Accumulated inflammation and fibrosis participate in atrazine induced ovary toxicity in mice.

Atrazine is a widely used herbicide in agricultural production. Previous studies have shown that atrazine affects hormone secretion and oocyte maturation in female reproduction. However, the specific mechanism by which atrazine affects ovarian function remains unclear. In this study, using a mouse gastric lavage model, we report that four weeks of atrazine exposure affects body growth, interferes with the estrous cycle, and increases the number of atretic follicles in mice. The expression levels of follicle development related factors StAR, BMP15, and AMH decreased. Metabolomic analysis revealed that atrazine activates an inflammatory response in ovarian tissue. Further studies confirmed that the expression levels of TNF-α, IL-6, and NF-κB increased in the ovaries of mice exposed to atrazine. Additionally, α-smooth muscle actin (α-SMA) accumulated in ovarian tissue, and transforming growth factor-ß (TGF-ß) signaling was activated, indicating the occurrence of tissue fibrosis. Moreover, mice exposed to atrazine produced fewer oocytes and exhibited reduced embryonic development. Furthermore, mice exposed to atrazine exhibited altered gut microbiota abundance and a disrupted colon barrier. Collectively, these findings suggest that atrazine exposure induces ovarian inflammation and fibrosis, disrupts ovarian homeostasis, and impairs follicle maturation, ultimately reducing oocyte quality.

Quantum Dot/TiO2 Nanocomposite-Based Photoelectrochemical Sensor for Enhanced H2O2 Detection Applied for Cell Monitoring and Visualization.

This work exploits the possibility of using CdSe/ZnS quantum dot (QD)-electrodes to monitor the metabolism of living cells based on photoelectrochemical (PEC) measurements. To realize that, the PEC setup is improved with respect to an enhanced photocurrent signal, better stability, and an increased signal-to-noise ratio, but also for a better biocompatibility of the sensor surface on which cells have been grown. To achieve this, a QD-TiO2 heterojunction is introduced with the help of atomic layer deposition (ALD). The heterojunction reduces the charge carrier recombination inside the semiconductor nanoparticles and improves the drift behavior. The PEC performance is carefully analyzed by adjusting the TiO2 thickness and combining this strategy with multilayer immobilizations of QDs. The optimal thickness of this coating is ≈5 nm; here, photocurrent generation can be enhanced significantly (e.g., for a single QD layer electrode by more than one order of magnitude at 0 V vs Ag/AgCl). The resulting optimized electrode is used for hydrogen peroxide (H2O2) sensing with a good sensitivity down to µmolar concentrations, reusability, stability, response rate, and repeatability. Finally, the sensing system is applied to monitor the activity of cells directly grown on top of the electrode surface.

Naringenin Promotes Gastrointestinal Motility in Mice by Impacting the SCF/c-Kit Pathway and Gut Microbiota.

Naringenin (NRG) is widely found in citrus fruits and has anti-inflammatory, hypoglycemic, and immunomodulatory effects. Previous studies have shown that NRG promotes gastrointestinal motility in mice constipation models, but there are few systematic evaluations of its effects on normal animals. This study first clarified the promotive effects of NRG on gastric emptying and small intestine propulsion (p < 0.01). NRG can also regulate the release of gastrointestinal hormones, including enhancing gastrin (GAS) and motilin (MTL) (p < 0.01), while reducing vasoactive intestinal peptide (VIP) secretion (p < 0.01). Using NRG to stimulate the isolated stomach, duodenum, and colon showed similar promotive effects to those observed in vivo (p < 0.01). A Western blot analysis indicated that this effect may be mediated by increasing the expression of stem cell factor (SCF) and its receptor (c-Kit) in these three segments, thus regulating their downstream pathways. It is worth noting that NRG can also increase the proportion of beneficial bacteria (Planococcaceae, Bacteroides acidifaciens, Clostridia_UCG-014) in the intestine and reduce the quantity of harmful bacteria (Staphylococcus). These findings provide a new basis for the application of NRG.

Transdermal microarrayed electroporation for enhanced cancer immunotherapy based on DNA vaccination.

Despite the tremendous clinical potential of nucleic acid-based vaccines, their efficacy to induce therapeutic immune response has been limited by the lack of efficient local gene delivery techniques in the human body. In this study, we develop a hydrogel-based organic electronic device (µEPO) for both transdermal delivery of nucleic acids and in vivo microarrayed cell electroporation, which is specifically oriented toward one-step transfection of DNAs in subcutaneous antigen-presenting cells (APCs) for cancer immunotherapy. The µEPO device contains an array of microneedle-shaped electrodes with pre-encapsulated dry DNAs. Upon a pressurized contact with skin tissue, the electrodes are rehydrated, electrically triggered to release DNAs, and then electroporate nearby cells, which can achieve in vivo transfection of more than 50% of the cells in the epidermal and upper dermal layer. As a proof-of-concept, the µEPO technique is employed to facilitate transdermal delivery of neoantigen genes to activate antigen-specific immune response for enhanced cancer immunotherapy based on a DNA vaccination strategy. In an ovalbumin (OVA) cancer vaccine model, we show that high-efficiency transdermal transfection of APCs with OVA-DNAs induces robust cellular and humoral immune responses, including antigen presentation and generation of IFN-γ+ cytotoxic T lymphocytes with a more than 10-fold dose sparing over existing intramuscular injection (IM) approach, and effectively inhibits tumor growth in rodent animals.

Multicopy Chromosome Integration and Deletion of Negative Global Regulators Significantly Increased the Heterologous Production of Aborycin in Streptomyces coelicolor.

Aborycin is a type I lasso peptide with a stable interlocked structure, offering a favorable framework for drug development. The aborycin biosynthetic gene cluster gul from marine sponge-associated Streptomyces sp. HNS054 was cloned and integrated into the chromosome of S. coelicolor hosts with different copies. The three-copy gul-integration strain S. coelicolor M1346::3gul showed superior production compared to the one-copy or two-copy gul-integration strains, and the total titer reached approximately 10.4 mg/L, i.e., 2.1 times that of the native strain. Then, five regulatory genes, phoU (SCO4228), wblA (SCO3579), SCO1712, orrA (SCO3008) and gntR (SCO1678), which reportedly have negative effects on secondary metabolism, were further knocked out from the M1346::3gul genome by CRISPR/Cas9 technology. While the ΔSCO1712 mutant showed a significant decrease (4.6 mg/L) and the ΔphoU mutant showed no significant improvement (12.1 mg/L) in aborycin production, the ΔwblA, ΔorrA and ΔgntR mutations significantly improved the aborycin titers to approximately 23.6 mg/L, 56.3 mg/L and 48.2 mg/L, respectively, which were among the highest heterologous yields for lasso peptides in both Escherichia coli systems and Streptomyces systems. Thus, this study provides important clues for future studies on enhancing antibiotic production in Streptomyces systems.

CdSe/TiO2NTs Heterojunction-Based Nonenzymatic Photoelectrochemical Sensor for Glucose Detection.

Compared with a single semiconductor, the heterojunction formed by two different semiconductors usually has higher light utilization and better photoelectric performance. By using stable TiO2 nanotubes as the main subject, CdSe/TiO2NTs heterojunctions were synthesized by a hydrothermal method. XRD, TEM, SEM, PL, UV-vis, and EIS were used to characterize the fabricated CdSe/TiO2NTs. Under visible light irradiation, CdSe/TiO2NTs heterojunctions exhibited a higher absorption intensity and lower degree of photogenerated carrier recombination than TiO2. The electrons and holes were proven to be effectively separated in this heterojunction via theoretical calculation. Under CdSe/TiO2NTs' optimal conditions, the glucose concentrations (10-90 µM) had a linear relationship with the photocurrent value, and the detection limit was 3.1 µM. Moreover, the CdSe/TiO2NTs sensor exhibited good selectivity and stability. Based on the experimental data and theoretical calculations, its PEC sensing mechanism was also illuminated.

The tendency of anemia of inflammation in periodontal diseases.

Anemia of inflammation (AI) is associated with inflammatory diseases, and inflammation-induced iron metabolism disorder is the major pathogenic factor. Earlier studies have reported a tendency of AI in periodontitis patients, but the explicit relationship and possible pathological mechanisms remain unclear. Here, the analyses of both periodontitis patients and a mouse model of ligature-induced experimental periodontitis showed that periodontitis was associated with lower levels of hemoglobin and hematocrit with evidence of systemic inflammation (increased white blood cell levels) and evidence of iron restriction (low serum iron along with a high serum hepcidin and ferritin levels), in accordance with the current diagnosis criteria for AI. Moreover, periodontal therapy improved the anemia status and iron metabolism disorders. Furthermore, the increased level of hepcidin and significant correlation between hepcidin and key indicators of iron metabolism emphasized the pivotal role of hepcidin in the pathogenesis of periodontitis-related AI. Administration of the signal transducer and activator of transcription 3 (STAT3) inhibitors Stattic suggested that the IL-6-STAT3-hepcidin signaling pathway participated in this regulatory process. Together, these findings demonstrated that periodontitis should be considered an inflammatory disease that contributes to the development of AI; furthermore, IL-6-STAT3-hepcidin signaling pathway plays a key regulatory role in the pathogenesis of periodontitis-related AI. Our study will provide new insights into the systemic effects of periodontitis, while meaningfully expanding the spectrum of inflammatory diseases that contribute to AI.

Tailoring of the photocatalytic activity of CeO2 nanoparticles by the presence of plasmonic Ag nanoparticles.

The present study investigates basic features of a photoelectrochemical system based on CeO2 nanoparticles fixed on gold electrodes. Since photocurrent generation is limited to the absorption range of the CeO2 in the UV range, the combination with metal nanoparticles has been studied. It can be shown that the combination of silver nanoparticles with the CeO2 can shift the excitation range into the visible light wavelength range. Here a close contact between both components has been found to be essential and thus, hybrid CeO2@Ag nanoparticles have been prepared and analyzed. We have collected arguments that electron transfer occurs between both compositional elements of the hybrid nanoparticles.The photocurrent generation can be rationalized on the basis of an energy diagram underlying the necessity of surface plasmon excitation in the metal nanoparticles, which is also supported by wavelength-dependent photocurrent measurements. However, electrochemical reactions seem to occur at the CeO2 surface and consequently, the catalytic properties of this material can be exploited as exemplified with the photoelectrochemical reduction of hydrogen peroxide. It can be further demonstrated that the layer-by layer technique can be exploited to create a multilayer system on top of a gold electrode which allows the adjustment of the sensitivity of the photoelectrochemical system. Thus, with a 5-layer electrode with hybrid CeO2@Ag nanoparticles submicromolar hydrogen peroxide concentrations can be detected.

Environmental significance of atmospheric nitrogen deposition in the transition zone between the Tibetan Plateau and arid region.

The ecological effect of atmospheric N deposition has become a hot research point along with intensive human activities and global climatic change. As the transition zone between the Tibetan Plateau and the arid region, the Qilian Mountains are important ecological barriers and source regions of inland rivers in northwest China. However, the quantification of N deposition in the transition zone between the Tibetan Plateau (TP) and the arid region remains unclear, primarily due to the lack of in situ measurements. Hence, an observational study was conducted on the Qilian Mountains, and precipitation data were collected. Approximately 1382 samples were collected and analyzed regarding their characteristics and environmental effects of the atmospheric N wet deposition. The annual wet deposition of atmospheric N was 10.05 kg/hm2, and showed a decreasing trend from the south to the north of the Qilian Mountains. NO3--N deposition was the main form of wet deposition of atmospheric N on the Qilian Mountains, accounting for 73.83% of the DIN deposition. Additionally, altitude, meteorological factors, and ecosystem types were found to influence the wet deposition of atmospheric N. The contribution of NO3--N to the wet deposition of atmospheric N in meadows, forests, grasslands, farmlands, and towns was 48.38%, 71.55%, 77.54%, 69.61%, and 82.84%, respectively. This study provides a scientific basis for the effective management and sustainable development of environmental protection in the transition zone between the TP and the arid region. The results showed that relevant policies, as well as scientific and governmental measures, could contribute to reducing N deposition effectively. However, the further mitigation measures should be proposed and strictly enforced.

Highly Sensitive Temperature-Pressure Bimodal Aerogel with Stimulus Discriminability for Human Physiological Monitoring.

Multimodal sensor with high sensitivity, accurate sensing resolution, and stimuli discriminability is very desirable for human physiological state monitoring. A dual-sensing aerogel is fabricated with independent pyro-piezoresistive behavior by leveraging MXene and semicrystalline polymer to assemble shrinkable nanochannel structures inside multilevel cellular walls of aerogel for discriminable temperature and pressure sensing. The shrinkable nanochannels, controlled by the melt flow-triggered volume change of semicrystalline polymer, act as thermoresponsive conductive channels to endow the pyroresistive aerogel with negative temperature coefficient of resistance of -10.0% °C-1 and high accuracy within 0.2 °C in human physiological temperature range of 30-40 °C. The flexible cellular walls, working as pressure-responsive conductive channels, enable the piezoresistive aerogel to exhibit a pressure sensitivity up to 777 kPa-1 with a detectable pressure limit of 0.05 Pa. The pyro-piezoresistive aerogel can detect the temperature-dependent characteristics of pulse pressure waveforms from artery vessels under different human body temperature states.

Legal determination of surrogate child parenthood in China.

Commercial surrogacy is neither prohibited nor approved in China. As the underground surrogacy market keeps expanding fast, the disputes over parenthood of surrogate child occur more and more frequently. Since there are no specific rules for surrogacy, Chinese courts have to make legal determination by applying current laws. This article firstly analyses the contradictions of existing laws and regulations on natural parenthood when apply them in the cases of surrogacy. In China, since the natural parenthood is built on reproductive connections between parents and child, this article provides a typology of surrogacy in terms of the reproductive role each party has played. By combining it with the case study, the judicial views on different issues are presented. This article further discusses the inadequacies of current legal determination of parenthood, ethical controversies in surrogacy and recommends some suggestions on regulating the surrogacy and protecting the rights and interests of women and children.

CdS-Modified TiO2 Nanotubes with Heterojunction Structure: A Photoelectrochemical Sensor for Glutathione.

The formation of heterojunction structures can effectively prevent the recombination of photogenerated electron-hole pairs in semiconductors and result in the enhancement of photoelectric properties. Using TiO2 nanotubes (prepared using the hydrothermal-impregnation method) as carriers, CdS-TiO2NTs were fabricated as a photoelectrochemical (PEC) sensor, which can be used under visible light and can exhibit good PEC performance due to the existence of the heterojunction structure. The experimental results show that the prepared CdS-TiO2NTs electrode had a linear response to 2-16 mM glutathione (GSH). The sensor's sensitivity and detection limit (LOD) were 102.9 µA·mM-1 cm-2 and 27.7 µM, respectively. Moreover, the biosensor had good stability, indicating the potential application of this kind of heterojunction PEC biosensor.

Bronchial Artery Chemoembolization for Hemoptysis in Advanced Primary Lung Cancer.

BACKGROUND: To evaluate the safety and effectiveness of bronchial arterial infusion chemoembolization (BAICE) for lung cancer with hemoptysis. PATIENTS AND METHODS: Retrospectively analyze clinical data of patients undergoing BAICE for the treatment of lung cancer with hemoptysis, evaluate the clinical efficacy of this approach, observe postoperative adverse reactions, and analyze hemoptysis-free survival (HFS) and overall survival (OS). RESULTS: All 187 patients underwent BAICE with technical success rate of 100%, clinical success rate of 86.6%, clinical failure rate of 13.4%. After BAICE, the tumor curative effect was evaluated as complete remission in 56 cases, partial remission in 82 cases, stable disease in 26 cases, and progressive disease in 6 cases. The objective response rate was 73.8%, and the disease control rate was 87.7%. Median HFS of the 154 clinically successful cases was 10.5 months (95% confidence interval [CI]: 8.11-11.89). The degree of hemoptysis (massive hemoptysis hazard ratio [HR] = 5.9, 95% CI: 3.43-10.16, P = .00) and cavitary lung mass (HR = 2.39, 95% CI: 1.44-3.99, P = .001), were significantly related to a reduction in HFS after BAICE. The 6-month and 12-month survival rates were 66.5% and 45.6%, respectively. The median OS of clinically successful cases was 13.0 months (95% CI: 11.22-14.77). The median OS of 16 clinically failed cases was 2.0 months (95% CI: 0.41-2.45) (P < .001). All adverse events were grade 1. CONCLUSION: BAICE for advanced lung cancer with hemoptysis is safe, effective, and tolerable.

Ultrasensitive photoelectrochemical microcystin-LR immunosensor using carboxyl-functionalized graphene oxide enhanced gold nanoclusters for signal amplification.

An ultrasensitive photoelectrochemical (PEC) immunosensor based on gold nanoclusters (AuNCs) with 11-mercaptoundecanoic acid (MUA) ligands was fabricated for determination of microcystin-LR (MC-LR). The PEC immunosensor was developed by loading the monoclonal MC-LR antibody (Ab) to the MUA-AuNCs modified gold electrodes. After different measurement conditions being optimized, silver nanoparticles (AgNPs), gold nanorods (AuNRs), graphene oxide (GO) and carboxyl-functionalized graphene oxide (cGO) were introduced into MUA-AuNCs to enhance the sensing properties. The experimental result revealed that the sensitivity of PEC immunosensors was enhanced by both their photoelectrochemical properties and antibody loading properties with dependent relationship, which was different from the enhancement strategy of PEC sensors based on redox reactions. Among different hybrid nanocomposites, MUA-AuNCs/cGO not only improved the photoelectrochemical properties, but also loaded more antibodies for sensing, which resulted in best sensing performance. Thus, a universal method was proposed to enhance the sensing performance of PEC immunosensors based on impedance changes. Finally, MUA-AuNCs/cGO based PEC immunosensors exhibited a wide linear range of 0.001 nM-1000 nM with low detection limit of 0.011 pM (S/N = 3) for MC-LR determination. Meanwhile, the designed PEC immunosensors showed high selectivity, reproducibility and specificity, which provided the promising applications in aquatic environment.

Albumin Fusion at the N-Terminus or C-Terminus of HM-3 Leads to Improved Pharmacokinetics and Bioactivities.

HM-3, an integrin antagonist, exhibits anti-tumor biological responses and therefore has potential as a therapeutic polypeptide. However, the clinical applications of HM-3 are limited by its short half-life. In this study, we genetically fused human serum albumin (HSA) to the N or C-terminus of HM-3 to improve HM-3 pharmacokinetics. HM-3/HSA proteins were successfully expressed in Pichia pastoris and displayed improved pharmacokinetic properties and stability. Among them, the half-life of HM-3-HSA was longer than HSA-HM-3. In vitro, the IC50 values of HSA-HM-3 and HM-3-HSA were 0.38 ± 0.14 µM and 0.25 ± 0.08 µM in B16F10 cells, respectively. In vivo, the inhibition rates of B16F10 tumor growth were 36% (HSA-HM-3) and 56% (HM-3-HSA), respectively, indicating antitumor activity of HM-3-HSA was higher than HSA-HM-3. In conclusion, these results suggested that the HM-3/HSA fusion protein might be potential candidate HM-3 agent for treatment of melanoma and when HSA was fused at the C-terminus of HM-3, the fusion protein had a higher stability and activity.

Digital Workflow for Full-Arch Immediate Implant Placement Using a Stackable Surgical Guide Fabricated Using SLM Technology.

The failing dentition of partially edentulous individuals may be used as an initial reference for stackable restrictive surgical guides during full-arch immediate implant placement. The stackable guide option derived from a digital workflow increases the predictability of the performance of bone reduction, immediate implant placement, and immediate loading of provisional implant-supported fixed dental prostheses. The present paper aims to report a practical approach to design and produce a metal framework with occlusal rests to facilitate the use of a tooth-supported surgical guide when full-arch immediate implant placement is indicated in patients with failing dentition.

Investigation of electron transfer between single plasmon and graphene by dark field spectroscopy.

We investigated the electron transfer time between single plasmonic gold nanoparticles and graphene with our home-build spectral imaging dark-field microscope. The process of electron transfer is supposed to be shuttling of hot electrons on the nanoparticle-graphene interface, resulting in a slight broadening of the scattering spectrum. For detecting the minor spectrum broadening, we firstly characterized our setup systematically and then calibrated its intrinsic error. We found the mechanism of a common but normally neglected setup error, scattering spectrum broadening, which is caused by the bandwidth of the incident light and could exist in most fast dark-field microscopy setups. We corrected the linewidth of plasmon scattering spectra theoretically by both numerical and analytical solution, and then realized it experimentally by tuning the bandwidth of the incident light. After calibration, we revisited scattering spectra of 700 small aspect ratio nanorods on glass and monolayer graphene revealing a typical 14.3 meV linewidth broadening. Furthermore, we measured four other kinds of gold nanoparticles on glass, mono- and bilayer graphene for deeper understanding of the electron transfer. A common linewidth broadening is found for each kind of particle agreeing well with previous theory. However, an unconventional linewidth narrowing is also discovered for big particles whose resonance wavelength is close to the near infrared region. It implies a competitive mechanism in the electron transfer process which could not only increase the damping of small particles, causing a linewidth broadening, but also simplify the electric field pattern for big particles, leading to a linewidth narrowing, according to our Mie theory simulation.

Introducing visible-light sensitivity into photocatalytic CeO2 nanoparticles by hybrid particle preparation exploiting plasmonic properties of gold: enhanced photoelectrocatalysis exemplified for hydrogen peroxide sensing.

In this report we combine the catalytic properties of CeO2 nanoparticles with their transduction ability for photoelectrochemical sensing. This study highlights the usage of CeO2 providing catalytic activity towards H2O2, but only with a limited excitation range in the UV for the construction of a sensing system. In order to improve the photoelectrocatalysis of CeO2 nanoparticles by extending their excitation to visible light, Au/CeO2 core/shell hybrid nanoparticles have been synthesized. The hybrid nanoparticles are fixed on electrodes, allowing for the generation of photocurrents, the direction of which can be controlled by the electrode potential (without bias). The application of the hybrid nanoparticles results in an enhanced photocurrent amplitude under white light illumination as compared to the pure CeO2 nanoparticles. Wavelength-dependent measurements confirm the participation of the Au core in the signal transduction. This can be explained by improved charge carrier generation within the hybrid particles. Thus, by using a plasmonic element the photoelectochemical response of a catalytic nanoparticle (i.e. CeO2) has been spectrally extended. The effect can be exploited for sensorial hydrogen peroxide detection. Here higher photocatalytic current responses have been found for the hybrid particles fixed to gold electrodes although the catalytic reduction has been comparable for both types of nanoparticles. Thus, it can be demonstrated that Au/CeO2 core-shell nanoparticles allow the utilization of visible light for photoelectrochemical hydrogen peroxide (H2O2) detection with improved sensitivity under white light illumination or application of such particles with only visible light excitation, which is not possible for pure CeO2. With help of the layer-by-layer (LbL) technique for nanoparticle immobilization, the electrode response can be adjusted and with a 5 layers electrode a low detection limit of about 3 µM H2O2 with a linear detection range up to 2000 µM is obtained.

Occurrence of Gastrointestinal Parasites in Camels in the Tianshan Mountains Pastoral Area in China.

INTRODUCTION: Gastrointestinal parasites are some of the most common pathogens which are seriously harmful to the camel's health. The infection status of gastrointestinal parasites in camels (Camelus bactrianus) in the Tianshan Mountains pastoral area in China is still unclear. The aim of this study was to investigate the species and infection intensity of gastrointestinal tract parasites in local camels. MATERIAL AND METHODS: A total of 362 fresh faecal samples were collected and examined for parasite eggs using the saturated saline floating and natural sedimentation method. The parasite eggs were subjected to morphological and molecular examination and identification, and the infection rate and mean intensity of the parasites were analysed. RESULTS: A total of 15 gastrointestinal tract parasite species' eggs were identified, with a detection rate of 100%. Ostertagia spp. (100%) and Trichostrongylus spp. (98.1%) were dominant. Camels were often coinfected by 5-14 species. The average number of eggs per gram of faeces was higher for Ostertagia spp. (298), Haemonchus contortus (176) and Nematodirus spp. (138). The number of species of parasites infecting young camels was significantly lower than that of adult camels, but the infection intensity in young camels was significantly higher. CONCLUSION: Gastrointestinal parasites were highly prevalent in camels from the Tianshan Mountains pastoral area in China. This finding provides important epidemiological data for the prevention and control of associated infections in camels.

Foot reflexology in the management of functional constipation: A systematic review and meta-analysis.

BACKGROUND: Foot reflexology has been considered an important complementary therapy for many health-related symptoms, especially for some chronic conditions such as anxiety, stress, pain and fatigue. Some studies also showed that foot reflexology had a significant effect on functional constipation, whereas some studies did not. The effect of foot reflexology on functional constipation remains controversial. Therefore, an evidence-based systematic review and meta-analysis of randomised controlled trials were conducted to investigate the effect of foot reflexology on functional constipation. METHODS: Randomised controlled trials were identified by searching five electronic databases and hand-searching eligible reference lists. Studies that reported the effect of foot reflexology on functional constipation were included. Two reviewers performed the study screening, quality assessment and data extraction. Any discrepancy was discussed with a third reviewer. Quantitative synthesis was conducted for the same outcome measurements by calculating weighted risk ratios. RESULTS: A total of 203 records were identified, of which seven were eligible. Overall, foot reflexology significantly increased the curative ratio, with a pooled risk ratio of 1.27 (95% CI: 1.16, 1.40, p < 0.00001). Three trials compared the improvement of constipation-related symptoms after intervention in both the experimental and control groups by evaluating the constipation-related symptom scores. The results all showed that foot reflexology can effectively improve constipation-related symptoms. However, one trial reported that foot reflexology had no significant effect on stool frequency and stool consistency. Two studies indicated that foot reflexology significantly reduced the recurrence rate of functional constipation. One study reported the effect of foot reflexology on compliance with the toilet training, diet and motivation. Nevertheless, no significant improvement was detected. CONCLUSION: Foot reflexology is an effective complementary therapy for treating functional constipation. However, because of the small number of included studies and their small sample sizes, the current evidence was insufficient to support the effectiveness of foot reflexology in reducing the recurrence rate, improving the constipation-related symptom, and compliance with toilet training, diet and motivation. Randomised controlled trials with long-term follow-up are needed for further investigation.