Material assembly from collective action of shape-changing polymers.

Some animals form transient, responsive and solid-like ensembles through dynamic structural interactions. These ensembles demonstrate emergent responses such as spontaneous self-assembly, which are difficult to achieve in synthetic soft matter. Here we use shape-morphing units comprising responsive polymers to create solids that self-assemble, modulate their volume and disassemble on demand. The ensemble is composed of a responsive hydrogel, liquid crystal elastomer or semicrystalline polymer ribbons that reversibly bend or twist. The dispersions of these ribbons mechanically interlock, inducing reversible aggregation. The aggregated liquid crystal elastomer ribbons have a 12-fold increase in the yield stress compared with cooled dispersion and contract by 34% on heating. Ribbon type, concentration and shape dictate the aggregation and govern the global mechanical properties of the solid that forms. Coating liquid crystal elastomer ribbons with a liquid metal begets photoresponsive and electrically conductive aggregates, whereas seeding cells on hydrogel ribbons enables self-assembling three-dimensional scaffolds, providing a versatile platform for the design of dynamic materials.

Mediating pathways between neighborhood disadvantage and cardiovascular risk: Quasi-experimental evidence from a Danish refugee dispersal policy.

Research has documented that neighborhood disadvantage is associated with increased cardiovascular disease risk, but it is unclear which mechanistic pathways mediate this association across the life course. Leveraging a natural experiment in which refugees to Denmark were quasi-randomly assigned to neighborhoods across the country during 1986-1998 and using 30 years of follow-up data from population and health registers, we assessed whether and how individual-level poverty, unstable employment, and poor mental health mediate the relation between neighborhood disadvantage and the risk of hypertension, hyperlipidemia, and type 2 diabetes among Danish refugees (N= 40,811). Linear probability models using the discrete time-survival framework showed that neighborhood disadvantage was associated with increased risk of hypertension (0.05 percentage points [pp] per year [95%CI -0.00, 0.10]); hyperlipidemia (0.03 pp per year [95%CI -0.01, 0.07]), and diabetes (0.01 pp per year (95%CI -0.02, 0.03)). The Baron-Kenny product-of-coefficients method for counterfactual mediation analysis indicated that cumulative income mediated 6%-28% of the disadvantage effect on these outcomes. We find limited evidence of mediation by unstable employment and poor mental health. This study informs our theoretical understanding of the pathways linking neighborhood disadvantage with cardiovascular disease risk and identifies income security as a promising point of intervention in future research.

Gastroparesis might not be uncommon in patients with diabetes mellitus in a real-world clinical setting: a cohort study.

BACKGROUND: This study investigated the frequency of diabetic gastroparesis and associated risk factors in a real-world clinical setting. METHODS: This retrospective cross-sectional study included patients who underwent assessments of solid gastric emptying time (GET) by technetium-99 m scintigraphy between May 2019 and December 2020. We categorized patients into three groups according to gastric retention of technetium-99 m: rapid (< 65% at 1 h or < 20% at 2 h), normal (≤60% at 2 h and/or ≤ 10% at 4 h), and delayed (> 60% at 2 h and/or > 10% at 4 h). RESULTS: Patients with diabetes mellitus (DM) were more likely to show abnormal GET than those without DM (119 [70.8%] vs. 16 [44.4%]). The mean glycated A1c was 10.3% in DM patients. DM patients with normal GET were significantly younger (57.2 years, P = 0.044) than those with delayed (65.0 years) or rapid GET (60.2 years). Fasting glucose levels were the lowest in the normal GET group and the highest in the rapid GET group (delayed: 176.3 mg/dL, normal: 151.2 mg/dL, rapid: 181.0 mg/dL, P = 0.030). However, glycated A1c was not significantly different among the delayed, normal, and rapid GET groups in patients with DM. Patients with delayed and rapid GET showed a higher frequency of retinopathy (6.0 vs. 15.5%, P = 0.001) and peripheral neuropathy (11.3 vs. 24.4%, P = 0.001) than those with normal GET. In the multinomial logistic regression analysis, retinopathy demonstrated a positive association with delayed GET, while nephropathy showed a significant negative correlation. CONCLUSION: DM gastroparesis in the clinical setting was not uncommon. Abnormal GET, including delayed and rapid GET, was associated with DM retinopathy or peripheral neuropathy.

Ceramide synthase 4 overexpression exerts oncogenic properties in breast cancer.

BACKGROUND: Ceramide, a bioactive signaling sphingolipid, has long been implicated in cancer. Members of the ceramide synthase (CerS) family determine the acyl chain lengths of ceramides, with ceramide synthase 4 (CerS4) primarily generating C18-C20-ceramide. Although CerS4 is known to be overexpressed in breast cancer, its role in breast cancer pathogenesis is not well established. METHODS: To investigate the role of CerS4 in breast cancer, public datasets, including The Cancer Genome Atlas (TCGA) and two Gene Expression Omnibus (GEO) datasets (GSE115577 and GSE96058) were analyzed. Furthermore, MCF-7 cells stably overexpressing CerS4 (MCF-7/CerS4) as a model for luminal subtype A (LumA) breast cancer were produced, and doxorubicin (also known as Adriamycin [AD])-resistant MCF-7/ADR cells were generated after prolonged treatment of MCF-7 cells with doxorubicin. Kaplan-Meier survival analysis assessed the clinical significance of CERS4 expression, while Student's t-tests or Analysis of Variance (ANOVA) compared gene expression and cell viability in different MCF-7 cell lines. RESULTS: Analysis of the public datasets revealed elevated CERS4 expression in breast cancer, especially in the most common breast cancer subtype, LumA. Persistent CerS4 overexpression in MCF-7 cells activated multiple cancer-associated pathways, including pathways involving sterol regulatory element-binding protein, nuclear factor kappa B (NF-κB), Akt/mammalian target of rapamycin (mTOR), and ß-catenin. Furthermore, MCF-7/CerS4 cells acquired doxorubicin, paclitaxel, and tamoxifen resistance, with concomitant upregulation of ATP-binding cassette (ABC) transporter genes, such as ABCB1, ABCC1, ABCC2, ABCC4, and ABCG2. MCF-7/CerS4 cells were characterized by increased cell migration and epithelial-mesenchymal transition (EMT). Finally, CERS4 knockdown in doxorubicin-resistant MCF-7/ADR cells resulted in reduced activation of cancer-associated pathways (NF-κB, Akt/mTOR, ß-catenin, and EMT) and diminished chemoresistance, accompanied by ABCB1 and ABCC1 downregulation. CONCLUSIONS: Chronic CerS4 overexpression may exert oncogenic effects in breast cancer via alterations in signaling, EMT, and chemoresistance. Therefore, CerS4 may represent an attractive target for anticancer therapy, especially in LumA breast cancer.

Neighbourhood socioeconomic disadvantage and psychiatric disorders among refugees: a population-based, quasi-experimental study in Denmark.

PURPOSE: Refugees are vulnerable to psychiatric disorders because of risk factors linked to migration. Limited evidence exist on the impact of the neighbourhood in which refugee resettle. We examined whether resettling in a socioeconomically disadvantaged neighbourhood increased refugees' risk of psychiatric disorders. METHODS: This register-based cohort study included 42,067 adults aged 18 years and older who came to Denmark as refugees during 1986-1998. Resettlement policies in those years assigned refugees in a quasi-random fashion to neighbourhoods across the country. A neighbourhood disadvantage index was constructed using neighbourhood-level data on income, education, unemployment, and welfare receipt. Main outcomes were psychiatric diagnoses and psychiatric medication usage ascertained from nationwide patient and prescription drug registers, with up to 30-year follow-up. Associations of neighbourhood disadvantage with post-migration risk of psychiatric disorders were examined using Cox proportional hazards and linear probability models adjusted for individual, family, and municipality characteristics. RESULTS: The cumulative risk of psychiatric diagnoses and medication was 13.7% and 46.1%, respectively. Refugees' risk of psychiatric diagnoses and psychiatric medication usage was higher among individuals assigned to high-disadvantage compared with low-disadvantage neighbourhoods in analyses including fixed effects for assigned municipality (psychiatric diagnoses: hazard ratio (HR) = 1.14, 95% CI 1.04, 1.25; psychiatric medication: HR = 1.05, 95% CI 1.00, 1.11). Consistent results were found using linear probability models. Results for diagnostic categories and subclasses of medications suggested that the associations were driven by neurotic and stress-related disorders and use of anxiolytic medications. CONCLUSION: Resettlement in highly disadvantaged neighbourhoods was associated with an increase in refugees' risk of psychiatric disorders, suggesting that targeted placement of newly arrived refugees could benefit refugee mental health. The results contribute quasi-experimental evidence to support links between neighbourhood characteristics and health.

Drug Development from Natural Products Based on the Pathogenic Mechanism of Asthma.

Asthma is a chronic inflammatory disease of the pulmonary system associated with many wheeze-to-sleep apnea complications that may lead to death. In 2019, approximately 262 million patients suffered from asthma, and 455 thousand died from the disease worldwide. It is a more severe health problem in children and older adults, and as the aging of society intensifies, the problem will continue to worsen. Asthma inducers can be classified as indoor and outdoor allergens and can cause asthma due to their repeated invasion. There are several theories about asthma occurrence, such as the imbalance between Th1 and Th2, inflammation in the pulmonary system, and the abnormal apoptosis/cell proliferation of cells related to asthma. Although there are many medications for asthma, as it is an incurable disease, the purpose of the drugs is only to suppress the symptoms. The current drugs can be divided into relievers and controllers; however, as they have many adverse effects, such as immune suppression, growth retardation, promotion of cataracts, hyperactivity, and convulsions, developing new asthma drugs is necessary. Although natural products can have adverse effects, the development of asthma drugs from natural products may be beneficial, as some have anti-asthmatic effects such as immune modulation, anti-inflammation, and/or apoptosis modulation.

School racial segregation and long-term cardiovascular health among Black adults in the US: A quasi-experimental study.

BACKGROUND: Cardiovascular disease (CVD) disproportionately affects Black adults in the United States. This is increasingly acknowledged to be due to inequitable distribution of health-promoting resources. One potential contributor is inequities in educational opportunities, although it is unclear what aspects of education are most salient. School racial segregation may affect cardiovascular health by increasing stress, constraining socioeconomic opportunities, and altering health behaviors. We investigated the association between school segregation and Black adults' CVD risk. METHODS AND FINDINGS: We leveraged a natural experiment created by quasi-random (i.e., arbitrary) timing of local court decisions since 1991 that released school districts from court-ordered desegregation. We used the Panel Study of Income Dynamics (PSID) (1991 to 2017), linked with district-level school segregation measures and desegregation court order status. The sample included 1,053 Black participants who ever resided in school districts that were under a court desegregation order in 1991. The exposure was mean school segregation during observed schooling years. Outcomes included several adult CVD risk factors and outcomes. We fitted standard ordinary least squares (OLS) multivariable linear regression models, then conducted instrumental variables (IV) analysis, using the proportion of schooling years spent in districts that had been released from court-ordered desegregation as an instrument. We adjusted for individual- and district-level preexposure confounders, birth year, and state fixed effects. In standard linear models, school segregation was associated with a lower probability of good self-rated health (-0.05 percentage points per SD of the segregation index; 95% CI: -0.08, -0.03; p < 0.001) and a higher probability of binge drinking (0.04 percentage points; 95% CI: 0.002, 0.07; p = 0.04) and heart disease (0.01 percentage points; 95% CI: 0.002, 0.15; p = 0.007). IV analyses also found that school segregation was associated with a lower probability of good self-rated health (-0.09 percentage points; 95% CI: -0.17, -0.02, p = 0.02) and a higher probability of binge drinking (0.17 percentage points; 95% CI: 0.04, 0.30, p = 0.008). For IV estimates, only binge drinking was robust to adjustments for multiple hypothesis testing. Limitations included self-reported outcomes and potential residual confounding and exposure misclassification. CONCLUSIONS: School segregation exposure in childhood may have longstanding impacts on Black adults' cardiovascular health. Future research should replicate these analyses in larger samples and explore potential mechanisms. Given the recent rise in school segregation, this study has implications for policies and programs to address racial inequities in CVD.

Streptooctatins A and B, fusicoccane-type diterpenoids with autophagic activity from Streptomyces sp. KCB17JA11.

Two new fusicoccane-type diterpenoids, streptooctatins A (1) and B (2), together with a known compound cyclooctatin (3) were isolated from Streptomyces sp. KCB17JA11. The structures of 1 and 2 were determined by analyzing spectroscopic and spectrometric data from 1D and 2D NMR and HRESIMS experiments. Compounds 1 and 2 induced EGFP-LC3 puncta indicating autophagic activities against HeLa cells without cytotoxicity.

Association between smokeless tobacco use and cigarette smoking amount by age.

BACKGROUND: The use of smokeless tobacco has increased worldwide among young people. This study aimed to investigate the association between smokeless tobacco use and cigarette smoking amount in adult smoker groups stratified by age. METHOD: 2013-2015 National Health Interview Survey was used. A total of 19,635 subjects were included in our analysis. Propensity score matching was used to adjust for selection and any other bias. Generalized estimating equation was used to analyze the association between smokeless tobacco use and cigarette smoking amount by age. RESULTS: All 580 smokeless tobacco users were matched to 2,900 non-smokeless tobacco users. Among those who were aged under 30, smokeless tobacco use was positively associated with the number of cigarettes used per day. Smokeless tobacco users who were aged under 30 and tried quitting smoking used more cigarettes than those who did non-smokeless tobacco users. CONCLUSIONS: The present study revealed that among those who were aged under 30, smokeless tobacco use was positively associated with the number of cigarettes used per day. This study could contribute to understand the behaviors and tendencies of smoking in young adulthood and to establish effective smoking cessation methods for their age.

Association between hyperuricemia and metabolic risk components in Korean women.

The researchers evaluated the association between hyperuricemia and metabolic risk components in Korean women of reproductive and postmenopausal ages. The study data were collected from the Korea National Health and Nutrition Examination Survey 2016. Among a total of 4305 female participants, the data of 2958 women were analyzed. Of the 2958 participants, 57.6% (n = 1508) were of reproductive age. After adjusting for factors, hyperuricemia was significantly associated with abdominal obesity (OR 4.30, p = .046), high blood pressure (OR 3.23, p = .002), and hypertriglyceridemia (OR 3.08, p = .005) in reproductive women. In contrast, no metabolic risk was significantly associated with hyperuricemia in postmenopausal women.

Engineering Tools for Regulating Hypoxia in Tumour Models.

Major advances in the field of genomic technologies have led to an improvement in cancer diagnosis, classification and prognostication. However, many cancers remain incurable due to the development of drug resistance, minimal residual disease (MRD) and disease relapse, highlighting an incomplete understanding of the mechanisms underlying these processes. In recent years, the impact of non-genetic factors on neoplastic transformations has increasingly been acknowledged, and growing evidence suggests that low oxygen (O2 ) levels (ie hypoxia) in the tumour microenvironment play a critical role in the development and treatment of cancer. As a result, there is a growing need to develop research tools capable of reproducing physiologically relevant O2 conditions encountered by cancer cells in their natural environments in order to gain in-depth insight into tumour cell metabolism and function. In this review, the authors highlight the importance of hypoxia in the pathogenesis of malignant diseases and provide an overview of novel engineering tools that have the potential to further drive this evolving, yet technically challenging, field of cancer research.

Autonomic Nervous Function in Patients with Sudden Sensorineural Hearing Loss and Its Association with Prognosis and Disease Severity.

INTRODUCTION: Vascular disorder is considered one of the main mechanisms of sudden sensorineural hearing loss (SSNHL) due to the anatomy of the inner ear. One factor that can contribute to vascular disorder is impairment in the autonomic nervous system. This study aims to investigate autonomic function in patients with SSNHL and its association with prognosis and disease severity from January 2018 to October 2019. METHODS: We conducted a cross-sectional study involving 40 healthy controls and 55 subjects with SSNHL. We compared the autonomic function of controls and patients using heart rate variability (HRV). SSNHL patients were divided into improvement and no-improvement groups and into mild and severe groups according to pure-tone audiometry results. RESULTS: The SSNHL group had significantly decreased total power (TP), low frequency (LF), and high frequency (HF) compared to the control group. However, there were no significant differences between the mild and severe groups. In the no-improvement group, LF was significantly higher and normalized HF was significantly lower than in the improvement group. According to a multiple logistic regression analysis, age and LF were significantly correlated with improvement. CONCLUSION: This is the first study to evaluate the significance of HRV in patients with SSNHL, according to prognosis and disease severity. Further studies about the relationship between autonomic nervous system and SSNHL with larger sample size and prospective design are needed.

Ssu72 Dual-Specific Protein Phosphatase: From Gene to Diseases.

More than 70% of eukaryotic proteins are regulated by phosphorylation. However, the mechanism of dephosphorylation that counteracts phosphorylation is less studied. Phosphatases are classified into 104 distinct groups based on substrate-specific features and the sequence homologies in their catalytic domains. Among them, dual-specificity phosphatases (DUSPs) that dephosphorylate both phosphoserine/threonine and phosphotyrosine are important for cellular homeostasis. Ssu72 is a newly studied phosphatase with dual specificity that can dephosphorylate both phosphoserine/threonine and phosphotyrosine. It is important for cell-growth signaling, metabolism, and immune activation. Ssu72 was initially identified as a phosphatase for the Ser5 and Ser7 residues of the C-terminal domain of RNA polymerase II. It prefers the cis configuration of the serine-proline motif within its substrate and regulates Pin1, different from other phosphatases. It has recently been reported that Ssu72 can regulate sister chromatid cohesion and the separation of duplicated chromosomes during the cell cycle. Furthermore, Ssu72 appears to be involved in the regulation of T cell receptor signaling, telomere regulation, and even hepatocyte homeostasis in response to a variety of stress and damage signals. In this review, we aim to summarize various functions of the Ssu72 phosphatase, their implications in diseases, and potential therapeutic indications.

Usage of Natural Volatile Organic Compounds as Biological Modulators of Disease.

Plants produce a wide variety of natural volatile organic compounds (NVOCs), many of which are unique to each species. These compounds serve many purposes, such as fending off herbivores and adapting to changes in temperature and water supply. Interestingly, although NVOCs are synthesized to deter herbivores, many of these compounds have been found to possess several therapeutic qualities, such as promoting nerve stability, enhancing sleep, and suppressing hyperresponsiveness, in addition to acting as antioxidants and anti-inflammatory agents. Therefore, many NVOCs are promising drug candidates for disease treatment and prevention. Given their volatile nature, these compounds can be administered to patients through inhalation, which is often more comfortable and convenient than other administration routes. However, the development of NVOC-based drug candidates requires a careful evaluation of the molecular mechanisms that drive their therapeutic properties to avoid potential adverse effects. Furthermore, even compounds that appear generally safe might have toxic effects depending on their dose, and therefore their toxicological assessment is also critical. In order to enhance the usage of NVOCs this short review focuses not only on the biological activities and therapeutic mode of action of representative NVOCs but also their toxic effects.

Clinical outcomes of primary aldosteronism based on lateralization index and contralateral suppression index after adrenal venous sampling in real-world practice: a retrospective cohort study.

BACKGROUND: We investigated whether the contralateral suppression index in aldosterone-producing adrenal adenoma could be used as a diagnostic criterion when catheterization in either right or left adrenal vein fails or when a discrepancy in the adrenal vein sampling (AVS) results and imaging findings occurs in the real-world practice. METHODS: We retrospectively reviewed 48 patients who had resistant hypertension (HTN) or hypokalemia with a biochemical diagnosis of primary aldosteronism and who underwent AVS from January 2009 to June 2017 at a tertiary referral hospital. Selection index (SI), lateralization index (LI), and contralateral suppression index (CSI) were calculated based on AVS results and the final clinical outcomes were evaluated. RESULTS: The catheterization of both adrenal veins was successful in 43 of 48 (89.6%) patients. The lateralization based only on LI was performed in 23 out of 43 (53.5%) patients. When CSI and LI were combined in decision making, the concordance between adrenal computed tomography scan and AVS for unilateral lesion improved from 59.3% (19/32) to 75.0% (24/32). CSI also correlated well with unilateral adrenal disease in the catheterization failure group. The final outcomes of HTN were better in the contralateral suppression group. CONCLUSION: CSI combined with LI could be a supplementary diagnostic tool in patients with non-lateralization or catheterization failure and predict the clinical outcomes of HTN in patients with primary aldosteronism.

Epidemiology and Seasonal Variation of Ménière's Disease: Data from a Population-Based Study.

INTRODUCTION: Ménière's disease (MD) is a disease of the inner ear. In Asian countries, there is one previous epidemiologic study that used a retrospective survey of a specific district. Previous studies have demonstrated that weather variables are strongly associated with symptom aggravation in MD. However, no study has reported on seasonal variation of MD. METHODS: We conducted a retrospective population-based study using the Korean national health insurance claims database (NHICD). In the present study, the prevalence and incidence of MD from 2013 to 2017 were calculated. Prevalence and incidence of MD according to sex, age group, and monthly incidence are presented. Seasonal incidence was calculated for four seasons. The seasonal average humidity and atmospheric pressure were also calculated. RESULTS: The incidence rate of MD showed a rapid yearly increase from 2013 to 2017 in Korea. The prevalence and incidence rate by age group continued to increase up to the 70 year olds. The female-to-male ratio was 2.17. The seasonal incidence of MD was relatively high in summer and autumn and relatively low in winter and spring; however, there were no significant differences. DISCUSSION/CONCLUSIONS: The rapid progression to an aging society, increase in medical accessibility, and lifestyle changes could be the reasons for the elevation of the incidence rate in the Korean population. Consistent with a previous study, the incidence of MD was higher in seasons with high humidity and low atmospheric pressure; however, there were no significant differences. Further studies about the relationship between diet and MD, seasonality of MD with long-term analysis, and investigating the underlying mechanisms connecting weather and MD are needed.

Successful hyaluronic acid filler injection in a chronic myeloid leukemia patient taking imatinib mesylate.

Dermal fillers are highly favored around the globe as minimally invasive or nonsurgical procedures. Imatinib mesylate is the first-line treatment for patients diagnosed with chronic myeloid leukemia. However, some studies describe that imatinib mesylate may increase the tendency of skin fragility which can lead to easy bruising and hyperpigmentation after invasive skin procedures. Yet, to our knowledge, no studies have described any successful dermal filler injection performed on patients who are under imatinib mesylate treatment. Hence, we present a case successfully treated with hyaluronic acid filler injection on a patient under imatinib mesylate treatment. We carefully propose that hyaluronic acid filler can be an effective means of rejuvenation and cosmetic enhancement for those under imatinib mesylate treatment.

Depressive Symptoms among Former Spousal Caregivers: Comparing Stressors, Resources, and Circumstances of Caregiving Cessation among Older Husbands and Wives.

Little research focuses on the mental health of caregivers (CGs) who stop providing care to their community-dwelling spouse. We examine depressive symptoms of former primary CG spouses who stopped caregiving over a two-year follow-up period when the care recipient (CR): (1) no longer has functional problems; (2) continues having functional problems; or (3) dies. Using data from the Health and Retirement Study (2000-2014), we located 2,370 couples who were both 50+ at baseline and where one partner provided help with ADL and/or IADL limitations but did not do so two years later. OLS regressions stratified by gender indicated that both male and female former spousal CGs whose CR died had significantly more depressive symptoms than those who ceased caregiving when their spouse did or did not still have functional problems. Former wife CGs who were older and whose husbands had more baseline ADLs had fewer follow-up depressive symptoms; wife CGs whose husbands had a nursing home stay had more depressive symptoms. Former husband CGs who had provided longer monthly hours of care had fewer follow-up symptoms. Findings underscore the importance of targeting mental and physical health services to both former caregiving husbands and wives, especially after spousal death.

Design, synthesis and biological evaluation of glutamic acid derivatives as anti-oxidant and anti-inflammatory agents.

A series of glutamic acid derivatives was synthesized and evaluated for their antioxidant activity and stability. We found several potent and stable glutamic acid derivatives. Among them, compound 12b exhibited good in vitro activity, chemical stability and cytotoxicity. A prototype compound 12b showed an anti-inflammatory effect in LPS-stimulated RAW 264.7 cell lines and in a zebrafish model.

Optimizing acupuncture treatment for dry eye syndrome: a systematic review.

BACKGROUND: In a former meta-analysis review, acupuncture was considered a potentially effective treatment for dry eye syndrome (DES), but there were heterogeneities among the outcomes. We updated the meta-analysis and conducted subgroup analysis to reduce the heterogeneity and suggest the most effective acupuncture method based on clinical trials. METHODS: We searched for randomized controlled trials (RCTs) in 10 databases (MEDLINE, EMBASE, CENTAL, AMED, SCOPUS, CNKI, Wangfang database, Oriental Medicine Advanced Searching Integrated System (OASIS), Koreamed, J-stage) and searched by hand to compare the effects of acupuncture and artificial tears (AT). We also conducted subgroup analysis by (1) method of intervention (acupuncture only or acupuncture plus AT), (2) intervention frequency (less than 3 times a week or more than 3 times a week), (3) period of treatment (less than 4 weeks or more than 4 weeks), and (4) acupoints (BL1, BL2, ST1, ST2, TE23, Ex-HN5). The Bucher method was used for subgroup comparisons. RESULTS: Nineteen studies with 1126 patients were included. Significant improvements on the Schirmer test (weighted mean difference[WMD], 2.14; 95% confidence interval[CI], 0.93 to 3.34; p = 0.0005) and break up time (BUT) (WMD, 0.98; 95% CI, 0.79 to 1.18; p < 0.00001) were reported. In the subgroup analysis, acupuncture plus AT treatment had a weaker effect in BUT but a stronger effect on the Schirmer test and a better overall effect than acupuncture alone. For treatment duration, treatment longer than 1 month was more effective than shorter treatment. With regard to treatment frequency, treatment less than three times a week was more effective than more frequent treatment. In the acupoint analysis, acupuncture treatment including the BL2 and ST1 acupoints was less effective than treatment that did not include them. None of those factors reduced the heterogeneity. CONCLUSIONS: Acupuncture was more effective than AT in treating DES but showed high heterogeneity. Intervention differences did not influence the heterogeneity.