Objective To explore whether there is a causal relationship between intestinal flora and esophageal cancer. Methods Summary statistics of intestinal flora and esophageal cancer were obtained from the Genome-wide Association Studies (GWAS) database. Five methods, including inverse variance weighted (IVW), weighted median estimation, Mendelian randomization (MR)-Egger regression, single mode, and weighted mode, were used for analysis, with IVW as the main analysis method. Sensitivity analysis was used to evaluate the reliability of MR results. Results In the IVW method, Oxalobacteraceae [OR=1.001, 95%CI (1.000, 1.002), P=0.023], Faecalibacterium [OR=1.001, 95%CI (1.000, 1.002), P=0.028], Senegalimassilia [OR=1.002, 95%CI (1.000, 1.003), P=0.006] and Veillonella [OR=1.001, 95%CI (1.000, 1.002), P=0.018] were positively correlated with esophageal cancer, while Burkholderiales [OR=0.999, 95%CI (0.998, 1.000), P=0.002], Eubacterium oxidoreducens [OR=0.998, 95%CI (0.997, 0.999), P=0.038], Romboutsia [OR=0.999, 95%CI (0.998, 1.000), P=0.048] and Turicibacter [OR=0.998, 95%CI (0.997, 0.999), P=0.013] were negatively correlated with esophageal cancer. Sensitivity analysis showed no evidence of heterogeneity, horizontal pleiotropy and reverse causality. Conclusion Oxalobacteraceae, Faecalibacterium, Senegalimassilia and Veillonella increase the risk of esophageal cancer, while Burkholderiales, Eubacterium oxidoreducens, Romboutsia and Turicibacter decrease the risk of esophageal cancer. Further studies are needed to explore how these bacteria affect the progression of esophageal cancer.

Objective To provide experimental evidence for selecting acupuncture timing in clinical practice,the optimal time for enhancing the brain effects of electroacupuncture at the Hegu acupoint(LI4)by observing brain imaging data,hemodynamic changes and differences in brain functional connectivity across the twelve traditional Chinese time periods were determined.Methods Thirty-six C57BL/6 mice were randomly divided into 12 groups corresponding to each of the twelve time periods(Zi,Chou,Yin,Mao,Chen,Si,Wu,Wei,Shen,You,Xu,Hai),with 3 mice per group.Each mouse received electroacupuncture stimulation using the same protocol.Brain imaging data and dynamic hemodynamic changes were collected using functional ultrasound imaging(FUS)ultrasound imaging technology every 0.4 s over a total duration of 420 s,covering pre-acupuncture(resting state),during acupuncture(task state),and post-acupuncture(post-task state)phases.The hippocampal region(HIP)was used as the observation point to analyze changes in functional connectivity between HIP and other brain regions before and after acupuncture.Results Compared to other time periods,the Mao group exhibited the largest whole-brain activation area and the highest average activation signal intensity.The hemodynamic signal increase in the hippocampal region was more pronounced,and the post-acupuncture blood flow signal intensity remained significantly higher than the pre-acupuncture resting state.Functional connectivity data revealed that,using 0.2 as the standard value,the Mao group showed the greatest number of altered brain regions before and after acupuncture.Notably,only in the Mao group was there a significant enhancement in connectivity between the bilateral hippocampal regions.Conclusion The immediate effects of electroacupuncture at the Hegu acupoint(LI4)and brain functional connectivity vary significantly across different time periods,aligning with the traditional Chinese medicine theory of meridian qi and blood flow.Mao time is identified as the optimal period.

Objective Observe the impact of Qang Gu Kang Wei extraction(KW)on skeletal muscle atrophy in simulated weightlessness rats by regulating endoplasmic reticulum stress and mitochondrial fusion.Methods SD rats were randomy divided the control group(Control),the simulated weightlessness group(TS),and the KW group(TS+KW).Rats were treated with KW with or without tail suspension(TS)for 28 days,and the cross-sectional areas of the gastrocnemius muscle were compared with a control group.The expression levels of endoplasmic reticulum stress(ERS)and key proteins involved in mitochondrial fusion were also analyzed.Results KW treatment reduced the loss of muscle cross-sectional area caused by TS.TS increased the protein expression of glucose-regulated Protein 78(GRP78)and components of the ERS signaling pathways,while KW treatment reduced this increase.TS also inhibited the expression of mitofusin 2(MFN2),which was increased by KW treatment.Additionally,KW treatment promoted the interaction between GRP78 and the endoplasmic reticulum protein sigma-1 receptor(Sig-1R).Conclusion KW may attenuate muscle atrophy caused by simulated weightlessness by regulating ERS and mitochondrial fusion fusion.

Objective To provide experimental evidence for selecting acupuncture timing in clinical practice,the optimal time for enhancing the brain effects of electroacupuncture at the Hegu acupoint(LI4)by observing brain imaging data,hemodynamic changes and differences in brain functional connectivity across the twelve traditional Chinese time periods were determined.Methods Thirty-six C57BL/6 mice were randomly divided into 12 groups corresponding to each of the twelve time periods(Zi,Chou,Yin,Mao,Chen,Si,Wu,Wei,Shen,You,Xu,Hai),with 3 mice per group.Each mouse received electroacupuncture stimulation using the same protocol.Brain imaging data and dynamic hemodynamic changes were collected using functional ultrasound imaging(FUS)ultrasound imaging technology every 0.4 s over a total duration of 420 s,covering pre-acupuncture(resting state),during acupuncture(task state),and post-acupuncture(post-task state)phases.The hippocampal region(HIP)was used as the observation point to analyze changes in functional connectivity between HIP and other brain regions before and after acupuncture.Results Compared to other time periods,the Mao group exhibited the largest whole-brain activation area and the highest average activation signal intensity.The hemodynamic signal increase in the hippocampal region was more pronounced,and the post-acupuncture blood flow signal intensity remained significantly higher than the pre-acupuncture resting state.Functional connectivity data revealed that,using 0.2 as the standard value,the Mao group showed the greatest number of altered brain regions before and after acupuncture.Notably,only in the Mao group was there a significant enhancement in connectivity between the bilateral hippocampal regions.Conclusion The immediate effects of electroacupuncture at the Hegu acupoint(LI4)and brain functional connectivity vary significantly across different time periods,aligning with the traditional Chinese medicine theory of meridian qi and blood flow.Mao time is identified as the optimal period.

Objective To study the influence of implant depth and scanning rod lengths on the accuracy of digital impression for single-tooth implant restoration of the mandibular posterior teeth.Methods Five standard dental cast models with missing right mandibular first molar(46)were prepared with the subgingival implant depths of 0,1,3,5 and 7 mm.ITI RC and ITI RC H11 scanning rods were connected to the replacement body and placed into the seating tract for scanning.The reference data were obtained using a 3D dental scanner,and the experimental data were obtained by 10 scans of each model using a digitized intraoral scanner.Geomagic Wrap 2021 was used to analyze the model data to test the trueness and precision of the models.Results The trueness did not differ significantly among the groups(P>0.05).The implant depth of 1 mm achieved the highest impression precision(66.81±2.45 μm),and the depth of 0 mm resulted in a significantly lower precision(95.60±3.04 μm)than the depth of 1 and 3 mm.Starting from the subgingival depth of 1 mm,the precision of the scan decreased progressively with the increase of the implant depth.At the subgingival implant depth of 5 or 7 mm,the use of an extended rod significantly improved the scan precision.Conclusion For single-tooth implant restoration of the mandibular posterior teeth,the implant depth can substantially affect the accuracy of digital impression,which decreases as the implant depth increases.For a deep implant,the use of a longer scanning rod can improve the scanning accuracy.

Standardized reporting is a crucial factor affecting the use of patient guidelines （PGs）， particularly in the reporting and presentation of recommendations. This paper introduced the current status of PG reporting， including the research on PG content and presentation formats， and provided comprehensive recommendations for PG reporting from aspects such as overall framework， recommendations， presentation format， and readability. First， the presentation of PG recommendations should include clearly defined clinical questions， recommendations and their rationale， and guidance on how patients should implement the interventions； for specific content in the PG， such as level of evidence， level of recommendation， it is recommended to explain in text the reasons for giving different levels of recommendation， i.e.， to present the logic behind giving the level of recommendation to the patient； additional information needed in the recommendation framework should be supplemented by tracing references or authoritative textbooks and literature that support the recommendations. Subsequently， the PG text should be written based on the Reporting Checklist for Public Versions of Guidelines （RIGHT-PVG） reporting framework. Finally， to enhance readability and comprehension， it is recommended to refer to the Patient Education Materials Assessment Tool （PEMAT） for translating PG content. To enhance the readability of PGs， it is suggested to present the PG content in a persona-lized and layered manner.

Since the concept of patient versions of guidelines （PVGs） was introduced into China， several PVGs have been published in China， but we found that there is a big difference between the concept of PVG at home and abroad， and the reason for this difference has not been reasonably explained， which has led to ambiguity and even misapplication of the PVG concept by guideline developers. By analyzing the background and purpose of PVGs， and the understanding of the PVG concept by domestic scholars， we proposed the term patient guidelines （PGs）. This refers to guidelines developed under the principles of evidence-based medicine， centered on health issues that concern patients， and based on the best available evidence， intended for patient use. Except for the general attribute of providing information or education， which is typical of common health education materials， PGs also provide recommendations and assist in decision-making， so PGs include both the patient versions of guidelines （PVG） as defined by the Guidelines International Network （GIN） and "patient-directed guidelines"， i.e. clinical practice guidelines resulting from the adaptation or reformulation of recommendations through clinical practice guidelines.

At present， the process and methodology of patient guidelines （PGs） development varies greatly and lacks systematic and standardised guidance. In addition to the interviews with PG developers， we have sorted out the relevant methodology for the adaptation and development of existing clinical practice guideline recommendations and facilitated expert deliberations to achieve a consensus， so as to finally put forward a proposal for guidance on the process and methodology for the development of PGs. The development of PGs can be divided into the preparation stage， the construction stage， and the completion stage in general， but the specific steps vary according to the different modes of development of PGs. The development process of Model 1 is basically the same as the patient version of the guideline development process provided by the International Guidelines Network， i.e.， team formation， screening of recommendations， guideline drafing， user testing and feedback， approval and dissemination. The developer should also first determine the need for and scope of translating the clinical practice guideline into a patient version during the preparation phase. Model 2 adds user experience and feedback to the conventional clinical practice guideline development process （forming a team， determining the scope of the PG， searching， evaluating and integrating evidence， forming recommendations， writing the guideline， and expert review）. Based on the different models， we sort out the process and methods of PG development and introduce the specific methods of PG development， including how to identify the clinical problem and how to form recommendations based on the existing clinical practice guidelines， with a view to providing reference for guideline developers and related researchers.

Objective To study the influence of implant depth and scanning rod lengths on the accuracy of digital impression for single-tooth implant restoration of the mandibular posterior teeth.Methods Five standard dental cast models with missing right mandibular first molar(46)were prepared with the subgingival implant depths of 0,1,3,5 and 7 mm.ITI RC and ITI RC H11 scanning rods were connected to the replacement body and placed into the seating tract for scanning.The reference data were obtained using a 3D dental scanner,and the experimental data were obtained by 10 scans of each model using a digitized intraoral scanner.Geomagic Wrap 2021 was used to analyze the model data to test the trueness and precision of the models.Results The trueness did not differ significantly among the groups(P>0.05).The implant depth of 1 mm achieved the highest impression precision(66.81±2.45 μm),and the depth of 0 mm resulted in a significantly lower precision(95.60±3.04 μm)than the depth of 1 and 3 mm.Starting from the subgingival depth of 1 mm,the precision of the scan decreased progressively with the increase of the implant depth.At the subgingival implant depth of 5 or 7 mm,the use of an extended rod significantly improved the scan precision.Conclusion For single-tooth implant restoration of the mandibular posterior teeth,the implant depth can substantially affect the accuracy of digital impression,which decreases as the implant depth increases.For a deep implant,the use of a longer scanning rod can improve the scanning accuracy.

To improve the standard of quality control of tazobactam and its preparations in China, national reference standard of tazobactam impurity A was developed. After tazobactam impurity A was synthesized, its structure was validated by infrared (IR), mass spectrometry (MS) and nuclear magnetic resonance (NMR), and its content uniformity and short-term stability were measured and investigated. Then, water content and residue on ignition of impurity A were determined, and its purity was determined using high performance liquid chromatography (HPLC) with 10 mmol/L ammonium acetate solution-acetonitrile (98∶2) as the mobile phase. Mass balance method was used to determine the content of the first batch of tazobactam impurity A national standard substance. Meanwhile, nuclear magnetic quantitative method was used to calculate the content, which was mutually verified with the mass balance method. The developed reference material of tazobactam impurity A is consistent with the maximum degradation impurity in tazobactam system applicability solution and the reference material of tazobactam related substance A contained in USP41. Within the 95% confidence range, the ratio of inter- and intra-bottle variance of impurity A after separation was 0.61 (< F0.05(11,12)), proving that the uniformity was satisfying. The contents of organic impurity, water content and inorganic impurity in impurity A were 0.90%, 1.24% and 0.25%, respectively. The content of impurity A was determined to be 97.6% by mass balance method, which was basically consistent with the result of nuclear magnetic quantitative method (97.1%). Under the condition of 25 °C, the area normalized purity of impurity A was 99.1% at 0, 3, 5 and 10 days, proving that the sample was stable at room temperature for 10 days. Finally the first batch of national standard substance of tazobactam impurity A was established successfully.