Currently， there are many difficulties in formulating recommendations of traditional Chinese medicine （TCM） clinical practice guidelines. This paper analyzed and summarized the unique or prominent difficult issues in the formulation of recommendations faced by TCM guidelines， such as experts' professional background and experience bringing about the preferance from the academic emotion， inconsistency between different academic schools making it difficult to reach consensus， lack of guiding principles of the decision weight of different dimensions for recommendations. Therefore， methodological suggestions have been put forward， including organizing parallel TCM and western medicine consensus group， improving the method of combining TCM and western medicine paradigm， attaching great importance to the evidence-based governance of academic schools， and promoting the research on different dimensions for recommendation formulation， which may provide a methodological reference for the guideline development.

Syndrome differentiation and treatment is a unique mode of diagnosis in traditional Chinese medicine （TCM）. The establishment of scientific and standardized syndrome diagnosis standards is an important link to evaluate the clinical efficacy of TCM objectively and systematically， and also a prerequisite for the promotion and development of TCM to obtain international recognition. This article reviewed the basic modes and existed problems of the current syndrome diagnosis criteria， and proposed to construct a multidimensional core information set integrating the minimized core symptoms， the artificial intelligence signs， the multi-modal laboratory indicators， and multi-omics specific markers， so as to present syndrome characteristics from multiple perspectives systematically. This paper also described the basic mode， constructure， as well as the process and methodology to be adopted in the establishment of the standardized diagnostic research method. The core information set of diagnostic symptoms not only took into account the specificity of the disease， but also improved the inconsistency due to the complexity and subjectivity of the syndrome differentiation， thereby providing a methodological basis for the standardization of TCM syndrome differentiation in clinical research.

Abstract: Objective To analyze the causes of foodborne illness outbreaks in Inner Mongolia, so as to provide reference for understanding systemic risks and formulating prevention and control measures. Methods Data on foodborne disease outbreaks in Inner Mongolia Autonomous Region from 2016 to 2021 were collected through the "Foodborne Disease Outbreak Monitoring System" for attribution analysis. Results A total of 591 outbreak events were included from 2016 to 2021. Single -dimensional attribution analysis showed that the main causes of foodborne disease outbreaks in this region were vegetables and vegetable products, and meat and meat products, respectively accounting for 20.5% (121/591) and 12.6% (75/591) of the total events. leading contributing factor was improper processing, accounting for 16.2%(96/591), and the main pathogenic factor was toxic plants and their toxins, accounting for 14.9%(88/591). Multi-dimensional attribution analysis showed that the highest number of outbreak events occurred in summer, with 290 cases accounting for 49.1% (290/591) of the total number of events. The eastern, central, and western regions also had the highest number of events in summer, accounting for 53.6% (180/336), 39.5% (60/152), and 48.5% (50/103) of the total number of events in this region, respectively. Among vegetables and vegetable products, improper processing led to the majority of outbreaks caused by toxic plants and their toxins, accounting for 58.7% (71/121) of total events. For meat and meat products, improper storage resulting in the most outbreaks of biological pollution, accounting for 16.0%(12/75) of the total number of meat and meat product incidents. Majorities of death cases were primarily due to accidental ingestion or misuse of non-food items (such as poisonous mushrooms), comprising 38.5% (5/13) of total deaths. Conclusions The main food, triggering factors, and pathogenic factors involved in the outbreak of foodborne diseases in this region are relatively routine and controllable. Therefore, efforts should be made to strengthen public food safety education to reduce the occurrence of foodborne diseases.

Objective:To summarize the clinical features and prognosis of acute kidney injury in patients with HBV related acute on chronic liver failure (ACLF).Methods:A total of 150 patients who developed acute kidney injury (AKI) in patients with HBV related ACLF from Sep. 2010 to Sep. 2019 were reviewed retrospectively, and the gender, age, laboratory examination, Child-pugh scores, and model for end-stage liver disease (MELD) were collected and the survival of the patients were followed up to analyze the prognosis.Results:Ninety-three percent of the patients were complicated with ascites, 81% with spontaneous peritonitis, 65% with hepatic encephalopathy and 58.7% with pulmonary infection; 60 patients (60.0%) were AKI stage 1, 44 patients (29.3%) were AKI stage 2, 16 patients (10.7%) were AKI stage 3. The patients with hyponatremia had lower albumin ( t=2.571, P=0.011), higher blood urea nitrogen, serum potassium and white blood cell levels than those without hyponatremia ( t=3.184, P=0.002; t=2.069, P=0.040; t=2.251, P=0.026); 74.7% of the patients died within 30 days, and the 90 days survival rate was 16.7%. The 30 days and 90 days mortality of patients with hyponatremia was higher than that of patients without hyponatremia ( χ2=4.11, P=0.044; χ2=3.901, P=0.049 7). Kaplan-Meier analysis revealed that the patients who had abnormal uric acid pre-diagnosis of AKI, hyponatremia when diagnosis of AKI, organ damage other than liver and kidney, metabolic acidosis, upper gastrointestinal tract bleeding, hepatic encephalopathy had a poor survival. Cox regression analysis showed that other organ function damage other than liver and kidney, metabolic acidosis, and the old age, were independent risk factors of death. Conclusions:Most of the AKI patients with HBV related ACLF had ascites and spontaneous bacterial peritonitis when AKI occurred, and AKI stage 1 was common. The mortality of patients with hyponatremia was high, and the risk of death was high in patients with severe organ damage other than liver and kidney, metabolic acidosis and the old age.

Objective Antiviral therapy should be adopted for chronic hepatitis B (CHB) patients with significant liver fibrosis to decrease the risk of liver related complications.Fibrosis assessment during antiviral treatment is a key step in antiviral therapy evaluation.Liver biopsy is the gold standard for assessing the degree of liver fibrosis.However,liver biopsy is difficult to perform more than one time after a long-term effective treatment because of the cost and risk of life-threatening complications.In this study we aimed to evaluate changes of liver fibrosis during 4 years of entecavir(ETV) treatment by non-invasive fibrosis markers in CHB patients who need antiviral therapy.Methods Totally 268 HBeAg negative treatment-naive CHB patients were enrolled and liver biopsy were performed before starting antiviral therapy in this study.Totally173 patients who needed antiviral therapy (liver fibrosis stages≥ F2,Metavir scoring system) were treated with ETV for at least 4 year.A clinical and virological evaluation was performed at baseline and again at 12,24,36 and 48 months during ETV treatment.Fibrosis-4 (FIB-4) index was used to assess dynamic changes of liver fibrosis in HBeAg negative CHB patients after 1,2,3 and 4 years of ETV treatment.Results Liver biopsy was performed for all enrolled patients at baseline.According to Metavir fibrosis stages,numbers of patients with FI,F2,F3 and F4 were 95,108,50 and 15,respectively.The FIB-4 index enabled the effective identification of patients with severe fibrosis (Metavir F3-F4) with an area under the ROC curve of 0.775 (95％CI 0.716-0.834).The FIB-4 values significantly decreased in F2 and F3 patients after 1 and 2 years ETV therapy (P＜0.01),respectively.But for F4 patients,FIB-4 values decreased significantly at year 4 (P＜0.05).Conclusions FIB-4 values decreased significantly during 4-year ETV treatment in HBeAg-negative CHB patients indicating that these noninvasive fibrosis tests might be useful for monitoring improvement of liver fibrosis and assessing treatment efficacy during long-term ETV treatment.

Objective:To investigate the association between the pathogenesis of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B and the frequency and function of plasmacytoid dendritic cell (pDC) in patients HBeAg-positive chronic hepatitis B virus infection.Methods:A total of 49 HBeAg (+ ) patients with chronic hepatitis B virus infection in immune tolerance phase (IT) and 100 patients in immune clearance phase (IC) were enrolled. The viral serological indicators and liver function were detected. Peripheral venous blood samples were collected. The peripheral blood pDC frequency and the quantitative expression of co-stimulatory molecule CD86 were detected by flow cytometry, and the correlation between the onset of chronic hepatitis B and the frequency and function of pDC was analyzed.Results:In IC group, hepatitis B surface antigen (HBsAg) levels, HBeAg levels and hepatitis B virus (HBV) DNA loads were significantly lower than those in IT group, and alanine aminotransferase (ALT) levels in IC group were significantly higher than that in IT group; pDC% in IC group was significantly lower than that in IT group; CD86 + pDC% and CD86 mean fluorescentintensity (MFI) showed no significant difference between the two groups. In the IC group, the baseline pDC% was negatively correlated with ALT levels, while CD86 + pDC%, CD86MFI, and CD86 antibody binding capacity (ABC) had no remarkable correlation with ALT levels. Conclusions:The frequency of pDC was correlated with the pathogenesis of CHB. The lower the frequency of pDC in patients with CHB, the more prone to hepatitis. Therefore, increasing the frequency of pDC may inhibit the occurrence of hepatitis.

Objective To investigate the clinical and biological features of patients with mixed﹣phenotype acute leukemia (MPAL). Methods The clinical data of 24 de novo adult patients with MPAL who were admitted to Fujian Medical University Union Hospital from January 2012 to October 2018 were retrospectively analyzed. These patients were diagnosed according to the World Health Organization (WHO) 2016 criteria. The clinical and biological characteristics of the patients were analyzed by morphological and cytochemical staining, immunophenotyping, cytogenetics and molecular biology. Results Of the 24 patients, 16 were male and 8 were female, and the median age of the patients at diagnosis was 27 years old (5-66 years old). The average blasts of bone marrow were (57.41 ±23.20)% . Thirteen cases (54.2% ) were diagnosed as MPAL morphologically, while 5 cases (20.8% ) were diagnosed as acute myeloid leukemia (AML), 5 cases (20.8%) were diagnosed as acute lymphoblastic leukemia (ALL) and 1 case (4.2%) was inconclusive. Eighteen patients (75.0%) co﹣expressed B﹣lymphoid and myeloid markers, while 5 patients (20.8%) with T﹣lymphoid and myeloid markers and 1 patient (4.2%) with B﹣lymphoid and T﹣lymphoid markers, respectively. The positive rate [median (range)] of CD38, HLA﹣DR and CD34 was 90.5% (0.1%-99.7%), 90.1% (1.1%-98.8% ) and 81.3% (0.1%-97.8%), respectively. Eighteen cases underwent chromosome examination, of which 5 cases carried with t(9;22)(q34;q11), 3 cases with t(v;11q23.3), 2 cases with complex karyotypes, and 2 cases with t(9;22)(q34;q11) and complex karyotypes, respectively. Twenty﹣one cases underwent genetic examination, of which 6 cases were positive for BCR﹣ABL, 3 cases were positive for MLL, 1 case was positive for MLL and BCR﹣ABL, 1 case was positive for BCR﹣ABL and TP53, and 1 case was positive for PHF6 and ASXL1 respectively. Of the 24 patients, 7 refused chemotherapy and 17 received induction chemotherapy. Of the patients receiving chemotherapy, 9 cases achieved complete remission (CR), 1 case was partial remission (PR), and 7 cases were not relieved (NR). In 11 patients treated by ALL﹣type induction regimen and 6 patients treated by ALL and AML﹣type induction regimen, 8 cases and 1 case achieved CR, the difference in CR rate was statistically significant (P<0.05). In 6 patients with Philadelphia chromosome (Ph) positive and 11 patients with Ph negative, 1 case and 8 cases achieved CR, the difference in CR rate was statistically significant (P<0.05). The median follow﹣up time was 5.5 months (0-36 months). The 3﹣year overall survival (OS) rate was 17.5% and the median OS time was 6 months. The 3﹣year OS rates in the allogeneic hematopoietic stem cell transplantation and non﹣transplanted groups were 75.2% and 0, respectively, and the median OS time was not reached and 4 months (P< 0.05). Conclusions MPAL is rare, it mostly co﹣expresses lymphoid and myeloid antigens and shows a much higher incidence of CD34, CD38 and HLA﹣DR. MPAL is often associated with Ph positive and complex karyotypes. MPAL has a low remission rate and poor prognosis, and a reasonable and effective treatment plan should be further explored.

Objective: To investigate the correlation between the frequency and function of early plasmacytoid dendritic cells (pDC) and the treatment response in patients with HBeAg-positive chronic hepatitis B receiving entecavir (ETV). Methods: Patients with HBeAg-positive chronic hepatitis B were enrolled. Antiviral therapy with ETV, serum serological markerso hepatitis B virs (HBV) infection and liver function (HBV DNA load, HBsAg/anti-HBs, HBeAg and anti-HBe levels, and ALT levels) were monitored every three months before and during treatment; the efficacy of ETV was assessed by changes in the level of HBV DNA. Peripheral venous blood was collected before treatment, at 12 weeks and 24 weeks, respectively. Flow cytometry was used to detect the frequency of peripheral blood pDC and the surface co-stimulatory molecule CD86. The baseline and early treatment (12 weeks and 24 weeks) pDC frequency and functional changes were analyzed. Results: Of the 100 patients with chronic hepatitis B, 45 patients received ETV treatment and 48 weeks of follow-up. Within 48 weeks of ETV treatment, HBsAg levels decreased by 0.53±0.78 log IU/mL; HBeAg decreased by 816.61S/CO, and HBeAg seroconversion occurred in 4 cases; HBV DNA content decreased by 6.04±1.12 log IU/mL, in 33 cases (73%) the HBV DNA became undetectable, in 43 cases ALT kept normal continuously for more than 3 months. In the early stage of ETV treatment, pDC% increased significantly, CD86+ pDC%, CD86MFI and CD86ABC showed no significant changes. In ETV-treated HBV DNA responders, pDC% increased significantly, CD86+ pDC%, CD86MFI and CD86ABC showed no significant changes; HBV DNA non-responders had a significant increase in pDC%, but CD86+ pDC% decreased significantly, and CD86MFI and CD86ABC showed no significant changes. The decrease in HBsAg and HBeAg levels in ETV treated patients was not significantly associated with early pDC%, CD86+ pDC%, CD86MFI and CD86ABC changes. Conclusions ETV treatment can directly inhibit the replication of HBV DNA, but does not enhance the function of immune cells.

Objective: To explore the association between the efficacy of peg-IFN and the complexity of TP and RT regions of hepatitis B virus (HBV) in chronic hepatitis B. Methods: Patients with HBeAg positive, HBV DNA positive chronic hepatitis B were given peg-interferon 180 μg once a week for subcutaneous injection, and baseline information was collected from baseline and after 12 weeks’ treatment. The baseline HBV DNA TP and RT fragments were amplified, database, high-throughput sequencing, and the average genetic distance calculation. Results: Data of 108 patients were analyzed by logistic regression. RT area fragment Markov distance and TP area fragment Shannon quotient for HBV DNA response were calculated. ALT level is good for HBeAg response. HBsAg level is bad for HBsAg response. Conclusions The complexity of the baseline TP and RT regions may be associated with the efficacy of peg-interferon therapy for CHB.

Objective: We aimed to evaluate changes towards liver fibrosis during entecavir(ETV)treatment by non-invasive fibrosis markers in chronic hepatitis B (CHB) patients who need antiviral therapy. Methods: Totally 303 HBeAg negative treatment-naive CHB patients were enrolled and liver biopsy was performed before starting antiviral therapy in this study. Totally 196 patients who need antiviral therapy were treated with ETV for at least 3 years. A clinical and virological evaluation was performed at baseline and again after 1, 2 and 3 years during ETV treatment. AST-to-platelet ratio index (APRI) was used to assess dynamic changes of liver fibrosis in HBeAg negative CHB patients after 1, 2, 3 years of ETV treatment. Results: All enrolled patients experienced liver biopsy at baseline. According to Metavir fibrosis stages, F1, F2, F3 and F4 patients were 107, 125, 54 and 17, respectively. The APRI score enabled the correct identification of patients with severe fibrosis (METAVIR F3-F4). The APRI values significantly decreased in F2 and F3 patients after 1 year ETV therapy (P<0.01). But for F4 patients, APRI values decreased significantly at year 3 (P<0.05). Conclusions APRI values decreased significantly during ETV treatment in HBeAg-negative CHB patients indicating that these noninvasive fibrosis tests might be useful for monitoring improvement of liver fibrosis and assessing treatment efficacy during long-term ETV treatment.