catalysts.

Valve turning towards on-cycle in cobalt-catalyzed Negishi-type cross-coupling.

Ligands and additives are often utilized to stabilize low-valent catalytic metal species experimentally, while their role in suppressing metal deposition has been less studied. Herein, an on-cycle mechanism is reported for CoCl2bpy2 catalyzed Negishi-type cross-coupling. A full catalytic cycle of this kind of reaction was elucidated by multiple spectroscopic studies. The solvent and ligand were found to be essential for the generation of catalytic active Co(I) species, among which acetonitrile and bipyridine ligand are resistant to the disproportionation events of Co(I). Investigations, based on Quick-X-Ray Absorption Fine Structure (Q-XAFS) spectroscopy, Electron Paramagnetic Resonance (EPR), IR allied with DFT calculations, allow comprehensive mechanistic insights that establish the structural information of the catalytic active cobalt species along with the whole catalytic Co(I)/Co(III) cycle. Moreover, the acetonitrile and bipyridine system can be further extended to the acylation, allylation, and benzylation of aryl zinc reagents, which present a broad substrate scope with a catalytic amount of Co salt. Overall, this work provides a basic mechanistic perspective for designing cobalt-catalyzed cross-coupling reactions.

Performance of urinary C-C motif chemokine ligand 14 for the prediction of persistent acute kidney injury: a systematic review and meta-analysis.

BACKGROUND: Urinary C-C motif chemokine ligand 14 (CCL14) has been described as an effective marker for delayed recovery of acute kidney injury (AKI), yet its efficacy has been found to vary between different trials. The goal of this research was to assess the predictive performance of urinary CCL14 as a marker for persistent AKI. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed, Embase, and Cochrane databases up to April 2023 for studies of adults (> 18 years) that reported the diagnostic performance of urinary CCL14. The sensitivity, specificity, number of events, true positive, and false positive results were extracted and evaluated. Hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the pooled test performance, and the Grading of Recommendations, Assessment, Development and Evaluations criteria were used to appraise the quality of evidence. RESULTS: We included six studies with 952 patients in this meta-analysis. The occurrence of persistent AKI among these patients was 39.6% (377/952). The pooled sensitivity and specificity results of urinary CCL14 in predicting persistent AKI were 0.81 (95% CI 0.72-0.87) and 0.71 (95% CI 0.53-0.84), respectively. The pooled positive likelihood ratio (LR) was 2.75 (95% CI 1.63-4.66), and the negative LR was 0.27 (95% CI 0.18-0.41). The HSROC with pooled diagnostic accuracy was 0.84. CONCLUSION: Our results suggest that urinary CCL14 can be used as an effective marker for predicting persistent AKI.

Protective Effect of Electroacupuncture on Chemotherapy-Induced Salivary Gland Hypofunction in a Mouse Model.

Radiotherapy and chemotherapy can impair salivary gland (SG) function, which causes xerostomia and exacerbate other side effects of chemotherapy and oral infection, reducing patients' quality of life. This animal study aimed to assess the efficacy of electroacupuncture (EA) as a means of preventing xerostomia induced by 5-fluorouracil (5-FU). A xerostomia mouse model was induced via four tail vein injections of 5-FU (80 mg/kg/dose). EA was performed at LI4 and LI11 for 7 days. The pilocarpine-stimulated salivary flow rate (SFR) and salivary glands weight (SGW) were recorded. Salivary immunoglobulin A (SIgA) and lysozyme were determined via enzyme-linked immunosorbent assay (ELISA). SG was collected for hematoxylin and eosin staining to measure acini number and acinar cell size. Tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and aquaporin 5 (AQP5) mRNA expressions in SG were quantified via RT-qPCR. 5-FU caused significant decreases in SFR, SGW, SIgA, lysozyme, AQP5 expression, and acini number, while TNF-α and IL-1ß expressions and acinar cell size were significantly increased. EA treatment can prevent 5-FU damage to the salivary gland, while pilocarpine treatment can only elevate SFR and AQP5 expression. These findings provide significant evidence to support the use of EA as an alternative treatment for chemotherapy-induced salivary gland hypofunction and xerostomia.

Cerebral Semaphorin3D is a novel risk factor for age-associated cognitive impairment.

BACKGROUND: We previously reported that miR-195 exerts neuroprotection by inhibiting Sema3A and cerebral miR-195 levels decreased with age, both of which urged us to explore the role of miR-195 and miR-195-regulated Sema3 family members in age-associated dementia. METHODS: miR-195a KO mice were used to assess the effect of miR-195 on aging and cognitive functions. Sema3D was predicted as a miR-195 target by TargetScan and then verified by luciferase reporter assay, while effects of Sema3D and miR-195 on neural senescence were assessed by beta-galactosidase and dendritic spine density. Cerebral Sema3D was over-expressed by lentivirus and suppressed by si-RNA, and effects of over-expression of Sema3D and knockdown of miR-195 on cognitive functions were assessed by Morris Water Maze, Y-maze, and open field test. The effect of Sema3D on lifespan was assessed in Drosophila. Sema3D inhibitor was developed using homology modeling and virtual screening. One-way and two-way repeated measures ANOVA were applied to assess longitudinal data on mouse cognitive tests. RESULTS: Cognitive impairment and reduced density of dendritic spine were observed in miR-195a knockout mice. Sema3D was identified to be a direct target of miR-195 and a possible contributor to age-associated neurodegeneration as Sema3D levels showed age-dependent increase in rodent brains. Injection of Sema3D-expressing lentivirus caused significant memory deficits while silencing hippocampal Sema3D improved cognition. Repeated injections of Sema3D-expressing lentivirus to elevate cerebral Sema3D for 10 weeks revealed a time-dependent decline of working memory. More importantly, analysis of the data on the Gene Expression Omnibus database showed that Sema3D levels were significantly higher in dementia patients than normal controls (p < 0.001). Over-expression of homolog Sema3D gene in the nervous system of Drosophila reduced locomotor activity and lifespan by 25%. Mechanistically, Sema3D might reduce stemness and number of neural stem cells and potentially disrupt neuronal autophagy. Rapamycin restored density of dendritic spines in the hippocampus from mice injected with Sema3D lentivirus. Our novel small molecule increased viability of Sema3D-treated neurons and might improve autophagy efficiency, which suggested Sema3D could be a potential drug target. Video Abstract CONCLUSION: Our results highlight the importance of Sema3D in age-associated dementia. Sema3D could be a novel drug target for dementia treatment.

Transition-Metal Free Electrophilic Aminations of Polyfunctional O-2,4,6-Trimethylbenzoyl Hydroxylamines with Zinc and Magnesium Organometallics.

We reported a new electrophilic amination of various primary, secondary and tertiary alkyl, benzylic, allylic zinc and magnesium organometallics with O-2,4,6-trimethylbenzoyl hydroxylamines (O-TBHAs) in 52-99 % yield. These O-TBHAs displayed an excellent long-term stability and were readily prepared from various highly functionalized secondary amines via a convenient 3 step procedure. The amination reactions showed remarkable chemoselectivity proceeding without any transition-metal catalyst and were usually complete after 1-3 h reaction time at 25 °C. Furthermore, this electrophilic amination also provided access to enantioenriched tertiary amines (up to 88 % ee) by using optically enriched secondary alkylmagnesium reagents of the type s-AlkylMgCH2 SiMe3 .

Fragile intermediate identification and reactivity elucidation in electrochemical oxidative α-C(sp3)-H functionalization of tertiary amines.

The direct α-C(sp3)-H functionalization of widely available tertiary amines holds promise for the rapid construction of complex amine architectures. The activation of C(sp3)-H bonds through electron transfer and proton transfer by oxidants, photoredox catalysis and electrochemical oxidation have received wide attention recently. In these reactions, the direct capture and identification of the key reactive radical intermediates are technically difficult due to their short life-time. Herein, an online electrochemical mass spectrometry (MS) methodology was utilized to probe the short-lived intermediates in the electrochemical oxidative α-C(sp3)-H functionalization of tertiary amines. The resulting electrochemical oxidation intermediates, α-amino radical cation and iminium cation were successfully detected. Further, the α-amino C(sp3) radical added to the double bond of a phenyl trans-styryl sulfone, yielding another C(sp3) radical that leads to the final vinylation. Based on the mass spectrometric elucidation of the reactivity of the α-amino radical, a scale-up electrochemical radical vinylation methodology was established, with which a large variety of allylic amines with broad functional group tolerance were synthesized.

Highly Regioselective Propargylation/Allenylation of Organolanthanum Reagents with Aldehydes.

The metal-mediated propargylation or allenylation of carbonyl compounds is well-adapted to the preparation of homopropargylic or allenylic alcohols, which are multifunctional intermediates in synthetic chemistry. However, the regioselectivity of reactions using propargyl or allenyl metal reagents is difficult to control, owing to the equilibrium between the two species. In our study, propargyl or allenyl organolanthanum reagents were prepared using trimethylsilylpropyne or prop-1-yn-1-ylbenzene substrates. The treatment of the organolanthanum reagents with aldehydes yielded the regioselective products, respectively. This study provides a better understanding of structural specificity and the special chemoselectivity of rare earth metal reagents.

Analgesic Efficacy of Acupuncture on Chronic Pelvic Pain: A Systemic Review and Meta-Analysis Study.

Chronic pelvic pain (CPP) is the pain occurred in the pelvic region longer than six months. The monotherapy of medicine may not adequate for the pain management of CPP and multidisciplinary approaches have been more recommended. The aim of this study is to evaluate the pain management efficacy of acupuncture compared with a control group on CPP. The articles of randomized controlled trial on CPP in PubMed and Embase databases were screened between January 2011 and September 2022 without language restriction to evaluate the treatment efficacy of acupuncture. The visual analogue scale/numerical rating scale (VAS/NRS) and total pain scores of National Institutes of Health-chronic prostatitis symptom index (NIH-CPSI) were served as outcome variables. Post-intervention mean scores were extracted and pooled for meta-analysis. Seventeen studies including 1455 patients were selected for meta-analysis. Both total pain scores of NIH-CPSI and VAS/NAS data revealed significant lower pain level in the acupuncture group than in the control group. Moreover, monotherapy with acupuncture revealed a significantly lower pain level than in the control group in both total pain scores of NIH-CPSI and VAS/NRS. These results indicated that acupuncture may have beneficial effects on pain management for CPP, even when administrated as a monotherapy.