In this paper， the name， origin， medicinal parts， producing area， harvesting， processing methods and efficacy of Equiseti Hiemalis Herba（EHH） in famous classical formulas were examined by reviewing related ancient and modern literature. Through textual research， Muzei was first appeared in Zhenyuan Guanglifang（《贞元广利方》）， and used as a mainstream name by later generations. It is also known by other names， such as Cuocao and Bigancao. The main origin of ancient EHH was Equisetum hyemale， which was mixed with E. ramosissimum during the Qing dynasty. The medicinal part was the above-ground part of EHH. In ancient times， the genuine producing area was considered to be Qinzhou， which is now Tianshui city， Gansu. In modern times， EHH produced in Liaoning province is believed to be of higher quality. Currently， the main producing area of EHH circulating in the market is the northeast region in China. EHH with stems that are thick and long， a green color， a thick texture， and clearly visible edges and roughness， but without any easily separating joints being considered the best. The processing methods of the past dynasties mainly included filing， removing knots， stir-baked the crude drugs into black on outside and brown in inside， urine soaking， sun drying and shade drying. In modern times， the main processing method is to first moisturize the plant material， and then cut it into sections before drying. In terms of medicinal properties， EHH is considered by both ancient and modern medicine to have a neutral nature， a slightly sweet and bitter taste， and is non-toxic. Its primary therapeutic effects are related to treating eye diseases， intestinal wind bleeding and uterine bleeding. Based on the research， it is suggested that the dried above-ground part of E. hiemale be used in the development and utilization of famous classical formulas. For the processing requirements are not indicated， it is suggested using raw decoction pieces as medicine， and the processing method refers to the 2020 edition of Chinese Pharmacopoeia. If it is clearly stated that fried charcoal is required， it is recommended to refer to general requirements 0213 of the 2020 edition of Chinese Pharmacopoeia， if it is clearly stated that removing knots is required， it is recommended to follow the ancient method.

This article systematically analyzes the historical evolution of the name， origin， producing area， quality evaluation， harvesting and processing， clinical efficacy of Pyrrosiae Folium by consulting the ancient materia medica， medical books and prescription books， combined with modern literature， in order to provide a reference for the development of famous classical formulas containing this herb. After herbal textual research， it was found that the names of Pyrrosiae Folium in the past dynasties were mostly derived from its color， shape and efficacy. And there were other nicknames such as Shizhe， Shipi and Shilan. Song， Yuan dynasties and before the period， the main origin of Pyrrosiae Folium was Pyrrosia petiolosa， in the Ming dynasty， the main origins were P. petiolosa and P. sheareri， during the Qing dynasty to the present， the main origins were P. sheareri， P. petiolosa and P. lingua. Anciently， the respected Dao-di production area of Pyrrosiae Folium was the area of Lianyungang city， Jiangsu province. In modern times， Anhui and Zhejiang provinces are the main producing areas of P. sheareri， Fujian and Taiwan provinces are the main producing areas of P. lingua， and Guizhou and Hubei provinces are the main producing areas of P. petiolosa. In ancient and modern times， Pyrrosiae Folium with large leaves and thick texture is considered to be the best， the medicinal part is the leaves， and the harvesting and processing methods recorded in the past dynasties were mainly shade-drying after harvesting in the February and July of the lunar calendar， while the modern ones are mostly harvested throughout the year. The processing methods of the past dynasties mainly included removing fuzz by scraping， lightly roasted， frying， fat-fried. However， in modern times， it is mostly used the raw products as a medicine after cleaning， cutting and drying. In ancient times， Pyrrosiae Folium was thought to have a neutral nature with slightly sweet and bitter taste， while in modern times， it is thought to have a slightly cold nature with slightly sweet and bitter taste， and the main effects in ancient and modern times are diuretic， clearing lung-heat， hemostasis and so on. Based on the research results， it is suggested that P. sheareri， P. petiolosa and P. lingua can be used as the medicinal base， processing method can be according to the requirements of formulas， and if the processing requirements are not indicated， the raw products can be selected as the medicine.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

ObjectiveTo analyze the sequence variation and genetic diversity of 47 Isatis indigotica germplasm materials， and carry out the study on the genetic differentiation and structure. MethodGenomic DNA of 47 I. indigotica germplasm materials were extracted by kit extraction method. Two chloroplast DNA （cp DNA） sequences and five inter-simple sequence repeat （ISSR） primers were used for amplification and sequencing. Chromas， Mega 7.0， DanSP5， and GenALEx were used to calibrate， splice， and analyze the sequence characteristics. PERMUT and PopGen 1.31 were used to analyze the genetic diversity parameters and genetic structure， and NTSYS was used to obtain the unweighted pair-group method with arithmetic means（UPGMA） clustering tree plot of 47 I. indigotica germplasm materials. ResultA total of 129 samples from 47 I. indigotica germplasm materials were successfully amplified and sequenced. The length of 2 cp DNA sequences after spliced was 1 412 bp， and there were 377 polymorphic variation loci， and 36 haplotypes. Fu and Li's D* test was significant （P<0.01）. The values of Pi， H_S， and H_T based on cp DNA were 0.119 89， 0.787， and 0.891， respectively. The genetic differentiation coefficients of gene differentiation coefficient（Gst）， nucleotide differentiation coefficient（Nst）， and fixation index（Fst） were 0.117， 0.468， and 0.488， respectively， and the gene flow （Nm） was 0.615. The mean values of PPB， Shannon information diversity index（I）， Nei's genetic diversity index（H）， and Gst based on ISSR were 78.85%， 0.334 8， 0.218 6， and 0.754 4， respectively， and the Nm value was 0.162 8. ConclusionI. indigotica has high genetic diversity and abundant haplotypes at the species level， with abundant haplotypes. Genetic differentiation among different germplasm materials is obvious， and gene exchange is not frequent. Genetic variation mainly exists among populations. The population has accumulated various low-frequency gene mutations recently， suggesting that it has experienced significant regional expansion in the history.

ObjectiveTo conduct genetic variation analysis of 11 cultivars and 7 wild populations of Angelica sinensis in Gansu province based on the chloroplast gene （cp DNA）， and provide references for germplasm identification and breeding of new cultivars of A. sinensis. MethodThree pairs of cp DNA primers were used for polymerase chain reaction （PCR） amplification and sequencing of A. sinensis samples. MegaX was used to perform statistics on sequence characteristics and calculate mean genetic distances among A. sinensis populations. Unweighted pair-group method with arithmetic means （UPGMA） clustering tree based on genetic distance was constructed by NTSYS 2.10e. DanSP v6 was used to calculate sequence polymorphism and Tajima's D of A. sinensis. PERMUT was used to calculate the population structure of A. sinensis. Arlequin v3.5 was used to perform molecular variation analysis， and PopART1.7 was used to construct TCS haplotype network. ResultThree pairs of cp DNA primers were amplified， sequenced， compared， and combined to give a sequence length of 1 759 bp. One variable site was detected in the wild A. sinensis and 480 variable sites were detected in the cultivated A. sinensis， including 97 singleton variable sites， 383 parsimony informative sites， and 152 insertion-deletion sites. In the three regions of matK， psbA-trnH， and rbcL of cp DNA in the wild and cultivated A. sinensis， matK was the region with the highest polymorphism. Tajima’s D of all the combined sequences of A. sinensis were not significantly negative， but psbA-trnH and rbcL genes of the cultivated A. sinensis were significantly negative， indicating that the A. sinensis followed neutral evolution on a whole， while psbA-trnH and rbcL genes had undergone selection. The degree of genetic differentiation （Fst=0） among wild populations was lower than that among cultivated populations （Fst=0.114 19， P<0.05）. The degree of genetic differentiation between wild and cultivated A. sinensis was relatively high （Fst=0.942 55， P<0.01）. Genetic variation in the cultivated A. sinensis was mainly found within the populations （89%）. UPGMA cluster tree based on genetic distance showed that the wild A. sinensis and the cultivated A. sinensis were clustered into one branch， respectively， with a distant genetic relationship， and the population 3 in the cultivated A. sinensis was far from other cultivated populations. The TCS haplotype network consisted of 15 haplotypes and 4 unknown haplotypes， which was divided into 3 parts， with a large number of variations among each part. Shared haplotypes were only found in the wild or cultivated groups， and there were no shared haplotypes between groups. ConclusionThe genetic diversity of A. sinensis was low at species level， and the population diversity of the wild was lower than that of the cultivated. The degree of genetic differentiation between the wild and the cultivated A. sinensis was high， but that in the wild and the cultivated populations were low. Genetic variation in the cultivated A. sinensis was mainly found within populations.

As a digestive organ, the liver has the functions of metabolism, synthesis, and detoxification. It is also an immune organ and plays an important role in maintaining anti-infection, autoimmune stability, and anti-tumor. In particular, the liver has unique immunological advantages. Its immune cells can maintain the liver's immune homeostasis and participate in immunoregulation. A variety of immunotherapy is used in clinical trials for the treatment of difficult and critical liver diseases. This review mainly summarizes the recent clinical trials of immunotherapy in chronic hepatitis B, cirrhosis, hepatocellular carcinoma, and autoimmune liver disease.

Objective:To explore the characteristics of long-lived memory CD8 + T cells and its relationship with disease progression in HIV-1 infected patients. Methods:Twenty-six treatment-na?ve and 26 antiretroviral therapy (ART)-treated HIV-1 infected patients, as well as 11 healthy controls were recruited in this study. Peripheral blood mononuclear cells were isolated and analyzed by flow cytometry to detect the frequency and function of long-lived memory CD8 + T cells. Results:The frequency of long-lived memory CD8 + T cells decreased significantly in treatment-na?ve patients compared with that in healthy controls, and was not fully restored in ART-treated group. In addition, the frequency of long-lived memory CD8 + T cells is positively correlated with CD4 + T cell count and CD4/CD8 ratio, while negatively correlated with HIV-1 viral load. Conclusions:The disease progression in chronic HIV-1 infected individuals is accompanied by continuous damage to long-lived memory CD8 + T cell.

Objective To explore the synergism efficacy and mechanism of Warm Purgative and Strengthening Spleen (WPSS) therapy combined with antibiotics in the treatment of sepsis. Methods Thirty-two SPF Spargue-Dawley (SD) rats were used to replicate the rat sepsis model by cecum ligation perforation (CLP) method and equally divided into model control (MC) group, ceftriaxone group, Chinese herbal medicine (CHM) group and ceftriaxone +CHM group. Eight SD rats underwent sham surgery were used as a sham operation (Sham) group. Rats in Sham and MC groups were administered with 0.9% normal saline (NS) by intraperitoneal injection and gavage. Rats in CHM group were administered with modified Dahuang Fuzi Decoction (DFD, 8 mg/kg) by gavage + 0.9% NS by intraperitoneal injection, Bid. Rats in ceftriaxone group were administered with 0.9% NS by gavage and ceftriaxone (120 mg/kg) by intraperitoneal injection, Bid. Rats in ceftriaxone + CHM group were administered with modified DFD (8 mg/kg) by gavage and ceftriaxone (120 mg/kg) intraperitoneal injection, Bid. The drugs were given for 2 days. The mortality of rats in each group was observed after treatment. The intestinal flora changes and intestinal permeability [intestinal mucosa injury index (IMII), intestinal mucosa secretory immunoglobulin (sIgA), serum D-lactic acid, diamine oxidase (DAO) and sIgA] were detected. Meanwhile, the levels of serum inflammation indexes [lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] were detected. Results ① Mortality: ceftriaxone+CHM group (25.0%) < CHM group (37.5%) and ceftriaxone group (37.5%) < MC group (50.0%), the differences between groups were statistically significant (all P < 0.05). ② 16S rDNA sequencing analysis: the ratio of Bacteroidetesin in MC group was lower than that in the Sham group [(24.36±7.15)% vs. (45.20±6.05)%], and the ratio of Proteobacteria in MC group was higher than that in Sham group [(10.03±7.55)% vs. (0.41±0.21)%]. The diversity of intestinal flora in ceftriaxone group was significantly lower than that in Sham and CHM groups (404.60±17.09 vs. 470.80±16.97, 469.20±14.59), the differences between groups were statistically significant (all P < 0.05). The principal component analysis (PCA) suggested that the composition of CHM group was closer to that of Sham group, which indicated that WPSS therapy could reduce intestinal flora disorders in rats with sepsis. ③The pathological changes of intestinal mucosa: light microscope showed the intestinal mucosa of Sham group was intact; the intestinal mucosa became thinner, and local inflammatory cells had infiltration in MC group. The thickness of intestinal mucosa in CHM, ceftriaxone and CHM+ceftriaxone groups was slightly thicker, and the infiltration of local inflammatory cells was less than that in MC group. The thickness of intestinal mucosa in CHM group and ceftriaxone+CHM group was slightly thicker than that in the ceftriaxone group, and the arrangement was more regular than that in MC group and ceftriaxone group.④Intestinal mucosa permeability and inflammatory state: IMII, D-lactic acid, DAO, LPS, TNF-α and IL-6 of rats in MC group were higher than those of rats in Sham group [IMII: 4.37±0.56 vs. 0.26±0.29, D-lactic acid (mg/L):12.35±0.83 vs. 7.30±1.29, DAO (kU/L): 2.16±0.43 vs. 0.32±0.06, LPS (kU/L): 0.663±0.012 vs. 0.095±0.003, TNF-α (μg/L): 251.03±82.69 vs. 52.15±6.25, IL-6 (μg/L): 160.50±4.77 vs. 54.30±3.36], while sIgA in MC group was lower than that in Sham group (mg/L: 11.57±0.17 vs. 26.76±1.99). IMII, D-lactic acid, DAO, LPS, TNF-α and IL-6 of rats in CHM, ceftriaxone and CHM+ ceftriaxone groups were significantly lower than those of rats in MC group, while sIgA in CHM, ceftriaxone and CHM+ceftriaxone groups were significantly higher than that of rats in MC group. The change of CHM+ceftriaxone group was more significant than those of CHM group and ceftriaxone group [IMII:1.78±0.23 vs. 1.96±0.62, 3.39±0.43, D-lactic acid (mg/L): 8.56±0.37 vs. 9.62±0.57,11.42±0.39, DAO (kU/L):1.14±0.12 vs. 1.72±0.24, 2.01±0.32, sIgA (mg/L): 25.34±1.49 vs. 23.99±7.85, 17.46±1.20, LPS (kU/L):0.302±0.007 vs. 0.387±0.004, 0.715±0.013, TNF-α (μg/L): 57.10±3.98 vs. 101.49±21.49, 141.91±20.20, IL-6 (μg/L): 93.71±2.39 vs. 87.12±7.31, 104.27±1.84]. Conclusion WPSS therapy may improve the efficacy of antibiotics in the treatment of sepsis by regulating the intestinal flora and reducing the intestinal mucosa permeability and inflammation level.

Objective To assess and compare the incidence,clinical characteristics,treatment,and prognosis of acute heart failure patients from different grades hospitals in Beijing.Methods In this prospective internet prognosis registered study (Beijing AHF Registry),a total of 3 335 consecutive patients admitted to 14 emergency departments in Beijing from January 1st 2011 to September 23rd 2012 were enrolled.According to hospital grade,these patients were divided into two groups,349 patients were from secondary hospitals,and 2 956 patients were from tertiary hospitals.Results Among the 3 335 patients,the medium age was 71 (58,79) years,and male accounted for 53.16％.The most common underlying disease were coronary disease (43.27％),hypertension (17.73％),cardiomyopathy (16.07％) etc.The average treatment time in Emergency Department was 66.82 h.The emergency department mortality rate was 3.81％ (127 cases).The 30-day and 1-year cumulative all-cause mortality were 15.3％ and 32.27％,respectively.The 30-day and 1-year cumulative all-cause readmission were 15.64％ and 46.89％,respectively.Compared with patients in tertiary hospitals,patients in secondary hospitals had more onset acute heart failure patients (63.64％ vs.49.93％),shorter emergency department treatment time (12 h vs.41 h),lower discharge rate (3.43％ vs.37.45％) and emergency department mortality(1.58％ vs.4.09％).Compared with those in tertiary hospitals,1-year cumulative all-cause mortality (25.6％ vs.33.2％),cardiovascular disease mortality (20.2％ vs.26.0％),aggravated heart failure mortality (22.4％ vs.28.8％) were lower in secondary hospitals.Following propensity score matching,compared to tertiary hospitals,patients in secondary hospitals showed lower utilization rate of beta-blockers and ACEFARB (4.51％ vs.28.17％,1.41％ vs.9.58％),except the pironolactone.Conclusion Acute heart failure in emergency department is associated with a high mortality rate and readmission rate.There is still a big gap between guidelines recommend medication current treatments for acute heart failure.