OBJECTIVE To optimize the simmering technology of Rheum palmatum from Menghe Medical School and compare the difference of chemical components before and after processing. METHODS Using appearance score， the contents of gallic acid， 5-hydroxymethylfurfural （5-HMF）， sennoside A+sennoside B， combined anthraquinone and free anthraquinone as indexes， analytic hierarchy process （AHP）-entropy weight method was used to calculate the comprehensive score of evaluation indicators； the orthogonal experiment was designed to optimize the processing technology of simmering R. palmatum with fire temperature， simmering time， paper layer number and paper wrapping time as factors； validation test was conducted. The changes in the contents of five anthraquinones （aloe-emodin， rhein， emodin， chrysophanol， physcion）， five anthraquinone glycosides （barbaloin， rheinoside， rhubarb glycoside， emodin glycoside， and emodin methyl ether glycoside）， two sennosides （sennoside A， sennoside B）， gallic acid and 5-HMF were compared between simmered R. palmatum prepared by optimized technology and R. palmatum. RESULTS The optimal processing conditions of R. palmatum was as follows: each 80 g R. palmatum was wrapped with a layer of wet paper for 0.5 h， simmered on high heat for 20 min and then simmered at 140 ℃， the total simmering time was 2.5 h. The average comprehensive score of 3 validation tests was 94.10 （RSD＜1.0%）. After simmering， the contents of five anthraquinones and two sennosides were decreased significantly， while those of 5 free anthraquinones and gallic acid were increased to different extents； a new component 5-HMF was formed. CONCLUSIONS This study successfully optimizes the simmering technology of R. palmatum. There is a significant difference in the chemical components before and after processing， which can explain that simmering technology slows down the relase of R. palmatum and beneficiate it.

Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

Objective To develop a two-dimensional liquid chromatographic method for rifapentine blood concentration determination.Methods The blood concentration of rifapentine was determined by a novel two-dimensional liquid chromatography(2D-LC)with a one-dimensional column:Aston SC2T(3.5 mm ×50.0 mm,5 μm);a two-dimensional column:Aston SCB(4.6 mm ×250.0 mm,5 μm);the temperature of the column was 40 ℃;the flow rate was 1.0 mL·min-1;the detection wavelength was 335 nm;the injection volume was 300 μL.The specificity,standard curve and lower limit of quantification,precision and recovery,and stability of the method were investigated.The method was used to determine the blood concentration of rifapentine in tuberculosis patients.Results Rifapentine showed good linearity within 0.33-18.62 μg·mL-1 with the standard curve equation of y=2.68 x 105x-5 850.36(r=0.997),the recoveries were 99.81％-105.08％,and the intra-and inter-day precision were ≤4.84％.The results of rifapentine blood concentration measurements in tuberculosis patients were in the range of 0.10-54.70μg·mL-1,and 64.74％were within the therapeutic window concentration range(8-30 μg·mL-1).Conclusion The method is easy to operate,has high sensitivity,low detection limit and high specificity,and is suitable for clinical blood concentration determination.Individual differences in the administration of rifapentine in tuberculosis patients are large,and blood concentration monitoring is required for individualized treatment.

Objective To investigate the efficacy of roxallistat combined with polysaccharide iron complex and Shengxuening in the treatment of maintenance hemodialysis renal anemia with poor recombinant human erythropoiesis.Methods Maintenance hemodialysis renal anemia patients with poor recombinant human erythropoietin effect were divided into control group and treatment group according to random number table method.The control group took roxallistat orally with a body weight of＞60 kg,120 mg each time,3 times a week,and 45-60 kg with 100 mg each time,3 times a week;oral polysaccharide iron complex,300 mg each time,once a day.The treatment group was given Shengxuening orally based on the control group,0.25-0.50 g each time,3 times a day.Both groups were treated for 3 months.The clinical efficacy,inflammatory factors,iron metabolism,renal function,anemia index,traditional Chinese medicine symptom score and adverse drug reaction were compared between the two groups.Results In the control group,34 cases were enrolled,1 case fell off,and finally 33 cases were included in the analysis.In the treatment group,35 cases were enrolled,1 case was shed,and 34 cases were finally included in the analysis.After treatment,the total effective rate of treatment group and control group was 97.06％(33 cases/34 cases)and 81.82％(27 cases/33 cases),respectively,and the difference was statistically significant(P＜0.05).After treatment,the nuclear transcription factor kappa B(NK-κB)in treatment group and control group were(24.09±3.06)and(35.23±4.11)ng·L-1;interferon gamma(IFN-γ)were(41.39±4.13)and(50.10±5.27)ng·L-1;transferrin saturation(TAST)were(38.62±5.91)％and(31.16±4.73)％;serum ferritin(SF)were(28.13±5.77)and(22.47±4.65)μmol·L-1;serum iron(SI)were(15.66±3.76)and(13.19±2.94)μmol·L-1;urinary protein excretion rate(24 h UPE)were(1.85±0.41)and(2.91±0.62)g·24 h-1;blood urea nitrogen(BUN)were(5.16±0.67)and(6.89±0.97)mmol·L-1;hemoglobin(Hb)were(91.38±11.23)and(83.19±8.54)g·L-1;hematocrit(Hct)were(29.01±7.40)％and(24.56±5.69)％;main disease score were(5.29±1.05)and(7.15±1.53)scores;the secondary scores were(3.11±0.46)and(4.98±0.77)scores;the total scores were(8.40±1.49)and(12.13±2.30)scores,with statistical significance(all P＜0.05).The total incidence of adverse drug reactions in treatment group and control group were 14.71％and 9.09％,with no statistical significance(P＞0.05).Conclusion Roxallistat combined with polysaccharide and iron complex and Shengxuening have good therapeutic effect in the treatment of maintenance hemodialysis renal anemia with poor recombinant human erythropoietin effect;it can reduce inflammation,regulate iron metabolism,improve renal function,and reduce adverse drug reactions.

Objective To investigate the role of programmed necrosis pathway in testicular tissue damage in rats with erectile dysfunction(ED)and the mechanism of sildenafil intervention.Methods An ED rat model was established by high-fat chow feeding,and the rats were randomly divided into model group,experimental group,interleukin 18 group,and experimental+interleukin 18 group;10 rats were randomly selected as the normal control group.The experimental group was gavaged with 20 mg·kg-1sildenafil;the interleukin 18 group was injected intraperitoneally with 0.2 μg·kg-1interleukin 18 recombinant protein;the experimental+interleukin 18 group was gavaged with an equal amount of sildenafil,and the experimental+interleukin 18 group was injected intraperitoneally with an equal amount of interleukin 18 recombinant protein;the normal control and model groups were given with an equal amount of 0.9％NaCl by gavage and intraperitoneally injected with an equal amount of saline;and the experimental group was injected with an equal amount of 0.9％NaCl.Interleukin 18 group was gavaged with an equal amount of 0.9％NaCl,and the five groups of rats were administered once a day at regular intervals for 14 consecutive days.Reverse transcription polymerase chain reaction(RT-qPCR)and Western blotting were used to detect the expression of receptor-interacting protein kinase 1(RIP1),receptor-interacting protein kinase 3(RIP3),mixed-spectrum kinase structural domain-like protein(MLKL),and calcium-calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)in rat testis tissues.Results The relative expression levels of RIP1 protein in the normal control group,model group,experimental group,interleukin 18 group and experimental+interleukin 18 group were 0.58±0.05,0.99±0.09,0.71±0.05,1.23±0.07 and 0.81±0.07;the relative expression levels of RIP3 protein were 0.61±0.05,1.05±0.10,0.77±0.04,1.19±0.07 and 0.84±0.08,respectively;the relative expression levels of MLKL protein were 0.63±0.05,1.13±0.08,0.79±0.05,1.30±0.02 and 1.00±0.04,respectively;the relative expression levels of CaMK Ⅱ protein were 0.54±0.04,1.12±0.07,0.77±0.05,1.36±0.04 and 1.00±0.07;the differences of the above indexes were statistically significant when the model group was compared with the normal control group,the experimental group was compared with the model group,the interleukin 18 group was compared with the model group,and the experimental+interleukin 18 group was compared with the interleukin 18 group(all P＜0.05).Conclusion The RIP1/RIP3-mediated necroptosis pathway plays multiple regulatory roles in testicular injury in ED rats,and sildenafil may improve testicular function in rats by inhibiting the above necroptosis signaling pathway.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

OBJECTIVE To summarize and analyze the profile of the implementation of pharmaceutical service by community pharmacists for patients with chronic diseases in China. METHODS Literature was searched from CNKI， Wanfang database， PubMed （Medline）， Embase， and Scopus to collect studies about community pharmacists providing pharmaceutical services for patients with chronic diseases. The ways and contents of the implementation of pharmaceutical services for chronic diseases by community pharmacists were summarized descriptively. RESULTS A total of 75 studies were included， involving 49 trial studies and 26 cross-sectional studies. The study sites were mainly located in the developed regions of China， and the types of disease involved in the studies were mainly diabetes mellitus （n＝30） and hypertension （n＝28）； most studies used the following indexes to evaluate pharmaceutical services， such as changes in disease symptoms and related indicators（n＝35）， improvement of patient compliance（n＝34）， and the occurrence of adverse drug reactions （irrational drug use） （n＝25）. The pharmaceutical service provided by community pharmacists included medication education （84.0%）， monitoring and follow-up （64.0%）， and identifying and solving medication-related problems （58.7%）. Thirty-eight studies mentioned that pharmaceutical services were achieved through teamwork， 16 of which mentioned healthcare alliances. A few studies investigated stratified healthcare systems （n＝15） and internet-based pharmaceutical services （n＝10）. CONCLUSIONS In China， pharmaceutical services provided by community pharmacies for patients with chronic diseases are still mainly confined to economically developed areas， and the scope of services is limited to a few diseases and basic pharmaceutical practices. In the future， the implementation of precise pharmaceutical services for different diseases and patients’ disease status， the establishment of medical alliances， and the development of internet-based pharmaceutical services should become the focus of pharmaceutical services.

Objective:To explore the clinical application and triage management value of using blood circulating cell-free DNA (cfDNA) (cysteine dioxygenase type 1 gene, CDO1, and Homeobox protein A9 gene, HOXA9) hypermethylation level to detect and diagnose ovarian cancer.Methods:A case-control study was conducted on patients who went for surgery at Chengdu Womens and Childrens Central Hospital from November 2022 to October 2023. Blood samples were collected before surgery for evaluation of cancer antigen 125 (CA125), human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA) score, and DNA methylation testing. The basic clinical information, biomarkers, and transvaginal ultrasound (TVS) information were collected simultaneously. Information from a total of 151 patients was collected, including 122 cases with benign pathology and 29 ovarian cancer cases. The pathologic diagnosis of ovarian tissue was defined as the gold standard. The multivariate logistic regression analysis was used to identify high-risk factors for ovarian cancer. The clinical efficacy of DNA methylation detection for ovarian cancer was analyzed using the area under curve (AUC).Results:The results showed that the age, menopausal status, CA125 and HE4 detection, ROMA score, positivity rate of CDO1 gene and HOXA9 gene single or combined testing in ovarian cancer patients were higher than those in the benign group and showed significant differences ( P<0.05). Among these detection protocols, the AUC of CDO1 and HOXA9 dual gene methylation testing for ovarian cancer was the highest at 0.936 (95% CI, 0.878-0.994), with 89.7% (95% CI 73.6%-96.4%) sensitivity and 97.5% (95% CI 93.0%-99.2%) specificity, respectively. The positive detection rate of CDO1 and HOXA9 dual gene methylation in early ovarian cancer FOGO I-II stage is 12/14 higher than other tests. Conclusion:Blood cfDNA methylation detection, a simple, non-invasive, and highly sensitive detection method, is superior to the current ovarian cancer testing in the risk assessment and early detection.

ObjectiveIn recent years, with the intensification of environmental issues and the depletion of ozone layer, incidence of skin tumors has also significantly increased, becoming one of the major threats to people’s lives and health. However, due to factors such as high concealment in the early stage of skin tumors, unclear symptoms, and large human skin area, most cases are detected in the middle to late stage. Early detection plays a crucial role in postoperative survival of skin tumors, which can significantly improve the treatment and survival rates of patients. We proposed a rapid non-invasive electrical impedance detection method for early screening of skin tumors based on bioimpedance spectroscopy (BIS) technology. MethodsFirstly, we have established a complete skin stratification model, including stratum corneum, epidermis, dermis, and subcutaneous tissue. And the numerical analysis method was used to investigate the effect of dehydrated and dry skin stratum corneum on contact impedance in BIS measurement. Secondly, differentiation effect of different diameter skin tumor tissues was studied using a skin model after removing the stratum corneum. Then, in order to demonstrate that BIS technology can be used for detecting the microinvasion stage of skin tumors, we conducted a simulation study on the differentiation effect of skin tumors under different infiltration depths. Finally, in order to verify that the designed BIS detection system can distinguish between tumor microinvasion periods, we conducted tumor invasion experiments using hydrogel treated pig skin tissue. ResultsThe simulation results show that a dry and high impedance stratum corneum will bring about huge contact impedance, which will lead to larger measurement errors and affect the accuracy of measurement results. We extracted the core evaluation parameter of relaxed imaginary impedance (Z_imag-relax) from the simulation results of the skin tumor model. When the tumor radius (R_tumor) and invasion depth (h)>1.5 mm, the designed BIS detection system can distinguish between tumor tissue and normal tissue. At the same time, in order to evaluate the degree of canceration in skin tissue, the degree of tissue lesion (ε_worse) is defined by the relaxed imaginary impedance (Z_imag-relax) of normal and tumor tissue (ε_worse is the percentage change in virtual impedance of tumor tissue relative to that of normal tissue), and we fitted a Depth-Z_imag-relax curve using relaxation imaginary impedance data at different infiltration depths, which can be applied to quickly determine the infiltration depth of skin tumors after being supplemented with a large amount of clinical data in the future. The experimental results proved that when ε_worse=0.492 0, BIS could identify microinvasive tumor tissue, and the fitting curve correction coefficient of determination was 0.946 8, with good fitting effect. The simulation using pig skin tissue correlated the results of real human skin simulation with the experimental results of pig skin tissue, proving the reliability of this study, and laying the foundation for further clinical research in the future. ConclusionOur proposed BIS method has the advantages of fast, real-time, and non-invasive detection, as well as high sensitivity to skin tumors, which can be identified during the stage of tumor microinvasion.

The growth of three plague phages from Qinghai Plateau in two Yersinia pestis strains(plague vaccine strains EV76 and 614F)and four non-Yersinia pestis strains(Yersinia pseudotuberculosis PTB3,PTB5,Escherichia coli V517,and Yersinia enterocolitica 52302-2)were detected through a micromethod based on the OmniLogTM microbial identification system and by the drop method,to provide a scientific basis for future ecological studies and classification based on the host range.For plague vaccine strains EV76 and 614F,successful phage infection and subsequent phage growth were observed in the host bacte-rium.Diminished bacterial growth and respiration and a concomitant decrease in color were observed with the OmniLogTM mi-crobial identification system at 33 ℃ for 48 h.Yersinia pseudotuberculosis PTB5 was sensitive to Yersinia pestis phage 476,but Yersinia pseudotuberculosis PST5 was insensitive to phage 087 and 072204.Three strains of non-Yersinia pestis(Yersinia pseudotuberculosis PTB3,Escherichia coli V517,and Yersinia enterocolitica 52302-2)were insensitive to Yersinia pestis pha-ges 087,072204,and 476 showed similar growth curves.The growth of phages 476 and 087,as determined with the drop method,in two Yersinia pestis strains(plague vaccine strains EV76 and 614F)and four non-Yersinia pestis strains(Yersinia pseudotuberculosis PTB3,Escherichia coli V517,and Yersin-ia enterocolitica 52302-2)showed the same results at 37 ℃,on the basis of comparisons with the OmniLogTM microbial i-dentification system;in contrast,phages 072204 did not show plaques on solid medium at 37 ℃ with plague vaccine strains EV76 and 614F.Determination based on the OmniLogTM detection system can be used as an alternative to the traditional determination of the host range,thus providing favorable application val-ue for determining the interaction between the phage and host bacteria.