Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial.

BACKGROUND: Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596). RESULTS: A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28], with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802). CONCLUSIONS: NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.

[Longdan Xiegan Decoction and its interpretation from the perspective of meridians].

By systematically examing through Longdan Xiegan Decoction in medical books of the past dynasties, it was found that the Longdan Xiegan Decoction recorded in Lan Shi Mi Cang mainly targeted men's genital odor at frist. After Xue Ji's addition and subtraction, the scope of the prescription was gradually generalized and expanded, and confusion its name, composition and source of the prescription appeared, which was particularly prominent in Jingyue Quanshu and Yifang Jijie.Doctors used to interpret this prescription from the perspective of viscera. In order to better understand the main treatment rules of Longdan Xiegan Decoction, it is necessary to change the perspective and reinterpreted it from the perspective of meridians.Attributing the symptoms of the perineum to Liver Meridian of Foot-Jueyin,hypochondriac pain, deafness and other symptoms to the Gallbladder Meridian of Foot-Shaoyang, and adding or subtracting herbs according to the specific conditions, is not only conducive to a comprehensive and in-depth understanding of the prescription to achieve accurate clinical syndrome differentiation and medication, but also prompts modern researchers to rethink the important role of meridian theory in the formation and development of the theoretical system of traditional Chinese medicine.

[Causality in objective world: Directed Acyclic Graphs-based structural parsing].

The overall details of causality frames in the objective world remain obscure, which poses difficulty for causality research. Based on the temporality of cause and effect, the objective world is divided into three time zones and two time points, in which the causal relationships of the variables are parsed by using Directed Acyclic Graphs (DAGs). Causal DAGs of the world (or causal web) is composed of two parts. One is basic or core to the whole DAGs, formed by the combination of any one variable originating from each time unit mentioned above. Cause effect is affected by the confounding only. The other is an internal DAGs within each time unit representing a parent-child or ancestor-descendant relationship, which exhibits a structure similar to the confounding. This paper summarizes the construction of causality frames for objective world research (causal DAGs), and clarify a structural basis for the control of the confounding in effect estimate.

[A structural classification of strategies for confounding control in research design].

Confounding affects the causal relation among the population. Depending on whether the confounders are known, measurable or measured, they can be divided into four categories. Based on Directed Acyclic Graphs, the strategies for confounding control can be classified as (1) the broken-confounding-path method, which can be further divided into single and dual broken paths, corresponding to exposure complete intervention, restriction and stratification, (2) and the reserved-confounding-path method, which can be further divided into incomplete exposure intervention (in instrumental variable design and non-perfect random control test), mediator method and matching method. Among them, random control test, instrumental variable design or Mendelian randomized design, mediator method can meet the requirements for controlling all four types of confounders, while the restriction, stratification and matching methods are only applicable to known, measurable and measured confounders. Identifying the mechanisms of confounding control is a prerequisite for obtaining correct causal effect estimates, which will be helpful in research design.

[Exposure-preceding-outcome regarding time sequence among cohort studies in real world].

One of the commonly accepted merits of cohort studies (CSs) refers to the exposure precedes outcome superior to other observational designs. We use Directed Acyclic Graphs to construct a causal graph among research populations under CSs. We notice that the substitution of research population in place of a susceptible one can be used for effect estimation. Its correctness depends on the outcome-free status of the substituted population and the performance of both screening and diagnosis regarding the outcomes under study at baseline. The temporal precedence of exposure over outcome occurs theoretically, despite the opposite happens in realities. Correct effect estimate is affected by both the suitability of population substitution and the validities of outcome identification and exclusion.

High prevalence of albuminuria in population-based patients diagnosed with type 2 diabetes in the Shanghai downtown.

OBJECTIVE: The prevalence of albuminuria and the risk factors associated with albuminuria were evaluated among the Chinese patients diagnosed with type 2 diabetes aged over 30 in the Shanghai downtown. We also evaluated the variability of urinary albumin-to-creatinine ratio (ACR) among the three measurements and the relationship between diabetic retinopathy (DR) and albuminuria. METHODS: The 1039 Chinese patients diagnosed with type 2 diabetes aged over 30 were investigated by randomized cluster sampling in the Shanghai downtown and 1018 patients were analyzed in this study. Body mass measurements including height, weight, waist circumference and hip circumference, resting blood pressure, fasting blood measures, urinary ACR and the digitally stored fundus images were investigated. The prevalence of albuminuria was calculated and the risk factors associated with albuminuria were evaluated by stepwise logistic regression. The concordance of urinary ACR was evaluated by observed agreement. The relationship between albuminuria and DR was also evaluated. RESULTS: (1) The mean age of all patients was 66.10+/-11.54 years and the duration of diabetes was 7.89+/-7.16 years. (2) The prevalence of albuminuria was 49.6% among the Chinese patients diagnosed with type 2 diabetes aged over 30 in the Shanghai downtown, 41.4% with microalbuminuria and 8.2% with macroalbuminuria. (3) Microalbuminuria was significantly associated with systolic blood pressure, gender and waist circumference. Macroalbuminuria was significantly associated with systolic blood pressure and duration of diabetes. (4) Observed agreement among the three urinary ACR measurement for albuminuria staging was 73.3% (first versus second), 64.5% (first versus third) and 77.5% (second versus third). Observed agreement in the albuminuria staging between the single urinary ACR measurement and all three urinary ACR measurements was 85.8% (first versus all three), 87.6% (second versus all three) and 81.9% (third versus all three). (5) The percentage of DR in the macroalbuminuric group (59.2%) was significantly higher than that in the normalbuminuria group (16.1%) and microalbuminuria group (24.6%). (6) The macroalbuminuric patients with DR had significantly increased fasting blood glucose and HbA1c compared with the macroalbuminuric patients without DR. CONCLUSION: The prevalence of microalbuminuria observed in the Chinese patients diagnosed with type 2 diabetes aged over 30 in the Shanghai downtown reached up to 41.4% though the observations in our study might be representative of the diabetic patients of the Shanghai downtown. We agreed that at least two of the three urinary collections were done in a 3- to 6-month period because of the day-to-day variability in albumin excretion. The percentage of DR among the patients with macroalbuminuria was 59.2%, and the macroalbuminuric patients with the significantly high plasma glucose and DR were prone to diagnose DN.

[Directed acyclic graphs: languages, rules and applications].

Nearly all scientific studies explore causality, which will be met by directed acyclic graphs (DAGs). This paper systematically introduces graphic language, basic and interference rules of DAGs, and their applications into identifying research questions, understanding and undertaking research designs, guiding data analysis, classifying biases, etc. DAGs play key roles in causality studies.

Acupuncture point injection treatment of primary dysmenorrhoea: a randomised, double blind, controlled study.

OBJECTIVE: To determine if injection of vitamin K3 in an acupuncture point is optimal for the treatment of primary dysmenorrhoea, when compared with 2 other injection treatments. SETTING: A Menstrual Disorder Centre at a public hospital in Shanghai, China. PARTICIPANTS: Chinese women aged 14-25 years with severe primary dysmenorrhoea for at least 6 months not relieved by any other treatment were recruited. Exclusion criteria were the use of oral contraceptives, intrauterine devices or anticoagulant drugs, pregnancy, history of abdominal surgery, participation in other therapies for pain and diagnosis of secondary dysmenorrhoea. Eighty patients with primary dysmenorrhoea, as defined on a 4-grade scale, completed the study. Two patients withdrew after randomisation. INTERVENTIONS: A double-blind, double-dummy, randomised controlled trial compared vitamin K3 acupuncture point injection to saline acupuncture point injection and vitamin K3 deep muscle injection. Patients in each group received 3 injections at a single treatment visit. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the difference in subjective perception of pain as measured by an 11 unit Numeric Rating Scale (NRS). Secondary measurements were Cox Pain Intensity and Duration scales and the consumption of analgesic tablets before and after treatment and during 6 following cycles. RESULTS: Patients in all 3 groups experienced pain relief from the injection treatments. Differences in NRS measured mean pain scores between the 2 active control groups were less than 1 unit (-0.71, CI -1.37 to -0.05) and not significant, but the differences in average scores between the treatment hypothesised to be optimal and both active control groups (1.11, CI 0.45 to 1.78) and (1.82, CI 1.45 to 2.49) were statistically significant in adjusted mixed-effects models. Menstrual distress and use of analgesics were diminished for 6 months post-treatment. CONCLUSIONS: Acupuncture point injection of vitamin K3 relieves menstrual pain rapidly and is a useful treatment in an urban outpatient clinic. TRIAL REGISTRATION NUMBER: NCT00104546; Results.

I148M variant of PNPLA3 increases the susceptibility to non-alcoholic fatty liver disease caused by obesity and metabolic disorders.

BACKGROUND: The patatin-like phospholipase 3 (PNPLA3) rs738409 gene polymorphism is an important genetic determinant of non-alcoholic fatty liver disease (NAFLD). However, the associations between liver fat and metabolic traits in rs738409 G allele carriers and the allelic influence on this association have not been fully studied. AIM: To investigate the influence of the PNPLA3 gene polymorphism on the association of liver fat with serum metabolic factors and carotid atherosclerosis. METHODS: Liver fat was measured by quantitative ultrasound in 4300 subjects in the Shanghai Changfeng community and analysed for its association with obesity and metabolic factors in individuals with the PNPLA3 CC, CG and GG genotypes. RESULTS: Non-alcoholic fatty liver disease occurred in 37.9% and 28.8% of the subjects with the GG and CC genotypes respectively (P < 0.001). Liver fat was significantly associated with body mass index, waist circumference, serum triglycerides, high-density lipoprotein cholesterol, fasting blood glucose and insulin in the PNPLA3 rs738409 G allele carriers (P < 0.001). Compared with the CC homozygotes, the GG homozygotes presented higher liver fat and liver fibrosis scores despite their better metabolic status (comparison of regression line slopes, P < 0.05). An increase in liver fat was accompanied by a significant increase in the average and maximum carotid intima-media thickness in subjects with the PNPLA3 CC genotype but not in those with the GG genotype. CONCLUSIONS: PNPLA3 rs738409 G allele carriers were found to be more susceptible to the metabolic-related hepatic steatosis, and developed NAFLD and liver fibrosis despite presenting relatively better metabolic statuses and lower risks for carotid atherosclerosis.

[Studies on the origin of different discharge pattern of the two types of phrenic motoneurones by cross-correlation analysis].

Experiments were performed on twenty five anesthetized, paralyzed, vagotomized and artificially ventilated rabbits. Discharges of single phrenic nerve fibers were recorded. According to their discharge patterns, phrenic motoneurones were divided into two types: tonic units (TU) and phasic units (PU). A cross-correlation analysis was done between TU and TU, PU and PU, or TU and PU. In 21/36 pairs of phrenic motoneurones, the cross-correlation histogram showed a significant central peak, which represented synchronization of the pair of units resulting from a common input. There were three types of synchronization: short-term, broad peak and high frequency-oscillatory synchronization. The difference in synchronization number between heterogeneous pairs (1 TU and 1PU, 2/10 showing synchronization) and homogeneous pairs (2 TU or 2 PU, 19/26 showing synchronization) was statistically significant (x2-test, P less than 0.05). These results suggest that TU and PU have different central inputs, which result in their different discharge patterns between the TU and PU.