1.Research progress on strategies to target intestinal microbiota to improve drug resistance in tumor immunotherapy
Hui-ling LI ; Bi-qing LIU ; Ying-nan FENG ; Xin HU ; Lan ZHANG ; Xian-zhe DONG
Acta Pharmaceutica Sinica 2025;60(2):260-268
A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.
2.Syndrome Element Distribution and Complication Risks in Type 2 Diabetic Patients:A Retrospective Cross-Sectional Study
Yu WEI ; Lili ZHANG ; Ling ZHOU ; Linhua ZHAO ; Qing NI ; Xiaolin TONG
Journal of Traditional Chinese Medicine 2025;66(13):1363-1368
ObjectiveTo investigate the distribution of traditional Chinese medicine (TCM) syndrome elements in type 2 diabetes mellitus (T2DM) patients based on maximum body mass index (maxBMI) and explore their association with complication risks. MethodsA retrospective cross-sectional study was used to collect clinical data from hospitalized T2DM patients, extracting age, gender, smoking history, alcohol consumption history, duration of disease, HbA1c level, complications, and TCM syndromes, and extracting the syndrome elements of disease location and disease nature based on their TCM syndromes. MaxBMI was calculated by telephone survey of patients' self-reported maximum body weight; patients with maxBMI ≥24 kg/m2 were classified into spleen-heat syndrome group, and those with maxBMI <24 kg/m2 were classified into consumptive-heat syndrome group. The distribution of TCM syndrome types and syndrome elements of patients in the two groups were analysed. Then the propensity score matching method was used to balance the baseline characteristics between the two groups and compare the differences in the distribution of syndrome types and syndrome elements and the risk of macrovascular and microvascular complications between the two groups. ResultsAmong the 1178 T2DM patients, syndrome elements in spleen-heat patients (1034 cases) were primarily located in the spleen (351 cases, 33.95%), liver (240 cases, 23.21%), and stomach (139 cases, 13.44%), while in consumptive-heat patients (144 cases), they were concentrated in the spleen (57 cases, 39.58%), liver (34 cases, 23.61%), and kidneys (17 cases, 11.81%); regarding syndrome elements of disease nature, spleen-heat patients were predominantly characterized by qi deficiency (481 cases, 46.52%), phlegm (353 cases, 22.73%), and dampness (241 cases, 23.31%), whereas consumptive-heat patients showed more qi deficiency (84 cases, 58.33%) and yin deficiency (44 cases, 30.56%). After propensity score matching, 132 cases were included in each group, and no statistically significant differences were observed in the distribution of syndrome elements of disease location between the two groups (P>0.05), but the phlegm element was significantly more prevalent in spleen-heat patients than in consumptive-heat patients (P = 0.006). Regarding the risk of complications, spleen-heat patients had a significantly higher risk of developing macrovascular complications compared to consumptive-heat patients (OR=2.04, P=0.010), while no significant differences were found between groups in the occurrence of microvascular complications (P>0.05). ConclusionThe spleen-heat T2DM patients show a more frequent syndrome element of disease nature of phlegm, and a higher risk of developing macrovascular complications compared to consumptive-heat patients.
3.Establishment of Psoriasis Rat Model with Spleen Deficiency and Dampness Obstruction Syndrome Induced by External Dampness Factors
Yating ZHANG ; Haojie SU ; Fanlu LIU ; Panyu ZHOU ; Qing WANG ; Junhong ZHANG ; Jingjing WU ; Ling HAN
Journal of Traditional Chinese Medicine 2025;66(13):1369-1377
ObjectiveTo construct a rat model of psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type), and evaluate the macroscopic manifestations and microscopic indicators of the model. MethodsTwenty-two SD rats were divided into normal group (n=3), common psoriasis group (n=5), spleen deficiency and dampness obstruction syndrome (external dampness type) group (n=7), and psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group (n=7). The spleen deficiency and dampness obstruction syndrome (external dampness type) rat model was established through 32-week exposure to an artificially simulated high-humidity environment, while the common psoriasis model was developed via 7-day topical application of imiquimod cream, and these two approaches were combined to construct a composite model of psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type). Rats in the normal group were housed under normal humidity conditions. The general state, tongue manifestation of rats were observed to evaluate the macroscopic syndrome manifestations; the microscopic syndrome manifestations of rats were evaluated through adipose tissue and liver tissue changes; the severity of psoriasis in rats was evaluated through skin pathological changes, psoriasis area and severity index (PASI), proliferating cell nuclear antigen (PCNA) expression and spleen tissue changes; changes in rat CD4+ interferon-γ+ cells (CD4+IFN-γ+ cells), CD4+ tumour necrosis factor-α+ cells (CD4+ TNF-α+ cells), and forkhead framing protein P3+ regulatory T cells (CD3+CD4+FoxP3+ Treg cells) were detected by flow cytometry. ResultsMacroscopically, both the spleen deficiency and dampness obstruction syndrome (external dampness type) group and psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group exhibited manifestations of spleen deficiency and dampness obstruction, including lethargy, huddling behavior, dull and disheveled fur, as well as soft or loose stools and perianal soiling in some individuals; both these two groups displayed enlarged tongue, swollen, and moist tongue texture, accompanied by slippery tongue surface. Microscopically, compared to the common psoriasis group, the psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group showed increased epididymal fat index (P<0.05); compared to the normal group and spleen deficiency and dampness obstruction syndrome (external dampness type) group, the psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group demonstrated significantly elevated spleen mass (P<0.05), while hepatic gross morphology and HE staining revealed no significant histopathological changes across all groups. Dorsal skin lesions were markedly exacerbated in the psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group when compared to those in common psoriasis group. Both the common psoriasis group and psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group exhibited significantly higher erythema scores, scaling scores, infiltration scores, PASI total scores, and proportions of CD3+CD4+FoxP3+Treg cells compared to the normal group and spleen deficiency and dampness obstruction syndrome (external dampness type) group (P<0.05), with pronounced PCNA-positive expression observed in the epidermal basal layer and dermis; the psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) group displayed significantly increased proportions of CD4+TNF-α+cells compared to the spleen deficiency and dampness obstruction syndrome (external dampness type) group (P<0.05); whereas no significant differences were detected in CD4+IFN-γ+cell proportions among groups (P>0.05). ConclusionThe rat model of psoriasis with spleen deficiency and dampness obstruction syndrome (external dampness type) can be successfully constructed by artificially simulating a high-humidity environment combined with imiquimod induction.
4. Ligustilide delays senescence of auditory cortex in mice by inhibiting ferritinophagy
Ying-Dong ZHOU ; Meng-Xian ZHANG ; Qing-Ling WANG ; Hao-Ran KANG ; Zhi-Cheng ZHANG ; Xiang-Dong GUO ; Qing-Lin WANG ; Ya-Min LIU
Chinese Pharmacological Bulletin 2024;40(3):455-461
Aim To investigate the mechanism of ligu aged 2 months of the same strain were used as the constilide (LIG) in delaying the senescence of auditory trol (Ctrl) group. Auditory brainstem response test was cortex and treating central presbycusis. Methods used to detect the auditory threshold of mice before and Forty C57BL/6J mice aged 13 months were randomly di after treatment. Levels of serum MDA and activity of vided into ligustilide low-dose(L-LIG) group, ligustil serum SOD were detected to display the level of oxidative ide medium-dose (M-LIG) group, ligustilide high-dose stress. The pathological changes of auditory cortex were (H-LIG) group and aging (Age) group, and 10 mice observed by HE staining. Ferroptosis was observed by
5.Epidemiological Investigation of Dampness Syndrome Manifestations in the Population at Risk of Cerebrovascular Disease
Xiao-Jia NI ; Hai-Yan HUANG ; Qing SU ; Yao XU ; Ling-Ling LIU ; Zhuo-Ran KUANG ; Yi-Hang LI ; Yi-Kai ZHANG ; Miao-Miao MENG ; Yi-Xin GUO ; Xiao-Bo YANG ; Ye-Feng CAI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):531-539
Objective To make an epidemiological investigation on traditional Chinese medicine(TCM)dampness syndrome manifestations in the population at risk of cerebrovascular diseases in Guangdong area.Methods A cross-sectional study was conducted to analyze the clinical data related to the risk of cerebrovascular diseases in 330 Guangdong permanent residents.The diagnosis of dampness syndrome,quantitative scoring of dampness syndrome and rating of the risk of stroke were performed for the investigation of the distribution pattern of dampness syndrome and its influencing factors.Results(1)A total of 306(92.73%)study subjects were diagnosed as dampness syndrome.The percentage of dampness syndrome in the risk group was 93.82%(258/275),which was slightly higher than that of the healthy group(48/55,87.27%),but the difference was not statistically significant(χ2 = 2.91,P = 0.112).The quantitative score of dampness syndrome in the risk group was higher than that of the healthy group,and the difference was statistically significance(Z =-2.24,P = 0.025).(2)Among the study subjects at risk of cerebrovascular disease,evaluation time(χ2 = 26.11,P = 0.001),stroke risk grading(χ2= 8.85,P = 0.031),and history of stroke or transient ischemic attack(TIA)(χ2 = 9.28,P = 0.015)were the factors influencing the grading of dampness syndrome in the population at risk of cerebrovascular disease.Conclusion Dampness syndrome is the common TCM syndrome in the population of Guangdong area.The manifestations of dampness syndrome are more obvious in the population with risk factors of cerebrovascular disease,especially in the population at high risk of stroke,and in the population with a history of stroke or TIA.The assessment and intervention of dampness syndrome should be taken into account for future project of stroke prevention in Guangdong.
6.Hotspots and frontiers of human resource allocation research in public hospitals:a CiteSpace-based analysis of domestic and international studies
Ling YIN ; Tong ZHAO ; Jinping DI ; Fangjie WANG ; Haixiang SUN ; Qing ZHANG ; Xue ZHENG ; Wei CAO
Modern Hospital 2024;24(3):340-347,350
Objective To investigate the current status,evolving hotspots,and emerging trends in the field of human re-source allocation research in public hospitals,both domestically and internationally,to provide a reference for future research di-rections in China.Methods CiteSpace was used to conduct a visual analysis of the research literature on human resource alloca-tion in public hospitals based on China National Knowledge Infrastructure(CNKI)and the Web of Science(WOS).The analysis encompassed co-authorship,institutional collaboration,keyword co-occurrence and clustering,and burst detection.Results A total of 1 417 Chinese articles and 981 international articles were included.Domestic research in this field focused more on healthcare reform and management,resource allocation,hierarchical diagnosis,and treatment,and informatization and efficiency improvement.On the contrary,international research primarily centered on the employee satisfaction,healthcare system quality,work environment and medical staff.Future trends in domestic research included cost reduction,efficiency enhancement,and a greater emphasis on public welfare in public hospitals,while international research was beginning to explore the influence of polit-ical concepts in this field.Conclusion Compared to international research,domestic research needs to further improve its theo-retical and localized understanding,broaden its research scope,explore the interdisciplinary collaboration opportunities,and delve into research directions such as the application of artificial intelligence and automation technology in healthcare services,management of a diverse workforce,and innovative management techniques and applications.
7.Effect of Simo decoction on the regulation of NLRP3/Caspase-1/GSDMD signal pathway on duodenal microinflammation in rats with functional dyspepsia
Qin LIU ; Xiao-Yuan LIN ; Ling-Feng YANG ; Qian LUO ; Yun-Zong HAN ; Si-Qing CHEN ; Hai-Yue ZHANG ; Shu ZHOU ; Sai-Nan ZHOU
The Chinese Journal of Clinical Pharmacology 2024;40(1):67-71
Objective To investigate the effects of Simo decoction on duodenal microinflammation and NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)signaling pathway in rats with functional dyspepsia(FD).Methods The FD model was established by multifactorial method.SD rats were randomly divided into normal group,model group(FD model),positive control group(gavage administration of 0.305 mg·kg-1 mosapride injection)and experimental-H,-M,-L groups(gavage administration of 5.62,2.81,1.40 g·kg-1 Simo decoction).Small intestinal advancement rate and gastric emptying rate was determined;the levels of interleukin(IL)-1 β and IL-18 in serum were determined by enzyme linked immunosorbent assay(ELISA);the protein expression of NLRP3 and GSDMD in duodenal tissue was detected by Western blotting.Results The gastric emptying rates of normal,model,positive control and experimental-H,-M,-Lgroupswere(58.34±5.72)%,(29.16±8.37)%,(48.77±6.10)%,(48.35±6.04)%,(48.20±3.49)%and(39.24±4.20)%;the small intestinal propulsion rates were(82.01±7.55)%,(41.95±9.53)%,(64.61±10.18)%,(75.04±9.76)%,(60.58±7.13)%and(45.89±7.40)%;serum IL-1 β expression were(12.86±0.88),(43.73±4.60),(18.84±0.86),(24.61±1.57),(19.14±0.77)and(29.04±0.72)pg·mL-1;IL-18 expressions were(95.00±3.74),(170.60±8.78),(108.50±3.05),(118.90±3.45),(99.90±8.70)and(141.00±3.71)pg·mL-1;the relative expression levels of NLRP3 proteins were 0.32±0.02,0.84±0.05,0.42±0.03,0.48±0.02,0.61±0.04 and 0.62±0.05;the relative expression levels of GSDMD proteins were 0.34±0.05,0.93±0.06,0.35±0.03,0.52±0.02,0.53±0.06 and 0.55±0.05,respectively.Compared with the normal group,the above indexes in the model group have statistical significance;compared with the model group,the above indexes in the experimental-H group and the positive control group also have statistical significance(P<0.01 or P<0.05).Conclusion Simo decoction can effectively improve the general condition and duodenal microinflammation in FD rats,and the mechanism may be related to the inhibition of duodenal NLRP3/Caspase-1/GSDMD signaling pathway.
8.Evaluation of drug local tolerance testing and analysis of common problems
Mei-Ling CHEN ; Qing-Li WANG ; Hong-Mei GUANG ; Lan CUI ; Xiao-Dong ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(1):139-143
Conducting local tolerance testing on parentaral drugs is of great significance for evaluating the clinical medication risks of drugs.Although relevant domestic and international guidelines provide detailed instructions on how to conduct local tolerance testing,it was found that some products still provide non-standard application materials,which affects the efficiency of drug development.This article summarizes the information on domestic and international guidance related to the local tolerance testing and elaborates on common problems based on specific application cases,with the aim of of providing reference for related work.
9.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
10.Simultaneous determination of 6 aconitum-type alkaloids in Xiaozhong ointment by ultra-high performance liquid chromatography triple quadrupole mass spectrometry
Tian-Li XIA ; De-Ping ZHAO ; Ao XUE ; Mei-Ling JIN ; Zi-Yue ZHU ; Qing LI ; Ning ZHANG ; Xia LEI
The Chinese Journal of Clinical Pharmacology 2024;40(9):1341-1344
Objective To establish a method for the simultaneous determination of aconitine,neoaconitine,hypaconitine,benzoyl aconitine,benzoyl mesaconine and benzoylhypacoitine in Xiaozhong ointment by UPLC-TQD-MS.Methods ACQUITY UPLC BEH C18 column(50 mm ×2.1 mm,1.7 μm),mobile phase 0.1%formic acid water(A)-acetonitrile(B),gradient elution,column temperature 40 ℃,flow rate 0.3 mL·min-1,injection volume 5 μL;electrospray ionization source(ESI+)and multiple reaction monitoring(MRM)were used for mass spectrometry analysis.Results The concentration of aconitine,new aconitine,hypaconitine,benzoyl aconitine,benzoyl new aconitine and benzoyl hypaconitine were 1.0-100.0 ng·mL-1,respectively,the average recovery were 98.62%-101.24%.The mass fractions of the six components were 0.18,0.33,0.38,0.43,0.28,0.06μg·g-1.Conclusion The method can be used to determine the content of 6 aconitine-type alkaloids in Xiaozhong ointment,and provide reference for the quality evaluation and clinical safe use of Xiaozhong ointment.

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