Direct Synthesis of C4-Acyl Indoles via C-H Acylation.

The direct synthesis of C4-acyl indoles deprived of C2 and C3 substituents has proven to be challenging, with scarce efficient synthetic routes being reported. Herein, we disclose a highly site-selective palladium-catalyzed C-H acylation for the construction of C4-acyl indoles via a Catellani-Lautens cyclization strategy. In addition, we systematically studied the ortho C-H acylation mechanism of iodoaniline through density functional theory (DFT) calculations and combined experimental results to elucidate the principle of high chemoselectivity brought by triazine benzoate as an acylation reagent.

Factors and Their Impact on Treatment Effect of Acupuncture in Different Outcomes: A Meta-Regression of Acupuncture Randomized Controlled Trials / 中国结合医学杂志

BACKGROUND@#The effects of acupuncture have varied in different randomized controlled trials (RCTs), and there are many factors that influence treatment effect of acupuncture in different outcomes, with conflicting results.@*OBJECTIVE@#To identify factors and their impact on the treatment effect of acupuncture in different outcomes.@*METHODS@#Acupuncture RCTs were searched from 7 databases including Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc between January 1st, 2015 and December 31st, 2019. Eligible studies must compare acupuncture to no acupuncture, sham acupuncture, or waiting lists, and report at least 1 patient-important outcome. A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables, even those excluded from the multivariable model due to collinearities. We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences (SMDs), categorising them as small (<0.2), moderate (0.2-0.4), or large (>0.4) effects.@*RESULTS@#The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables. High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude, the difference of adjusted SMDs 0.46, 95% confidence interval (CI) 0.07 to 0.84; P=0.02]. The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables. Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture (0.30, 95% CI 0.06 to 0.53; P=0.01). The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables. Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects, compared to non-penetrating acupuncture and fixed regimen, respectively (0.40, 95% CI 0 to 0.80; P=0.05; 0.29, 95% CI 0.06 to 0.53; P=0.01).@*CONCLUSIONS@#High-frequency acupuncture sessions appear to be a more effective approach to managing painful symptoms. Penetrating acupuncture demonstrated greater effect in relieving non-painful symptoms. Both penetrating acupuncture type and flexible acupuncture regimen were linked to significant treatment effects in function outcomes. Future studies should consider the factors that are significantly associated with the effects of acupuncture in patient-important outcomes.

Finite element analysis of cervical intervertebral discs after removing different ranges of uncinate processes / 解剖学报

Objective To study the stress change characteristics of the cervical disc after removing different ranges of the uncinate process by establishing a three⁃dimensional finite element model of the C

Association between sedentary behaviors with cardiorespiratory fitness and executive function among adolescents / 中国学校卫生

Objective@#To explore the relationship between sedentary behavior with cardiorespiratory fitness and executive function in adolescents, and to provide some references for sedentary behavior prevention and executive function improvement.@*Methods@#From September to December 2022, a total of 5 018 adolescents aged 13 to 18 years were selected by stratified random sampling method in Shanghai, Suzhou, Taiyuan,Wuyuan, Xingyi, and Urumqi to conduct physical activity survey, as well as cardiorespiratory fitness and executive function assessment. Pearson s correlation was used to analyze the relationship between sedentary behavior, cardiorespiratory fitness and executive function. The mediation effect model was fitted by the bootstrap mediation procedure in the PROCESS (version 3.3 ) SPSS macro compiled by Haves, and the mediation effect of adolescents cardiorespiratory fitness in the relationship between static behavior and executive function was examined using model 4 in the PROCESS SPSS macro, where Boosrap method was used to compute the mediation effect of adolescents cardiorespiratory fitness. where the Boosrap method was used to calculate confidence intervals for the mediating effects.@*Results@#Adolescents daily sedentary time was positively correlated with both the refreshing function (1-back and 2-back) and the switch function reaction time ( r =0.05, 0.07, 0.05, P <0.01). Adolescent VO 2max was negatively correlated with both the refreshing function (1-back,2-back) and the switching function ( r =-0.09, -0.14 , -0.11, P <0.01). Adolescents daily sedentary time was negatively correlated with VO 2max ( r =-0.04, P <0.01); cardiorespiratory fitness mediated effect values between sedentary behavior and refreshing function (1-back and 2-back) and converted function were 0.20(95% CI =0.06-0.36), 0.43(95% CI =0.14-0.74) and 0.13 (95% CI =0.04-0.22), with mediating effect shares of 6.87%, 8.33% and 8.59%, respectively.@*Conclusion@#The duration of sedentary behavior in adolescents is related to executive function performance, and cardiorespiratory fitness may serve as a mediator to mediate the association between sedentary behavior and executive function in adolescents.

Deep Learning-Driven Library Design for the De Novo Discovery of Bioactive Thiopeptides.

Broad substrate tolerance of ribosomally synthesized and post-translationally modified peptide (RiPP) biosynthetic enzymes has allowed numerous strategies for RiPP engineering. However, despite relaxed specificities, exact substrate preferences of RiPP enzymes are often difficult to pinpoint. Thus, when designing combinatorial libraries of RiPP precursors, balancing the compound diversity with the substrate fitness can be challenging. Here, we employed a deep learning model to streamline the design of mRNA display libraries. Using an in vitro reconstituted thiopeptide biosynthesis platform, we performed mRNA display-based profiling of substrate fitness for the biosynthetic pathway involving five enzymes to train an accurate deep learning model. We then utilized the model to design optimal mRNA libraries and demonstrated their utility in affinity selections against IRAK4 kinase and the TLR10 cell surface receptor. The selections led to the discovery of potent thiopeptide ligands against both target proteins (KD up to 1.3 nM for the best compound against IRAK4 and 300 nM for TLR10). The IRAK4-targeting compounds also inhibited the kinase at single-digit µM concentrations in vitro, exhibited efficient internalization into HEK293H cells, and suppressed NF-kB-mediated signaling in cells. Altogether, the developed approach streamlines the discovery of pseudonatural RiPPs with de novo designed biological activities and favorable pharmacological properties.

Infection of sheep by Echinococcus multilocularis in Gansu, China: evidence from mitochondrial and nuclear DNA analysis.

BACKGROUND: In the normal life cycle of the parasite (Echinococcus multilocularis) that causes alveolar echinococcosis, domestic and wild carnivores act as definitive hosts, and rodents act as intermediate hosts. The presented study contributes to the research on the distribution and transmission pattern of E. multilocularis in China having identified sheep as an unusual intermediate host taking part in the domestic transmission of alveolar echinococcosis in Gansu Province, China. METHODS: From 2020 to 2021, nine whitish different cyst-like were collected from the liver of sheep in Gansu Province for examination. A near complete mitochondrial (mt) genome and selected nuclear genes were amplified from the cyst-like lesion for identification. To confirm the status of the specimen, comparative analysis with reference sequences, phylogenetic analysis, and network analysis were performed. RESULTS: The isolates displayed ≥ 98.87% similarity to E. multilocularis NADH dehydrogenase sub-unit 1 (nad1) (894 bp) reference sequences deposited in GenBank. Furthermore, amplification of the nad4 and nad2 genes also confirmed all nine samples as E. multilocularis with > 99.30% similarity. Additionally, three nuclear genes, pepck (1545 bp), elp-exons VII and VIII (566 bp), and elp-exon IX (256 bp), were successfully amplified and sequenced for one of the isolates with 98.42% similarity, confirming the isolates were correctly identified as E. multilocularis. Network analysis also correctly placed the isolates with other E. multilocularis. CONCLUSIONS: As a result of the discovery of E. multilocularis in an unusual intermediate host, which is considered to have the highest zoonotic potential, the result clearly demonstrated the necessity for expanded surveillance in the area.

Safety and immunogenicity of heterologous boosting with orally aerosolised or intramuscular Ad5-nCoV vaccine and homologous boosting with inactivated vaccines (BBIBP-CorV or CoronaVac) in children and adolescents: a randomised, open-label, parallel-controlled, non-inferiority, single-centre study.

BACKGROUND: Heterologous booster immunisation with orally administered aerosolised Ad5-nCoV vaccine (AAd5) has been shown to be safe and highly immunogenic in adults. Here, we aimed to assess the safety and immunogenicity of heterologous booster immunisation with orally administered AAd5 in children and adolescents aged 6-17 years who had received two doses of inactivated vaccine (BBIBP-CorV or CoronaVac). METHODS: We did a randomised, open-label, parallel-controlled, non-inferiority study to assess the safety and immunogenicity of heterologous booster immunisation with AAd5 (0·1 mL) or intramuscular Ad5-nCoV vaccine (IMAd5; 0·3 mL) and homologous booster immunisation with inactivated vaccine (BBIBP-CorV or CoronaVac; 0·5 mL) in children (aged 6-12 years) and adolescents (aged 13-17 years) who had received two doses of inactivated vaccine at least 3 months earlier in Hunan, China. Children and adolescents who were previously immunised with two-dose BBIBP-CorV or CoronaVac were recruited for eligibility screening at least 3 months after the second dose. A stratified block method was used for randomisation, and participants were stratified by age and randomly assigned (3:1:1) to receive AAd5, IMAd5, or inactivated vaccine. The study staff and participants were not masked to treatment allocation. Laboratory and statistical staff were masked during the study. In this interim analysis, adverse events within 14 days and geometric mean titre (GMT) of serum neutralising antibodies on day 28 after the booster vaccination, based on the per-protocol population, were used as the primary outcomes. The analysis of non-inferiority was based on comparison using a one-sided 97·5% CI with a non-inferiority margin of 0·67. This study was registered at ClinicalTrials.gov, NCT05330871, and is ongoing. FINDINGS: Between April 17 and May 28, 2022, 436 participants were screened and 360 were enrolled: 220 received AAd5, 70 received IMAd5, and 70 received inactivated vaccine. Within 14 days after booster vaccination, vaccine-related adverse reactions were reported: 35 adverse events (in 13 [12%] of 110 children and 22 [20%] of 110 adolescents) in 220 individuals in the AAd5 group, 35 (in 18 [51%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 13 (in five [14%] of 35 children and eight [23%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. Solicited adverse reactions were also reported: 34 (13 [12%] of 110 children and 21 [10%] of 110 adolescents) in 220 individuals in the AAd5 group, 34 (17 [49%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 12 (five [14%] of 35 children and seven [20%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. The GMTs of neutralising antibodies against ancestral SARS-CoV-2 Wuhan-Hu-1 (Pango lineage B) in the AAd5 group were significantly higher than the GMTs in the inactivated vaccine group (adjusted GMT ratio 10·2 [95% CI 8·0-13·1]; p<0·0001). INTERPRETATION: Our study shows that a heterologous booster with AAd5 is safe and highly immunogenic against ancestral SARS-CoV-2 Wuhan-Hu-1 in children and adolescents. FUNDING: National Key R&D Program of China.

Allantoin induces pruritus by activating MrgprD in chronic kidney disease.

Chronic kidney disease (CKD) is a disease with decreased, irreversible renal function. Pruritus is the most common skin symptom in patients with CKD, especially in end-stage renal disease. The underlying molecular and neural mechanism of CKD-associated pruritus (CKD-aP) remains obscure. Our data show that the level of allantoin increases in the serum of CKD-aP and CKD model mice. Allantoin could induce scratching behavior in mice and active DRG neurons. The calcium influx and action potential reduced significantly in DRG neurons of MrgprD KO or TRPV1 KO mice. U73122, an antagonist of phospholipase C, could also block calcium influx in DRG neurons induced by allantoin. Thus, our results concluded that allantoin plays an important role in CKD-aP, mediated by MrgprD and TrpV1, in CKD patients.

Modifiable Risk Factor Score and Fecundability in a Preconception Cohort in Singapore.

Importance: Although multiple modifiable risk factors have been identified for reduced fecundability (defined as lower probability of conception within a menstrual cycle), no scoring system has been established to systematically evaluate fecundability among females who are attempting to conceive. Objective: To examine the association of a risk score based on 6 modifiable factors with fecundability, and to estimate the percentage reduction in incidence of nonconception if all study participants achieved a minimal risk score level. Design, Setting, and Participants: This population-based cohort study obtained data from the S-PRESTO (Singapore Preconception Study of Long-Term Maternal and Child Outcomes) prospective cohort study. Females of reproductive age who were trying to conceive were enrolled from February 2015 to October 2017 and followed for 1 year, ending in November 2018. Data were analyzed from March to May 2022. Exposures: A reduced fecundability risk score was derived by giving participants 1 point for each of the following factors: unhealthy body mass index, unhealthy diet, smoking, alcohol intake, folic acid supplement nonuser, and older maternal age. Total scores ranged from 0 to 6 and were classified into 5 levels: level 1 (score of 0 or 1), level 2 (score of 2), level 3 (score of 3), level 4 (score of 4), and level 5 (score of 5 or 6). Main Outcomes and Measures: Fecundability, measured by time to conception in cycles, was analyzed using discrete-time proportional hazards models with confounder adjustment. Results: A total of 937 females (mean [SD] age, 30.8 [3.8] years) were included, among whom 401 (42.8%) spontaneously conceived within 1 year of attempting conception; the median (IQR) number of cycles before conception was 4 (2-7). Compared with participants with a level 1 risk score, those with level 2, 3, 4, and 5 risk scores had reductions in fecundability of 31% (adjusted fecundability ratio [FR], 0.69; 95% CI, 0.54-0.88), 41% (FR, 0.59; 95% CI, 0.45-0.78), 54% (FR, 0.46; 95% CI, 0.31-0.69) and 77% (FR, 0.23; 95% CI, 0.07-0.73), respectively. Assessment of the population attributable fraction showed that all participants achieving a minimal (level 1) risk level would be associated with a reduction of 34% (95% CI, 30%-39%) in nonconception within a year. Conclusions and Relevance: Results of this study revealed the co-occurrence of multiple modifiable risk factors for lowered fecundability and a substantially higher conception rate among participants with no or minimal risk factors. The risk assessment scoring system proposed is a simple and potentially useful public health tool for mitigating risks and guiding those who are trying to conceive.

Impact of assisted reproductive technology on birth weight discordance in twins / 中国当代儿科杂志

OBJECTIVES@#To explore the association between assisted reproductive technology (ART) and birth weight discordance in twins (BWDT).@*METHODS@#A retrospective analysis was conducted on twin infants born between January 2011 and December 2020 at the Third Affiliated Hospital of Guangzhou Medical University, with complete basic birth data. The impact of ART on the occurrence of BWDT was identified by the multivariate logistic regression analysis.@*RESULTS@#A total of 3 974 pairs of twins were included, with 1 431 conceived naturally and 2 543 through ART. Neonates in the ART group had higher birth weights than those in the naturally conceived group (P<0.001). The incidence of BWDT was lower in the ART group compared to the naturally conceived group (16.17% vs 21.09%, P<0.001). The multivariate logistic regression analysis, adjusting for confounding factors such as maternal age, parity, pre-pregnancy body mass index, gestational diabetes, hypothyroidism, gestational age, and chorionic properties, showed no significant difference in the risk of BWDT between the ART and naturally conceived groups (P>0.05).@*CONCLUSIONS@#ART is not associated with the risk of BWDT.

Application of femoral I.D.E.A.L localization in anterior cruciate ligament reconstruction with single bundle anterior cruciate ligament / 中国骨伤

OBJECTIVE@#To evaluate the effect of femoral I.D.E.A.L localization in single bundle anterior cruciate ligament reconstruction (ACLR).@*METHODS@#From January 2019 to October 2022, 122 patients with anterior cruciate ligament injury were treated with ACLR, including 83 males and 39 females. The age ranged from 23 to 43 years old, with an average of (32.19 ±8.55) years old. The course of disease ranged from 1 week to 6 months. According to the different surgical schemes, the patients were divided into two groups, namely the traditional group, which adopted the over-the-top femoral lateral positioning scheme, including 64 patients. The I.D.E.A.L group adopted the I.D.E.A.L femoral lateral positioning scheme, including 58 patients. The patient has pain and dysfunction of knee joint before operation. MRI of knee joint indicates anterior cruciate ligament injury. The visual analogue scale(VAS), International Knee Documentation Committee(IKDC) scoring system and Lysholm scoring system were used to evaluate the knee joint function of the patient. KT-2000 was used to detect the recovery of knee joint after operation and to count the postoperative complications.@*RESULTS@#The wounds healed well after operation. One hundred and twenty-tow patients were followed up for 15 to 46 months, with an average of (25.45±9.22) months. The knee joint stability of patients after operation was significantly increased. The VAS at 1 day and 1 week after operation of patients in the I.D.E.A.L group was significantly lower than that in the traditional group(P<0.05). The IKDC score and Lysholm score of patients in the I.D.E.A.L group were significantly higher than those in the traditional group(P<0.05). In the traditional group, there were 6 cases of short-term (<1 month) complications and 19 cases of long-term (≥1 month)complicatios. In the I.D.E.A.L group, there were 3 cases of short-term complications and 7cases of long-term complications(P<0.05).@*CONCLUSION@#The single bundle anterior cruciate ligament reconstruction and femoral I.D.E.A.L positioning can achieve better early postoperative effect and reduce early postoperative pain.

Scoping review of acupuncture-moxibustion treatment for non-specific low back pain / 中国中药杂志

This study systematically searched and sorted out randomized controlled trial(RCT) of acupuncture-moxibustion treatment for non-specific low back pain by scoping review, so as to demonstrate the current state of the research evidence and provide a reference point for future clinical research and healthcare decision-making. Eight commonly used Chinese and English databases were searched, and the search time was from the establishment of the databases to July 7, 2023, so as to analyze the characteristics of the current status of the current research through visualization methods. A total of 50 studies were included, including 23 studies in Chinese and 27 studies in English. The overall number of studies showed an increasing trend. The percentage of studies published in Chinese non-core journals was 42.0%. The disease subtypes of interest were mainly chronic non-specific low back pain, accounting for 68.0% of the studies. The sample sizes of the studies were mainly concentrated in the range of 50-100 cases. A total of 15 types of interventions were categorized, with acupuncture interventions being the most studied. Duration of treatment did not exceed one month in 80.0% of the studies. Only 8.0% of the studies used minimal clinical important difference(MCID) as a basis for judgment. The follow-up period was set within 3 months in 28.0% of the studies, and 82.0% of the studies concluded that acupuncture-moxibustion was effective in the treatment of non-specific lower back pain. Adverse events were reported in 20.0% of the studies. The risk of bias in the included studies was dominated by low risk of bias and uncertain risk of bias, with fewer studies focusing on high risks of bias. In most of the studies, acupuncture-moxibustion was significantly more effective than the control group. The research on acupuncture-moxibustion treatment for non-specific low back pain is developing rapidly, but there are still insufficient studies on psychological state, safety, and other indicators, and there are still some studies with uncertain risks of bias, which is not conducive to the generalization and application of the findings. Therefore, future studies should improve and refine these shortcomings.

Fidelity in acupuncture-moxibustion clinical research: application and reflection / 中国针灸

As an indicator that measures the degree of implementation of intervention measures during the implementation process, fidelity could be used for monitoring and quality evaluation of the completion degree of intervention measures, and plays an important role in improving the degree of intervention implementation and clarifying the factors that affect intervention implementation. This article aims to introduce the connotation and significance, measurement, control, and current application status of fidelity, as well as the current application status of fidelity in acupuncture-moxibustion clinical research and its inspiration for future research. Meanwhile, based on the existing evaluation tool development methods of fidelity and the characteristics of acupuncture-moxibustion clinical research, a preliminary fidelity evaluation framework is proposed. Introducing fidelity into acupuncture-moxibustion clinical research could improve the implementation quality and compliance of acupuncture-moxibustion in clinical research, increase the credibility and effectiveness of clinical research results, and promote the transformation of acupuncture-moxibustion experience into easily learnable and promotable treatment plans.

Evaluation of the report quality of Chinese and English randomized controlled trials of acupuncture based on CONSORT statement and STRICTA checklist / 中国针灸

OBJECTIVE@#To evaluate the report quality of Chinese and English randomized controlled trials (RCTs) of acupuncture based on the CONSORT statement and STRICTA checklist.@*METHODS@#The Chinese and English RCTs of acupuncture published from January 1, 2015 to December 31, 2019 were searched in 7 databases including PubMed. The report quality of the included RCTs was evaluated with the CONSORT 2010 statement and STRICTA checklist.@*RESULTS@#A total of 506 Chinese RCTs and 76 English RCTs were included. According to the CONSORT statement, in Chinese RCTs, the items with report rate less than 50% accounted for 78.38% of all items, and the report rate of 25 items, such as background and reason, study design, outcome index, and sample size, was less than 10%. In English RCTs, the items with report rate less than 50% accounted for 35.14% of all items, and 5 items had a report rate of less than 10%. The difference of the report rate of 15 items, such as background, reason and study design, was more than 50% between Chinese and English RCTs. The report rate of all items of STRICTA checklist was relatively high in both Chinese and English RCTs. In Chinese RCTs, the items with report rate less than 50% accounted for 29.41% of all items, which included acupuncture rationale and depth of insertion. In English RCTs, only two items had a report rate less than 50%, which were acupuncture rationale, setting and context of treatment. The report rate of five items, including needle retention time, frequency and duration of treatment sessions, details of other interventions administered to the acupuncture group, setting and context of treatment, and precise description of the control or comparator in Chinese RCTs, were higher than in English RCTs.@*CONCLUSION@#The report quality of Chinese acupuncture RCT needs to be improved urgently, and corresponding measures should be taken to further standardize the writing and reporting of acupuncture clinical research.

Prevalence of chronic kidney disease and its association with lifestyle factors in adults from 10 regions of China / 中华流行病学杂志

Objective: To investigate the distribution of chronic kidney disease (CKD) in participants from the China Kadoorie Biobank (CKB) study and evaluate the association between lifestyle risk factors and CKD. Methods: Based on the baseline survey data and follow-up data (as of December 31, 2018) of the CKB study, the differences in CKD cases' area and population distributions were described. Cox proportional hazards regression model was used to estimate the association between lifestyle risk factors and the risk of CKD. Results: A total of 505 147 participants, 4 920 cases of CKD were recorded in 11.26 year follow up with a incidence rate of 83.43/100 000 person-years. Glomerulonephropathy was the most common type. The incidence of CKD was higher in the urban area, men, and the elderly aged 60 years and above (87.83/100 000 person-years, 86.37/100 000 person-years, and 132.06/100 000 person-years). Current male smokers had an increased risk for CKD compared with non-smokers or occasional smokers (HR=1.18, 95%CI: 1.05-1.31). The non-obese population was used as a control group, both general obesity determined by BMI (HR=1.19, 95%CI: 1.10-1.29) and central obesity determined by waist circumference (HR=1.27, 95%CI: 1.19-1.35) were associated with higher risk for CKD. Conclusion: The risks for CKD varied with area and population in the CKB cohort study, and the risk was influenced by multiple lifestyle factors.

Tea consumption and cancer: a Mendelian randomization study / 中华流行病学杂志

Objective: A Mendelian randomization (MR) analysis was performed to assess the relationship between tea consumption and cancer. Methods: There were 100 639 participants with the information of gene sequencing of whole genome in the China Kadoorie Biobank. After excluding those with cancer at baseline survey, a total of 100 218 participants were included in this study. The baseline information about tea consumption were analyzed, including daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption. We used the two-stage least square method to evaluate the associations between three tea consumption variables and incidence of cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer. Multivariable MR and analysis only among nondrinkers were used to control the impact of alcohol consumption. Sensitivity analyses were also performed, including inverse variance weighting, weighted median, and MR-Egger. Results: We used 54, 42, and 28 SNPs to construct non-weighted genetic risk scores as instrumental variables for daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption, respectively. During an average of (11.4±3.0) years of follow-up, 6 886 cases of cancer were recorded. After adjusting for age, age2, sex, region, array type, and the first 12 genetic principal components, there were no significant associations of three tea consumption variables with the incidence of cancer and cancer subtypes. Compared with non-daily tea drinkers, the HR (95%CI) of daily tea drinkers for cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer, are respectively 0.99 (0.78-1.26), 1.17 (0.58-2.36), 0.86 (0.40-1.84), 0.85 (0.42-1.73), 1.39 (0.85-2.26) and 0.63 (0.28-1.38). After controlling the impact of alcohol consumption and performing multiple sensitivity analyses, the results were similar. Conclusion: There is no causal relationship between tea consumption and risk of cancer in population in China.