Treatment of Bone and Joint Diseases with Gancao Fuzitang： A Review / 中国实验方剂学杂志

Gancao Fuzitang originates from the Treatise on Febrile Diseases and Miscellaneous Diseases （《伤寒杂病论》） and is mainly used to treat pain in the bones and joints and symptoms such as no flexion or extension. It has the effect of tonifying the spleen and kidney and removing dampness and turbidity， so it is widely used in the clinical treatment of various bone and joint diseases. This article reviewed the clinical research and mechanism of Gancao Fuzitang in the treatment of bone and joint diseases. The research has found that this prescription has good efficacy in treating bone and joint diseases such as rheumatoid arthritis， rheumatoid arthritis， ankylosing spondylitis， gout， and intervertebral disc herniation. Its mechanism of action may be related to regulating the level of inflammatory factors， antioxidation， and the protein expression of inflammatory and apoptotic cell-related pathways， improving bone and joint diseases， and alleviating related symptoms. This study can provide a reference for further deepening the research on the prevention and treatment of bone and joint diseases with Gancao Fuzitang.

Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine（Part 5）： Retrieval and Synthesis of Key Information on Rational Drug Use / 中医杂志

Recommendations for Chinese patent medicine （CPM） based on key information on rational drug use are one of the important conditions for enhancing guideline enforceability as well as facilitating guideline implementation. In this study， we discussed in detail of the key information on the rational use of CPM in five aspects， which are dosage， drug discontinuation， drug-drug and drug-food interactions， safety and economy. Following the process of multi-source search， synthesis and prioritization， it is suggested to collect key information on the rational use of CPM from a multi-source search of drug instructions， policy documents， literature， and clinical experts' experiences. Then the searched information should be summarized and prioritized with the principle that taking drug instructions as the basis and other-sources information for check and supplementation. Finally， methodological recommendations for the retrieval and synthesis of key information on rational drug use in guideline recommendations has been formed.

Methodology for the Development of Clinical Practice Guideline for Chinese Patent Medicine（Part 1）： Development Status and Characteristics / 中医杂志

The irrational use of Chinese patent medicines （CPM） is becoming more and more prominent， which makes the demand for clinical practice guidelines of CPM gradually increase. In order to make domestic scholars understand the latest developments and existing problems of the CPM guidelines， and promote its development， this paper introduced the concept of CPM guidelines， summarized the characteristics of the two development modes， namely “taking CPM as the key” and “taking disease/syndrome as the key”， and analyzed the current methodological status of developing and reporting CPM guidelines. Based on the existed problems， three suggestions have been put forward to optimize the quality of CPM guidelines， which were clarifying the target users and scope of CPM guidelines， establishing an open and transparent mechanism of the personnel involvement and process steps， and formulating implementable and operable recommendations for the use of CPM.

Evaluation of asymptomatic ocular surface disorders in hospitalized patients with primary pterygium before surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the preoperative ocular symptoms and the characteristics of asymptomatic ocular surface abnormalities in hospitalized patients with primary pterygium.METHODS: Cross-sectional study. Hospitalized patients diagnosed with primary pterygium and scheduled to receive pterygium excision surgery at the Xiamen Eye Center of Xiamen University from August 2022 to October 2022 were enrolled. Ocular surface disease index questionnaire(OSDI), six examinations including non-invasive tear film break-up time, Schirmer I test, tear meniscus height, lid margin abnormality, meibomian gland dropout and tear film lipid layer thickness, and anterior segment optical coherence tomography(AS-OCT)were performed and statistically analyzed.RESULTS: A total of 178 cases(178 eyes), with a mean age of 54.39±10.75 years old, were recruited, including 75 males(42.1%)and 103 females(57.9%). The average values of ocular surface parameters in these patients included OSDI: 11.47±9.69, tear film break-up time: 7.10±3.86 s; tear meniscus height: 0.16±0.07 mm, Schirmer I test values: 14.39±7.29 mm/5 min, and pterygium thickness: 504.74±175.87 μm. Totally 161 eyes(90.4%)presented with abnormal lid margin, 44 eyes(24.7%)presented with meibomian gland dropout score ≥4, 52 eyes(29.2%)presented with low lipid layer thickness. In the 6 objective examinations, abnormalities in at least 4 of these tests were found in 85.4% of eyes. Pterygium morphology was classified into four grades: 10 eyes(5.6%)of grade Ⅰ, 93 eyes(52.2%)of grade Ⅱ, 60 eyes(33.7%)of grade Ⅲ, and 15 eyes(8.4%)of grade Ⅳ. In patients with a higher grade of pterygium, the tear film break-up time was lower, and the proportion of abnormal lid margin was also significantly higher(P<0.05). The patients were further divided into two subgroups, including 121 eyes(68.0%)with normal OSDI <13 in the normal group and 57 eyes(32.0%)with OSDI ≥13 in the abnormal group. No significant difference was found in the proportion of meibomian gland dysfunction between the two groups of patients(71.9% vs. 71.9%, P=0.872). In addition, there were differences in the number of abnormal objective examinations(4.11±0.85 vs. 4.91±0.99, P<0.001).CONCLUSIONS: Asymptomatic ocular surface abnormalities were present preoperatively in patients hospitalized for primary pterygium. A comparable high incidence of structural or functional meibomian gland dysfunction existed in pterygium patients with or without apparent ocular discomfort. More attention should be paid to the ocular surface abnormalities in those asymptomatic patients before primary pterygium surgery.

Interpretation of the Guideline for Multi-dimensional and Multi-criteria Comprehensive Evaluation of Chinese Patent Medicine：weighting of evaluation indicators / 中国药房

OBJECTIVE To provide a detailed report and interpretation of the method and results for determining the weights of the technical indicators from the “multi-dimensional and multi-criteria comprehensive evaluation index system （first edition）” stated in Guideline for Multi-dimensional and Multi-criteria Comprehensive Evaluation of Chinese Patent Medicine. METHODS Normalization calculations were performed on the comprehensive weight values calculated by the analytic hierarchy process and expert weighting method to obtain the objective weights of the indicators. RESULTS The weight results of the six primary dimensions in the current comprehensive evaluation indicator system of Chinese patent medicine showed effectiveness dimension＞ safety dimension＞standard dimension＞application dimension＞scientific dimension＞economic dimension， with weight values of 0.281 0， 0.268 5， 0.195 8， 0.107 3， 0.096 1 and 0.051 3 respectively， consistent with the results of most researches currently. CONCLUSIONS The process of weight determination in this indicator system is scientifically reasonable， with clear methods and clear interpretations， and is worthy of further optimization and widespread application.

Sishenwan Combined with Tongxie Yaofang Treats Ulcerative Colitis with Spleen-kidney Yang Deficiency and Liver Depression / 中国实验方剂学杂志

ObjectiveTo induce the rat model of ulcerative colitis （UC） with spleen-kidney Yang deficiency and liver depression， and explore the efficacy and mechanism of Sishenwan combined with Tongxie Yaofang （SSW&TXYF） based on the therapeutic principles of tonifying spleen， soothing liver， warming kidney， and astringing intestine. MethodSixty male SD rats were randomized into normal， model， mesalazine， and high-， medium-， and low-dose SSW&TXYF groups. The rats in other groups except the normal group were administrated with Sennae Folium decoction and hydrocortisone and received tail clamping for 14 days. On day 14， rats received enema with TNBS-ethanol solution to induce UC. The rats were administrated with corresponding drugs from day 15 of modeling， and the body weight and mental state were observed and recorded. The sucrose preference test was performed from day 25. On day 28， the rectal temperature was measured， and the rats were administrated with 3% D-xylose solution at a dose of 10 mL·kg-1 by gavage. Blood was sampled 1 h later， from which the serum was collected for measurement of the D-xylose content. The serum， hippocampus， and colorectum samples of rats were collected on day 29. The levels of gastrin （GAS）， adrenocorticotropic hormone （ACTH）， corticosterone （CORT）， cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， interleukin （IL）-4， tumor necrosis factor （TNF）-α， and interferon （IFN）-γ in the serum and 5-hydroxytryptamine （5-HT） in the hippocampus were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was employed to reveal the colonic lesions. The mRNA and protein levels of p38 mitogen-activated protein kinase （MAPK）， extracellular signal-regulated kinase （ERK）， and c-Jun N-terminal kinase （JNK） in the colon tissue were determined by Real-time PCR and Western blot， respectively. ResultCompared with the normal group， the model group showed decreased body weight， anal temperature， and D-xylose content in the serum and increased GAS content （P<0.01）. The modeling led to cAMP/cGMP unbalance and decreased the ACTH and CORT content in the serum （P<0.01）， the preference for sucrose water， and the 5-HT content in the hippocampus （P<0.01）. Moreover， it shortened the colorectal length and caused massive infiltration of inflammatory cells and severe structural damage in the colon tissue. High， medium， and low doses of SSW&TXYF improved above indicators （P<0.05， P<0.01）， reduced inflammatory infiltration， and repaired the pathological damage of the tissue. Compared with the normal group， the model group showed lowered IL-4 level （P<0.01） and elevated TNF-α and IFN-γ levels （P<0.05， P<0.01） in the serum， as well as up-regulated expression of p38 MAPK， ERK， and JNK （P<0.05， P<0.01）. Compared with the model group， SSW&TXYF elevated the IL-4 level （P<0.01）， lowered the TNF-α and IFN-γ levels （P<0.05， P<0.01）， and down-regulated the mRNA and protein levels of p38 MAPK， ERK， and JNK （P<0.05， P<0.01）. ConclusionA rat model of UC with spleen-kidney Yang deficiency and liver depression was successfully established. SSW&TXYF can significantly mitigate this syndrome by reducing the inflammatory response in the colon and inhibiting the MAPK pathway.

Clinical analysis of 12 cases of invasive Klebsiella pneumoniae liver abscess syndrome / 中华全科医师杂志

Objective:To analyze the clinical features of patients with invasive Klebsiella pneumoniae liver abscess syndrome (IKLAS). Methods:The clinical data of 12 patients diagnosed as IKLAS in Zhuzhou Central Hospital from January 2020 to January 2023 were retrospectively analyzed.Results:Among 12 patients there were 6 males and 6 females with an mean age of 65.3±12.2 years (49-90). Nine patients were complicated with type 2 diabetes. The main clinical manifestations were fever ( n=9), chill ( n=6), shiver ( n=4), nausea and vomiting ( n=2), upper abdominal pain ( n=2), fatigue and anepithymia ( n=2), cough and expectoration ( n=1), disturbance of consciousness ( n=1) and hemoptysis ( n=1). The leukocyte count was increased in 8 cases, lymphocyte count decreased in 10 cases, and platelets count decreased in 3 cases. C-reactive protein and procalcitonin levels were elevated, while serum albumin levels were lowered in all patients. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were increased in 7 cases each. Liver abscess was located in the right lobe in 8 cases, in the left lobe in 1 cases, and in both lobes in 3 cases. There were 7 patients with single abscess, and 5 patients with multiple abscesses. The etiology was confirmed by liver pus culture ( n=10) and blood culture ( n=5), respectively. The main sites of invasion were lung and blood stream ( n=10 and n=5, respectively). The majority of Klebsiella pneumoniae isolates were antibiotic sensitive strains and the overall drug resistance rate was relatively low. All patients were given antibiotics, and 10 of them also received liver abscess puncture drainage. After treatment, 11 patients were discharged, and 1 died of septic shock. Conclusions:Patients with IKLAS exhibit diverse clinical symptoms, most patients are complicated with diabetes, and the main sites of invasion are in the lungs and blood stream. Timely diagnosis, active screening of extrahepatic infection sites, effective drainage of abscess and appropriate antibiotic treatment can improve the survival of patients.

Factors associated with acute rejection after pediatric kidney transplantation: a single-center cohort study / 中华器官移植杂志

Objective:To summarize the incidence of acute rejection (AR) after pediatric kidney transplantation (KT) at a single center and examine its impact on graft/patient survival and risk factors for AR.Methods:This is a retrospective cohort study including pediatric recipients who underwent kidney transplantation in past 8 years.After excluding recipients of graft thrombosis within a week post-transplant and lost to follow-ups, a total of 143 cases were ultimately recruited and assigned into two groups of AR (n=29) and non-AR (n=114).Basic profiles of both donors and recipients and graft/patient survival rate were compared between two groups.Relative risk factors for AR episodes were also examined by Logistic regression.Results:Renal grafts for 130/143 cases (90.9%) were harvested from deceased donors and 120(83.9%) cases from children.Twenty-seven transplants (18.9%) were performed in infants and young recipients aged < 3 years.During a median follow-up of 33 months, 34 AR episodes occurred in 29(20.3%) patients.Rate of re-transplantation (27.6% vs. 7.9%), pediatric donor (96.5% vs. 80.7%) and rabbit anti-human thymocyte globulin (rATG) induction (79.3% vs. 36%) were significantly higher in AR group than non-AR group ( P=0.007, P=0.046, P<0.001).Multivariate regression analysis indicated that basiliximab induction caused a significant reduction in the risk of AR incidence as compared with rATG induction (odds ratio 0.13, 95% confidence interval 0.04-0.43, P<0.001).The median time of AR incidence was 1.3 months post-transplantation and 23 episodes (67.6%) were confirmed by biopsy.After anti-rejection treatment, 52.9%(n=18) of the cases achieved a full recovery and 38.3% (n=13) had improved graft function.However, 3 cases (8.8%) developed irreversible graft failure.The 1/3-year graft survival rates were significantly lower in AR group than those in non-AR group (75.3% vs. 95.2%, 68.4% vs. 90.4%, P=0.01), and there was no significant difference in 1-and 3-year patient survival rates between two groups. Conclusions:The incidence of AR is relatively high in pediatric renal transplantation, which has an impact on graft survival.Basiliximab induction can effectively reduce the risk of AR.

De novo donor specific antibody mediated rejection in a child after kidney transplant / 中华器官移植杂志

One case of de novo donor specific antibody(dnDSA)mediated rejection after pediatric kidney transplantation(KT)was analyzed retrospectively.The risk factors and prevention procedures associated with dnDSA induction, and the clinical features and protocols for late post-transplant antibody-mediated rejection(AMR)in pediatric patients were presented.

Risk factors of pancreatic fistula after pancreaticoduodenectomy and pancreaticojejunostomy / 中华肝胆外科杂志

Objective:To analyze the risk factors of clinically-relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD) and penetrating pancreaticojejunostomy (PPJ).Methods:The clinical data of 108 patients who underwent PD and PPJ in the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Wannan Medical College from January 2017 to October 2022 were analyzed retrospectively, including 65 males and 43 females, aged 65.5 (54.2, 72.0) years. The incidences of POPF, biliary fistula, abdominal bleeding and other related complications were reviewed. The related factors of CR-POPF were analyzed by univariate analysis, and the statistically significant factors were included in multivariate logistic regression analysis.Results:A total of 108 patients were successfully treated with PD, including laparoscopic PD in 76 cases (70.4%) and open PD in 32 cases (29.6%). PPJ was performed in PD, including the continuous fashion in 39 cases (36.1%), intermittent fashion in 49 cases (45.4%) and modified continuous fashion in 20 cases (18.5%). The operation time was 390.0 (314.0, 480.0) min, the intraoperative blood loss was 200.0 (100.0, 384.0) ml, the postoperative hospital stay was 12.0 (10.0, 15.0) d, and the incidence of POPF (grade B + C) was 11.1% (12/108). Body mass index, pancreatic CT value and pancreatic duct size were the significant factors of CR-POPF (all P<0.05). Multivariate logistic regression analysis showed that age ( OR=0.895, 95% CI: 0.822-0.975), pancreatic CT value ( OR=0.812, 95% CI: 0.698-0.946) and pancreatic duct size ( OR=0.457, 95% CI: 0.220-0.952) were risk factors of CR-POPF after PPJ (all P<0.05). Conclusion:PPJ is a safe method of pancreaticoenterostomy, and CR-POPF may be related to younger patients, lower pancreatic CT value and the smaller pancreatic duct size.

Clinical significance of Autotaxin in primary biliary cholangitis and primary Sjogren′s syndrome / 中华风湿病学杂志

Objective:Primary biliary cholangitis (PBC) and Primary Sj?gren′s syndrome (pSS) are autoimmune epithelial inflammatory diseases that share many common clinical symptoms. The aim of this study was to investigate the differences and diagnostic value of Autotaxin (ATX) in PBC and SS.Methods:The clinical data of 237 cases diagnosed with PBC, PBC secondary to SS, pSS and healthy individuals(HC) between September 2020 and September 2021 were retrospectively analyzed. The levels of ATX in each group were measured by enzyme-linked immunosorbent assay (ELISA), and the corresponding sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve ( AUC), etc were analyzed. Normally distributed data were expressed as mean ±SD and non-normally distributed as median (IQR). The differences and correlations between ATX and the biochemical tests in each group were assessed by applying the Mann-Whitney U test, Spearman correlation analysis, etc. P<0.05 was considered statistically significant difference. Results:The results showed that ATX was positive in 33.9%, 33.3% and 53.3% for PBC, PBC secondary SS, and pSS, respectively, with the specificities of 93.1%, 100% and 93.2%, respectively. The highest accuracy was achieved in pSS and the sensitivity and specificity were 86.5% and 93.2%, which were higher than those in PBC group(56.8%, 93.1%), respectively. Compared with HC [32.6(21.8, 60.5)ng/ml], ATX levels in PBC[59.3(48.6, 86.3)ng/ml, U=1 750.50, P<0.001], PBC-SS [73.6 (53.3,102.4)ng/ml; U=199.00, P<0.001], and pSS [152.6 (97.4,192.1)ng/ml, U=264.00, P<0.001] were elevated with significant difference ( P<0.05). ATX levels showed a decreasing trend from the pSS group to the HC group. ATX in PBC group[AUC(95% CI)= 0.73(0.651,0.812), P<0.001], PBC secondary SS group [AUC(95% CI)=0.82(0.730, 0.912), P<0.001], and pSS group [AUC(95% CI)=0.94(0.898, 0.984), P<0.001] had prediction accuracy. ATX was associated with total protein ( r=-0.31, P=0.041) level and glutaminase (r=-0.26, P=0.024) level. Conclusion:ATX has diagnostic value in both PBC and SS, and with higher sensitivity and specificity for the latter.

Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults (version 2023) / 中华创伤杂志

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

Clinical guideline for diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture (version 2023) / 中华创伤杂志

Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.

White Matter Damage in Major Depressive Disorder and TCM Treatment： A Review / 中国实验方剂学杂志

At present， major depressive disorder （MDD） is highly prevalent with advanced neurological disorders as the main pathological manifestations. As the physiological function bearer of higher neural activity， gray matter has become the focus of MDD treatment. However， recent research has shown that white matter and gray matter are independent of each other in the central nervous system （CNS）， and their functions are integrated and linked. In addition to gray matter damage， white matter damage is also the core driving event of disease progression and determines the outcome of MDD. At the treatment level， the current drug treatment of MDD mainly focuses on gray matter repair， while ignoring the importance of white matter integrity for the treatment of the disease， which has become the weakness of the current treatment of MDD. Traditional Chinese medicine （TCM） has good application potential in white matter repair. This paper elaborated on the following three aspects. ① The roles of white matter damage in the occurrence and development of MDD were summarized. ② The key link of white matter repair in MDD was elaborated with microglia microenvironment regulation as the entry point. ③ The application value of TCM in white matter repair in MDD was analyzed. This review aims to highlight the importance of white matter integrity in the treatment of MDD and is expected to expand the understanding dimension of the activity of related Chinese medicines in MDD from the perspective of white matter repair and analyze its potential application value.

Expressions and clinical significance of ZEB1, AR, E-Ca and N-Ca in prostate cancer / 现代泌尿外科杂志

【Objective】 To analyze the correlation between the expressions of ZEB1, androgen receptor (AR), E-cadherin (E-Ca), N-cadherin (N-Ca) and clinicopathological features of prostate cancer patients with different risk levels, and to explore their significance. 【Methods】 The clinical data of 47 patients with prostate cancer treated during Nov.2013 and Jun.2021 were retrospectively analzyed. The patients were divided into medium-low risk group and high-risk group. The expressions of ZEB1, AR, E-Ca and N-Ca in the prostate cancer tissues of the two groups were detected with immunohistochemical staining. The relationship between the expressions and Gleason grade, prostate-specific antigen (PSA) level and TNM stage was analyzed. 【Results】 The positive expression rate of ZEB1 increased with higher risk, Gleason score, and PSA level (P<0.01); the strong positive expression rate of AR decreased with higher risk and Gleason score (P<0.05); the positive expression rate of E-Ca decreased with increased risk, Gleason score, and PSA level (P<0.05); the positive expression rate of N-Ca increased with the increased risk and Gleason score (P<0.01); the positive expression rate of ZEB1 increased with higher tumor stage and TNM stage (all P<0.01); the strong positive expression rate of AR decreased only with increased TNM stage (P<0.05). Patients whose first surgical specimen showing a higher expression level of ZEB1 were more likely to develop into castration-resistant prostate cancer CRPC (P<0.05). 【Conclusion】 ZEB1 and N-Ca levels increase with increased tumor aggressiveness, while AR and E-Ca levels decrease. ZEB1, AR, E-Ca and N-Ca play important roles in prostate cancer progression. ZEB1 can not only affect prostate cancer through epithelial stromal transformation (EMT), but also through AR. ZEB1 may also be related to the development of CRPC.

Clinical Analysis of Colistin Sulfate in the Treatment of Hematonosis Infected by Multidrug-Resistant Gram-Negative Bacteria / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of colistin sulfate in the treatment of hematonosis patients infected by multidrug-resistant (MDR) gram-negative bacteria (GNB), and discuss the possible factors that affect the efficacy of colistin sulfate.@*METHODS@#The clinical data of 85 hematologic patients infected with MDR GNB in the Soochow Hopes Hematonosis Hospital from April 2022 to November 2022 were collected and divided into clinically effective group with 71 cases and ineffective group with 14 cases according to the therapeutic efficacy of colistin sulfate. The age, gender, type of hematologic disease, status of hematopoietic stem cell transplantation, infection sites, type of pathogen, timing of administration, daily dose and duration of colistin sulfate, and combination with other antibacterial agents of patients in two groups were compared. Logistic regression was used to analyze on the meaningful variables to study the influencing factors of colistin sulfate. The adverse reactions of colistin sulfate were also evaluated.@*RESULTS@#There were no significant differences in age, gender, type of hematologic disease, hematopoietic stem cell transplantation status, infection sites and pathogen type between the effective group and the ineffective group (P>0.05). Compared with the medication time more than 7 days, meropenem used within 7 days in the clinical effective group, and timely replacement with colistin sulfate could obtain better efficacy, the difference was statistically significant (P=0.018). The duration of tigacycline before colistin sulfate did not affect the efficacy, and there was no significant difference in efficacy between the effective and ineffective groups. The therapeutic effect of colistin sulfate at daily dose of 500 000 U q8h was better than that of 500 000 U q12h, the difference was statistically significant (P=0.035). The time of colistin sulfate use in the clinically effective group was longer than that in the ineffective group, which had a statistical difference (P=0.003). Compared with the clinical ineffective group, the efficacy of combination regimens with colistin sulfate was better than that of colistin sulfate monotherapy, and the difference was statistically significant (P=0.013). Multivariate logistic regression analysis was performed on the indicators with statistical differences in the two groups of patients, which suggested that the use time of colistin sulfate (B: 2.358; OR: 10.573; CI: 1.567-71.361; P=0.015) and the combination of colistin sulfate (B: 1.720; OR: 5.586; CI: 1.210-25.787; P=0.028) were influential factors in the efficacy of colistin sulfate. During the treatment, the incidence of nephrotoxicity, hepatotoxicity and peripheral neurotoxicity were 5.9%, 1.2% and 1.2%, respectively.@*CONCLUSION@#The use of colistin sulfate improves the clinical efficacy of MDR GNB infections in hematological patients, and the timing of colistin sulfate administration and the combination of drugs are independent factors affecting its clinical efficacy, and the safety during treatment is high.

Four Properties of Chinese Herbal Medicine： A Review / 中国实验方剂学杂志

The four properties of Chinese herbal medicine have a history of several thousand years and are one of the important theoretical guides for the clinical application of Chinese herbal medicine. However， there have been few reviews of research methods and techniques for the four properties of Chinese herbal medicine in recent years. Therefore， this article summarized the advances and techniques for the four properties of Chinese herbal medicine by screening relevant literature on the four properties of Chinese herbal medicine and clarifying the characteristics， advantages， and applicable objects of each technique， in order to provide references for in-depth research on the four properties in the future. Chinese databases such as China national knowledge infrastructure （CNKI）， Wanfang data， and VIP， as well as international databases including PubMed， Cochrane Library， and EMbase were searched for relevant literature on the four properties of Chinese herbal medicine. The advances， research objects， and research techniques involved in the literature were extracted， classified， and summarized. Currently， the research techniques for the four properties of Chinese herbal medicine mainly include six categories， i.e.， literature data research， network pharmacology， biothermodynamics， cell biology， proteomics， and metabolomics. The research hierarchy can be divided into micro-level， small-level， medium-level， and macro-level. The research objects used in each experimental study are different， mainly single Chinese herbal medicine， Chinese herbal monomers， targets， microbial communities， cells， mice， and rats. Different research techniques explain the four properties of Chinese herbal medicine from different dimensions， which overall indicate the material basis of the four properties of Chinese herbal medicine. In future research， the interpretation of the four properties of Chinese herbal medicine can be first located at the research hierarchy， then corresponding research techniques can be selected according to the research hierarchy， and research indicators can be determined to obtain research conclusions. This can help researchers of traditional Chinese medicine effectively carry out research design and perform related experiments on the four properties of Chinese herbal medicine.

Anti-oxidative Stress Effect and Mechanism of Huangqintang on Caco-2 Cells Through Nrf2 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo verify the anti-oxidative stress effect of Huangqintang based on the nuclear factor E2-related factor 2 （Nrf2） signaling pathway by using Caco-2 cells as a carrier and RNA interference （RNAi） technology with in vitro experiments. MethodThe Caco-2 cells in the logarithmic growth phase were transfected with siRNA to construct siRNA Caco-2 cells. After normal Caco-2 cells and siRNA Caco-2 cells were incubated with Huangqintang of different doses， RNA and protein were extracted. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expression of heme oxygenase-1 （HO-1）， NAD（P）H quinone oxidoreductase 1 （NQO1）， glutathione S-transferase （GST）， Kelch-like ECH-associated protein 1 （Keap1）， and Nrf2. Meanwhile， the activities of superoxide dismutase （SOD） and GSH-Px， as well as the expression levels of malondialdehyde （MDA） and reactive oxygen species （ROS）， were detected by the colorimetric method and the probe method. ResultCompared with the results in the normal group， only the 400 mg·L-1 Huangqintang group and the sulforaphane （SFN） group could reduce the content of ROS and MDA in Caco-2 cells （P<0.01）， while the activities of SOD and GSH-Px in the cells of the Huangqintang groups and the SFN group showed an upward trend. Furthermore， there were significant differences in the 400 mg·L-1 Huangqintang group/the SFN group and the normal group （P<0.01）. Meanwhile， the protein and mRNA expression levels of HO-1， GST， Keap1， NQO1， and Nrf2 showed an upward trend in all groups （P<0.05， P<0.01）. After transfection， compared with the normal group， the model group showed increased content of MDA and ROS， blunted activities of GSH-Px and SOD， and reduced protein and mRNA expression of HO-1， GST， Keap1， and NQO1 （P<0.05， P<0.01）. After drug incubation， compared with the model group， the SFN group showed potentiated SOD activity， and the SFN group and the Huangqintang groups showed enhanced GSH-Px activity （P<0.01）. Moreover， the activities of SOD and GSH-Px in the 400 and 200 mg·L-1 Huangqintang groups and the SFN group showed an upward trend （P<0.01）， and the content of MDA in the 400 mg·L-1 Huangqintang group and the SFN group showed a downward trend. ROS decreased in all groups with drug intervention （P<0.01）， and the protein and mRNA expression of HO-1， GST， Keap1， NQO1， and Nrf2 increased to varying degrees （P<0.05， P<0.01）. ConclusionHuangqintang can play an anti-oxidative stress role by regulating the Nrf2 pathway.

Anti-inflammatory Effect of Huangqintang on LPS-induced RAW264.7 Inflammatory Cells / 中国实验方剂学杂志

ObjectiveTo explore the anti-inflammatory mechanism of Huangqintang based on the inflammation model in RAW264.7 cells. MethodHuangqintang was prepared and the safe dose to RAW264.7 cells was screened out. The RAW264.7 cells were seeded in 24-well plates and incubated with Huangqintang and lipopolysaccharide （LPS）， successively. The concentrations of nitric oxide （NO）， interleukin （IL）-6， tumor necrosis factor （TNF）-α， and prostaglandin E2 （PGE2） were measured by Griess assay and enzyme-linked immunosorbent assay （ELISA）， respectively. Meanwhile， RAW264.7 cells were inoculated in 6-well plates， and normal group， LPS group， LPS+Huangqintang group， nuclear factor-κB （NF-κB） p65 inhibitor PDTC group， p38 mitogen-activated protein kinase （MAPK） inhibitor SB203580 group， extracellular signal-regulated kinase （ERK） inhibitor PD98059 group， c-Jun N-terminal kinase （JNK） inhibitor SP600125 group， and Janus kinase （JAK） inhibitor AG490 group were set up. After the cells were incubated with corresponding inhibitors and Huangqintang and stimulated by LPS， RNA and protein were extracted. The mRNA and protein expression levels of NF-κB p65， p38 MAPK， ERK， JNK， and JAK were detected by Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively， to explore the anti-inflammatory mechanism of Huangqintang by regulating the NF-κB， MAPK， and JAK/signal transducer and activator of transcription protein （STAT） signaling pathways. ResultAfter stimulation with LPS， the concentrations of NO， IL-6， TNF-α， and PGE2 in the cells of the model group increased significantly（P<0.05，P<0.01）. Compare with the model group， after incubation with Huangqintang， the secretion of NO， IL-6， TNF-α， and PGE2 showed a downward trend （P<0.05，P<0.01）. Compared with the normal group， the model group showed increased mRNA expression of p38 MAPK， ERK， JNK， JAK， and NF-κB p65 and total protein expression in cells after stimulation with LPS （P<0.05，P<0.01）. Compare with the model group，after incubation with Huangqintang， the total protein and mRNA expression of p38 MAPK， ERK， JNK， JAK， and NF-κB p65 in inflammatory cells decreased （P<0.05，P<0.01）. Meanwhile， the expression of NF-κB p65 total protein and mRNA in each inhibitor group showed a downward trend （P<0.05，P<0.01）. ConclusionHuangqintang can inhibit the inflammatory response through the NF-κB， MAPK， and JAK-STAT signaling pathways.

Effect of Huangqintang on Intestinal Flora in Mice with Ulcerative Colitis and Its Protective Mechanism on Intestinal Mucosal Barrier / 中国实验方剂学杂志

ObjectiveTo evaluate the pharmacodynamic effect of Huangqintang （HQT） on ulcerative colitis （UC） model mice and investigate its protective effect against UC by regulating intestinal flora. MethodMale Balb/c mice were randomly divided into control group，model group， high-， medium-， and low-dose HQT groups （20， 10， 5 g·kg-1）， flora interference group， flora interference model group， and flora interference-drug treatment group （HQT， 20 g·kg-1）. The flora interference model was constructed through intragastric administration of antibiotics （200 mg·kg-1 bacitracin and 200 mg·kg-1 vancomycin） for 8 d， and the UC model was constructed by allowing mice with free access to 3% dextran sulfate sodium （DSS） solution for 7 d. HQT was administered for 7 d. After the experiments， the mice were sacrificed， and blood， colon， and feces were collected. Hematoxylin-eosin （HE） staining was performed to observe the colonic lesions. The serum levels of interleukin （IL）-4， IL-6， IL-10， and tumor necrosis factor （TNF）-α were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression of Claudin1， MUC1， Occludin， and zonula occludens-1（ZO-1） in colon tissues was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The fecal DNA of mice was extracted and analyzed by high-throughput sequencing. ResultCompared with the normal group， the model group showed increased serum content of IL-4， IL-6， and TNF-α （P<0.05， P<0.01） and decreased IL-10 （P<0.05）. Compared with the model group， the HQT groups displayed decreased serum levels of IL-4， IL-6， and TNF-α （P<0.05， P<0.01）， increased IL-10 content （P<0.01）， increased mRNA and protein expression levels of Claudin1， MUC1， Occludin， and ZO-1 （P<0.05， P<0.01）. After flora interference， the diversity and abundance of intestinal bacteria decreased. To be specific， Proteobacteria increased （P<0.01）， and Firmicutes and Bacteroidetes decreased （P<0.01）. After UC induction by DSS， Bacteroidetes and Tenericutes decreased （P<0.05）. The high-， medium-， and low-dose HQT groups showed increased Bacteroidetes and Tenericutes （P<0.05， P<0.01） and decreased Firmicutes （P<0.05）. Additionally， the abundance of Lactobacillus， Lachnospiraceae NK4A136 group， Escherichia-Shigella， and Helicobacteris was positively proportional to the dose of HQT. ConclusionHQT can inhibit the inflammatory response of UC mice， restore the imbalance of intestinal flora， and repair the damaged intestinal mucosal barrier.