Research on Preparation Process and Quality Evaluation of Traditional Chinese Medicine Dispensing Granules and Its Consistency with Traditional Decoction： A Review / 中国实验方剂学杂志

Traditional Chinese medicine dispensing granules（TCMDGs）is the new type of decoction pieces with the development of modernization of TCM， which has received mixed opinions since its practical application. In 2021， the national departments issued Announcement on Ending the Pilot Work of TCMDGs， marking the end of the 28-year pilot work of TCMDGs， and eligible TCM enterprises can produce TCMDGs after filing. However， this does not mean that the preparation process， quality standard and efficacy research of TCMDGs have been developed and matured， on the contrary， there are still some problems that need to be solved and gradually improved. For example， in the production process， there are problems such as unclear， unified and non-standardized preparation parameters. In terms of quality control， there are some problems such as lack of producing area regulation， variety selection and processing specification. In terms of consistency evaluation with traditional decoction， there are problems such as unclear relationship between the chemical constituents and pharmacological effects of the two. Therefore， in view of some prominent problems of TCMDGs at present， this paper takes the published literature as the main data source and combines the specific requirements of the code or technical standards such as the 2020 edition of Chinese Pharmacopoeia， Publicity of the Unified Standard on the Varieties of TCMDGs， Quality Control and Standard Formulation Technical Requirements of TCMDGs. The production process of TCMDGs， the origin and variety of raw materials， the processing of decoction pieces， the quality control standard and the consistency evaluation of formula granules and traditional decoction were sorted out and visualized by literature mining， data analysis and list comparison. Based on the analysis results， the following suggestions were made. In terms of preparation process， the completeness and standardization of process parameters should be strengthened. In terms of quality evaluation， attention should be paid to the relationship between the authenticity， variety， processing and quality of medicinal materials. In the consistency evaluation of formula granules and traditional decoction， the deep difference and mechanism between TCMDGs and traditional decoction were discussed by combining structural Chinese medicine， quality marker（Q-Marker） theory and physicochemical characterization， so as to provide reference for the application and development of TCMDGs.

Effect of Medicinal and Edible Herbs in Colorectal Cancer Patients During Chemotherapy / 中国实验方剂学杂志

Malignant tumors are a major health problem in current society. With the improvement of people's living standards and the changes in diet structure， the development trend of gastrointestinal tumors in China is gradually similar to that in developed countries. The incidence and mortality of colorectal cancer （CRC） remain high in China. Although targeted therapy and immunotherapy have greatly improved the prognosis of patients in recent years， chemotherapy is still the main means in clinical practice. However， the adverse reactions of chemotherapy often seriously affect the quality of life of patients， and even lead to treatment interruption， thereby affecting the efficacy. Oral Chinese medicine shows unique advantages in enhancing efficiency and reducing toxicity in CRC patients during chemotherapy， but its poor drug experience not only makes it difficult for patients to take it consistently but also affects the popularization of Chinese medicine at this stage. Medicinal and edible herbs （MEHs） are an important part of Chinese medicine and they are mild， delicious， convenient， affordable， nutritious， and safe. Therefore， they may be more suitable for patients with CRC chemotherapy to adhere to treatment. However， their efficacy is often criticized by clinical practitioners. They are only used in the food and health products industry， and their role as Chinese medicines has not been fully utilized. This paper summarized the common traditional Chinese medicine （TCM） syndromes and treatment methods during CRC chemotherapy， sorted out the nature， flavor， meridian tropism， and efficacy of MEHs， and reviewed the modern pharmacological research results of MEHs by the method of literature statistics. This study finds that the nature， flavor， meridian tropism， and efficacy of MEHs are in good agreement with the common TCM syndromes and treatment methods during CRC chemotherapy. Moreover， many MEHs have the effects of resisting CRC and alleviating the adverse reactions of chemotherapy. Furthermore， the effectiveness and superior efficacy of MEHs in CRC chemotherapy are initially demonstrated from the theoretical level， but high-quality clinical evidence is still needed to support it. The present study discussed the efficiency-enhancing and toxicity-reducing effects and application advantages of MEHs in CRC patients during chemotherapy to provide references for the clinical promotion of MEHs.

PAI-1 genetic polymorphisms influence septic patients' outcomes by regulating neutrophil activity / 中华医学杂志(英文版)

BACKGROUND@#Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathophysiology of sepsis, but the exact mechanism remains debatable. In this study, we investigated the associations among the serum levels of PAI-1, the incidence of 4G/5G promoter PAI-1 gene polymorphisms, immunological indicators, and clinical outcomes in septic patients.@*METHODS@#A total of 181 patients aged 18-80 years with sepsis between November 2016 and August 2018 in the intensive care unit in the Xinhua Hospital were recruited in this retrospective study, with 28-day mortality as the primary outcome. The initial serum level of PAI-1 and the presence of rs1799768 single nucleotide polymorphisms (SNPs) were examined. Univariate logistic regression and multivariate analyses were performed to determine the factors associated with different genotypes of PAI-1, serum level of PAI-1, and 28-day mortality.@*RESULTS@#The logistic analysis suggested that a high serum level of PAI-1 was associated with the rs1799768 SNP of PAI-1 (4G/4G and 4G/5G) (Odds ratio [OR]: 2.49; 95% confidence interval [CI]: 1.09, 5.68). Furthermore, a high serum level of PAI-1 strongly influenced 28-day mortality (OR 3.36; 95% CI 1.51, 7.49). The expression and activation of neutrophils (OR 0.96; 95% CI 0.93, 0.99), as well as the changes in the expression patterns of cytokines and chemokine-associated neutrophils (OR: 1.00; 95% CI: 1.00, 1.00), were both regulated by the genotype of PAI-1.@*CONCLUSIONS@#Genetic polymorphisms of PAI-1 can influence the serum levels of PAI-1, which might contribute to mortality by affecting neutrophil activity. Thus, patients with severe sepsis might clinically benefit from enhanced neutrophil clearance and the resolution of inflammation via the regulation of PAI-1 expression and activity.

Homocysteine and serum uric acid levels in type 2 diabetic retinopathy and their predictive value for disease / 中华眼底病杂志

Objective:To observe the correlation between homocysteine (Hcy) and serum uric acid (SUA) and retinopathy in type 2 diabetes mellitus (T2DM), preliminary study on its predictive value.Methods:A retrospective study. From January 2020 to March 2021, a total of 324 T2DM patients hospitalized in Department of Endocrinology, Cangzhou Central Hospital of Hebei Province were included. Fasting blood glucose (FBG), glycated hemoglobin (HbA1C), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), serum creatinine (Scr), blood urea nitrogen (BUN), Hcy, SUA, peripheral blood endothelial progenitor cells (EPC), circulating endothelial cells (CEC) were counted and homeostasis model assessment for insulin resistance (HOMA-IR) was calculated. According to the absence or presence of diabetic retinopathy (DR), the patients were divided into non DR (NDR) group and DR group with 100 and 214 cases, respectively. Clinical data and laboratory biochemical indexes of the two groups were compared and observed. The logistic regression was used to analyze the independent risk factors for DR in T2DM patients. Smooth curve fitting was used to analyze the curve relationship between Hcy, SUA and DR, and ROC area (AUC) of Hcy, SUA; their combined prediction of DR in T2DM patients was calculated by receiver operating characteristic curve (ROC curve), and the predictive value of Hcy and SUA for DR in T2DM patients was evaluated.Results:Diabetic course ( t=5.380), systolic blood pressure ( t=2.935), hypertension ( χ2=10.248), diabetic nephropathy ( χ2=9.515), diabetic peripheral neuropathy ( χ2=24.501), FBG ( t=3.945), HbA1C ( t=3.336) and TG in DR Group ( t=2.898), LDL-C ( t=3.986), Scr ( t=2.139), SUA ( t=7.138), HOMA-IR ( t=3.237), BUN ( t=3.609), Hcy ( t=2.363) and CEC ( t=19.396) were significantly higher than those in NDR group. The difference was statistically significant ( P<0.05). EPC ( t=9.563) and CPC ( t=7.684) levels were significantly lower than those of NDR group, and the difference was statistically significant ( P<0.05). Logistic regression analysis showed that diabetes course, SBP, hypertension, FBG, HbA1C, LDL-C, SUA, Hcy, EPC, CPC and CEC were all independent risk factors for developing DR in T2DM patients ( P<0.05). The smooth curve fitting analysis showed that Hcy and SUA were positively correlated with the occurrence of DR. After adjusting for confounding factors, when Hcy≥15 μmol/L, the risk of DR Increased by 14% for every 1 μmol/L increase in Hcy [odds ratio ( OR)=0.92, 95% confidence interval ( CI) 0.88-0.98, P<0.05]. When Hcy <15 μmol/L, there was no significant difference ( OR=0.96, 95% CI 0.92-1.08, P>0.05). When SUA≥304 μmol/L, the risk of DR increased by 17%, every 20 μmol/L SUA increased ( OR=0.80, 95% CI 0.68-0.94, P<0.05). When SUA <304 μmol/L, the difference was not statistically significant ( OR=0.83, 95% CI 0.72-0.95, P>0.05). ROC curve analysis results showed that the AUC values of Hcy, SUA and Hcy combined with SUA in predicting the occurrence of DR in T2DM patients were 0.775 (95% CI 0.713-0.837, P<0.001), 0.757 (95% CI 0.680-0.834, P<0.001) and 0.827 (95% CI 0.786-0.868, P<0.001). Hcy combined with SUA showed better predictive efficiency. Conclusions:The abnormal increase of Hcy and SUA levels in T2DM patients are closely related to the occurrence of DR, they are independent risk factors for the occurrence of DR. Hcy combined with SUA has high predictive value for the occurrence of DR.

Clinical effects of α-lipoic acid combined with epalrestat in elderly patients with diabetic peripheral neuropathy / 中华老年医学杂志

Objectives To examine the clinical effects of α-lipoic acid(ALA)combined with epalrestat in elderly patients with diabetic peripheral neuropathy(DPN)and its influence on plasma levels of high-sensitivity C-reactive protein(hs-CRP)and homocysteine(Hcy).Methods A total of 120 DPN patients aged over sixty years were randomly divided into the control group and the treatment group with 60 cases in each group.The control group received 0.6 g ALA in 250 ml saline given by an intravenous drip once a day and the treatment group was additionally given 50 mg epalrestat orally three times a day.Both groups were treated for two weeks.Improvement in clinical symptoms,nerve conduction velocity,and peripheral blood levels of hs-CRP and Hcy were compared between the two groups before and after treatment.Results TSS scores of all items and the total scores of the two groups decreased after treatment,with greater margins seen in the treatment group than in the control group(each P＜0.05).NCV increased in both groups after treatment (each P＜ 0.05),with greater increase in the treatment group(each P＜0.05).Levels of hs-CRP and Hcy were significantly reduced (each P＜0.05).A statistically significant difference was observed in hs-CRP(t =2.620,P=0.010) but not in Hcy(t =0.380,P =0.700)between the two groups.Conclusions ALA combined with epalrestat can significantly improve the symptoms of patients with DPN,with better outcomes than ALA alone,and effectively decrease the peripheral blood level of hs-CRP.

Screening and Identification of Antigenic Proteins from the Hard Tick Dermacentor silvarum (Acari: Ixodidae)

In order to explore tick proteins as potential targets for further developing vaccine against ticks, the total proteins of unfed female Dermacentor silvarum were screened with anti-D. silvarum serum produced from rabbits. The results of western blot showed that 3 antigenic proteins of about 100, 68, and 52 kDa were detected by polyclonal antibodies, which means that they probably have immunogenicity. Then, unfed female tick proteins were separated by 12% SDS-PAGE, and target proteins (100, 68, and 52 kDa) were cut and analyzed by LC-MS/MS, respectively. The comparative results of peptide sequences showed that they might be vitellogenin (Vg), heat shock protein 60 (Hsp60), and fructose-1, 6-bisphosphate aldolase (FBA), respectively. These data will lay the foundation for the further validation of antigenic proteins to prevent infestation and diseases transmitted by D. silvarum.

The effects of exogenous hydrogen sulfide on injury of rat hippocampus neurons induced by oxygen-glucose deprivation and restoration / 中华急诊医学杂志

Objective To investigate the effects of exogenous hydrogen sulfide (H2S) on injury of rat hippocampus neurons induced by oxygen-glucose deprivation and restoration (OGD/R) and explore its mechanism.Methods Hippocampus neurons were isolated from embryonic day 16-18 (E16-18) rat embryos.Hippocampus was immediately removed and digested with 0.25％ trypsin.The neurons were isolated and cultured at 37 ℃ for 7 days and neuron-specific enolase (NSE) was detected by immunohistochemical staining method to identify neurons.At 8th day,the neurons were placed in deoxygenated glucose-free medium and exposed to 95％ N2-5％ CO2 in an air tight chamber for 1 hour,and then replaced the glucose-free medium with original medium,and returned the cultures to a standard incubator in 5％ CO2 at 37 ℃ and incubated for another 24 h.The neurons were divided into 3 groups:group Ⅰ control; group Ⅱ OGD/R,and group ⅢOGD + NaHS,the latter was further divided into 5 subgroups:groups Ⅲ1-5 with 25,50,100,200,400 μmol/L NaHS added,respectively.Then cell viability was quantified by MTT method,the level of lactate dehydrogenase (LDH) were detected,apoptosis was measured by Annexin V FITC/PI Apoptosis Kits,and RT-PCR was used to assay HIF-1 α mRNA in neurons in all groups.Results Compared with control group,the LDH level,apoptosis and expression of HIF-1α mRNA in group Ⅱ were significantly increased,the cell viability was significantly decreased (P ＜ 0.01).There were no significant differences in the LDH level,apoptosis and expression of HIF-1 α mRNA and the cell viability between group Ⅱ and group Ⅲ1 (P ＞ 0.05).Compared with group Ⅱ,the LDH level,apoptosis and expression of HIF-1α mRNA in group Ⅲ2-4 were significantly increased,the cell viability was significantly increased (P ＜ 0.01).Compared with group Ⅱ,the LDH level,apoptosis and expression of HIF-1 α mRNA in the group Ⅲ 5 were significantly decreased,the cell viability was significantly decreased (P ＜ 0.01).Conclusions H2S of low concentration has no significant effects on injury of rat hippocampus neurons induced by OGD/R.H2S of moderate doses can protect rat hippocampus neurons from OGD/R injury and H2S of high concentration can aggravate injury.The expression of HIF-1α mRNA in rat hippocampus neurons was increased after OGD/R,and the protective role of H2S is associated with increase in the expression of HIF-1α mRNA.

Effects of hydrogen sulfide on apoptosis of cardiomyocytes after cardiopulmonary resuscitation in a rat model / 中华急诊医学杂志

Objective To explore the effects of hydrogen sulfide (H2S) on apoptosis of cardiomyocytes after cardiopulmonary resuscitation (CPR) in rat models.Methods Forty-five male SD rats were randomly into sham group (n =15),CPR group (n =15) and NaHS group (n =15).Rats of CPR group and NaHS group were operated to induce cardiac arrest by transcutaneous electrical stimulation to epicardium.In NaHS group,NaHS (5 mg/kg) was administrated via the femoral venous line 1 min before CPR.Hemodynamic variables were monitored and obtained continuously.Survival rats were sacrificed at 24 h after restoration of spontaneous circulation and the hearts were removed for analysis by RT-PCR and TUNEL assays.Blood samples were collected and plasma content of cTnT was detected.Results Compared with the CPR group,animals treated with NaHS had improved left ventricular function (P ＜0.01),lower plasma cTnT levels (P ＜0.05) and decreased apoptosis index (P ＜ 0.01) 24 h after ROSC.The expressions of Caspase-3 mRNA,Bax mRNA and Bcl-2 mRNA in CPR group and NaHS group were higher compared with the control group (P ＜0.01).The NaHS group had lower expressions of Caspase-3 mRNA and Bax mRNA (P ＜0.01),but higher expression of Bcl-2 mRNA (P ＜0.05) compared with the CPR group.Conclusions Exogenous (H2S) regulated the expressions of Caspase-3,Bax and Bcl-2 mRNA,thereby preventing apoptosis of cardiomyocytes,inhibiting cTnT release and improving left ventricular function 24 h after CPR.

Gene Cloning, Expression and Immunogenicity of the Protective Antigen Subolesin in Dermacentor silvarum

Subolesin (4D8), the ortholog of insect akirins, is a highly conserved protective antigen and thus has the potential for development of a broad-spectrum vaccine against ticks and mosquitoes. To date, no protective antigens have been characterized nor tested as candidate vaccines against Dermacentor silvarum bites and transmission of associated pathogens. In this study, we cloned the open reading frame (ORF) of D. silvarum 4D8 cDNA (Ds4D8), which consisted of 498 bp encoding 165 amino acid residues. The results of sequence alignments and phylogenetic analysis demonstrated that D. silvarum 4D8 (Ds4D8) is highly conserved showing more than 81% identity of amino acid sequences with those of other hard ticks. Additionally, Ds4D8 containing restriction sites was ligated into the pET-32(a+) expression vector and the recombinant plasmid was transformed into Escherichia coli rosetta. The recombinant Ds4D8 (rDs4D8) was induced by isopropyl beta-D-thiogalactopyranoside (IPTG) and purified using Ni affinity chromatography. The SDS-PAGE results showed that the molecular weight of rDs4D8 was 40 kDa, which was consistent with the expected molecular mass considering 22 kDa histidine-tagged thioredoxin (TRX) protein from the expression vector. Western blot results showed that rabbit anti-D. silvarum serum recognized the expressed rDs4D8, suggesting an immune response against rDs4D8. These results provided the basis for developing a candidate vaccine against D. silvarum ticks and transmission of associated pathogens.

Screening and Molecular Cloning of a Protective Antigen from the Midgut of Haemaphysalis longicornis

Vaccination is considered a promising alternative for controlling tick infestations. Haemaphysalis longicornis midgut proteins separated by SDS-PAGE and transferred to polyvinylidene difluoride (PVDF) membrane were screened for protective value against bites. The western blot demonstrated the immunogenicity of 92 kDa protein (P92). The analysis of the P92 amino acid sequence by LC-MS/MS indicated that it was a H. longicornis paramyosin (Hl-Pmy). The full lenghth cDNA of Hl-Pmy was obtained by rapid amplification of cDNA ends (RACE) which consisted of 2,783 bp with a 161 bp 3' untranslated region. Sequence alignment of tick paramyosin (Pmy) showed that Hl-Pmy shared a high level of conservation among ticks. Comparison with the protective epitope sequence of other invertebrate Pmy, it was calculated that the protective epitope of Hl-Pmy was a peptide (LEEAEGSSETVVEMNKKRDTE) named LEE, which was close to the N-terminal of Hl-Pmy protein. The secondary structure analysis suggested that LEE had non-helical segments within an alpha-helical structure. These results provide the basis for developing a vaccine against biting H. longicornis ticks.

Common Pathogens in Burn Wards and Their Drug Resistance / 中华医院感染学杂志

OBJECTIVE To know the pathogens distribution and resistance situation in the burn wards.METHODS A retrospective analysis was conducted to 627 pathogen isolates and sensitivity results,which submitted by burn department from May 2005 to May 2008.RESULTS Gram-negative(G-) bacilli occupied for 33.8%,Gram-positive(G+) cocci occupied for 48.8% and fungi occupied for 17.4%.Acinetobacter baumannii occupied for 8.6%,Pseudomonas aeruginosa occupied for 6.0%,Staphylococcus aureus occupied for 77.5%,in which the isolation rate of meticillin-resistant S.aureus(MRSA) was 94.9%.The drug sensitivity tests showed that various detectable bacteria possessed multi-drug resistance;G+ bacteria were sensitive to vancomycin,G-were sensitive to imipenem,but only A.baumannii was sensitive to cefoperazone/sulbactam.CONCLUSIONS The bacterial infection in the burn department in our hospital mainly is due to G+ cocci,then is G-bacilli,from which the A.baumannii detection rate is increasing.Clinicians should enhence to detect the sensitivity of bacteria and use antibiotics reasonably.