1.Therapeutic effect of anti-PD-L1&CXCR4 bispecific nanobody combined with gemcitabine in synergy with PBMC on pancreatic cancer treatment
Hai HU ; Shu-yi XU ; Yue-jiang ZHENG ; Jian-wei ZHU ; Ming-yuan WU
Acta Pharmaceutica Sinica 2025;60(2):388-396
Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8+ to CD4+ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8+ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).
2.Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0
Di WU ; Jia-Horng KAO ; Teerha PIRATVISUTH ; Xiaojing WANG ; Patrick T.F. KENNEDY ; Motoyuki OTSUKA ; Sang Hoon AHN ; Yasuhito TANAKA ; Guiqiang WANG ; Zhenghong YUAN ; Wenhui LI ; Young-Suk LIM ; Junqi NIU ; Fengmin LU ; Wenhong ZHANG ; Zhiliang GAO ; Apichat KAEWDECH ; Meifang HAN ; Weiming YAN ; Hong REN ; Peng HU ; Sainan SHU ; Paul Yien KWO ; Fu-sheng WANG ; Man-Fung YUEN ; Qin NING
Clinical and Molecular Hepatology 2025;31(Suppl):S134-S164
As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.
3.Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0
Di WU ; Jia-Horng KAO ; Teerha PIRATVISUTH ; Xiaojing WANG ; Patrick T.F. KENNEDY ; Motoyuki OTSUKA ; Sang Hoon AHN ; Yasuhito TANAKA ; Guiqiang WANG ; Zhenghong YUAN ; Wenhui LI ; Young-Suk LIM ; Junqi NIU ; Fengmin LU ; Wenhong ZHANG ; Zhiliang GAO ; Apichat KAEWDECH ; Meifang HAN ; Weiming YAN ; Hong REN ; Peng HU ; Sainan SHU ; Paul Yien KWO ; Fu-sheng WANG ; Man-Fung YUEN ; Qin NING
Clinical and Molecular Hepatology 2025;31(Suppl):S134-S164
As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.
4.Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0
Di WU ; Jia-Horng KAO ; Teerha PIRATVISUTH ; Xiaojing WANG ; Patrick T.F. KENNEDY ; Motoyuki OTSUKA ; Sang Hoon AHN ; Yasuhito TANAKA ; Guiqiang WANG ; Zhenghong YUAN ; Wenhui LI ; Young-Suk LIM ; Junqi NIU ; Fengmin LU ; Wenhong ZHANG ; Zhiliang GAO ; Apichat KAEWDECH ; Meifang HAN ; Weiming YAN ; Hong REN ; Peng HU ; Sainan SHU ; Paul Yien KWO ; Fu-sheng WANG ; Man-Fung YUEN ; Qin NING
Clinical and Molecular Hepatology 2025;31(Suppl):S134-S164
As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.
5.The Application of Spatial Resolved Metabolomics in Neurodegenerative Diseases
Lu-Tao XU ; Qian LI ; Shu-Lei HAN ; Huan CHEN ; Hong-Wei HOU ; Qing-Yuan HU
Progress in Biochemistry and Biophysics 2025;52(9):2346-2359
The pathogenesis of neurodegenerative diseases (NDDs) is fundamentally linked to complex and profound alterations in metabolic networks within the brain, which exhibit marked spatial heterogeneity. While conventional bulk metabolomics is powerful for detecting global metabolic shifts, it inherently lacks spatial resolution. This methodological limitation hampers the ability to interrogate critical metabolic dysregulation within discrete anatomical brain regions and specific cellular microenvironments, thereby constraining a deeper understanding of the core pathological mechanisms that initiate and drive NDDs. To address this critical gap, spatial metabolomics, with mass spectrometry imaging (MSI) at its core, has emerged as a transformative approach. It uniquely overcomes the limitations of bulk methods by enabling high-resolution, simultaneous detection and precise localization of hundreds to thousands of endogenous molecules—including primary metabolites, complex lipids, neurotransmitters, neuropeptides, and essential metal ions—directly in situ from tissue sections. This powerful capability offers an unprecedented spatial perspective for investigating the intricate and heterogeneous chemical landscape of NDD pathology, opening new avenues for discovery. Accordingly, this review provides a comprehensive overview of the field, beginning with a discussion of the technical features, optimal application scenarios, and current limitations of major MSI platforms. These include the widely adopted matrix-assisted laser desorption/ionization (MALDI)-MSI, the ultra-high-resolution technique of secondary ion mass spectrometry (SIMS)-MSI, and the ambient ionization method of desorption electrospray ionization (DESI)-MSI, along with other emerging technologies. We then highlight the pivotal applications of spatial metabolomics in NDD research, particularly its role in elucidating the profound chemical heterogeneity within distinct pathological microenvironments. These applications include mapping unique molecular signatures around amyloid β‑protein (Aβ) plaques, uncovering the metabolic consequences of neurofibrillary tangles composed of hyperphosphorylated tau protein, and characterizing the lipid and metabolite composition of Lewy bodies. Moreover, we examine how spatial metabolomics contributes to constructing detailed metabolic vulnerability maps across the brain, shedding light on the biochemical factors that render certain neuronal populations and anatomical regions selectively susceptible to degeneration while others remain resilient. Looking beyond current applications, we explore the immense potential of integrating spatial metabolomics with other advanced research methodologies. This includes its combination with three-dimensional brain organoid models to recapitulate disease-relevant metabolic processes, its linkage with multi-organ axis studies to investigate how systemic metabolic health influences neurodegeneration, and its convergence with single-cell and subcellular analyses to achieve unprecedented molecular resolution. In conclusion, this review not only summarizes the current state and critical role of spatial metabolomics in NDD research but also offers a forward-looking perspective on its transformative potential. We envision its continued impact in advancing our fundamental understanding of NDDs and accelerating translation into clinical practice—from the discovery of novel biomarkers for early diagnosis to the development of high-throughput drug screening platforms and the realization of precision medicine for individuals affected by these devastating disorders.
6.Impact of rigid container material type and loading volume on the sterilization of thoracoscopic instruments
Xue'e FANG ; Yanjun MAO ; Qiuping ZHU ; Yanni CAI ; Jing SHU ; Guifen ZHANG ; Yichun JIN ; Minye TANG ; Ying TAO ; Huiting HU
Shanghai Journal of Preventive Medicine 2025;37(8):697-699
ObjectiveTo explore the impacts of material type and loading volume of rigid containers on the hydrogen peroxide low temperature plasma sterilization of thoracoscopic instruments, to identify the best rigid containers and loading volume of thoracoscopic instruments. MethodsThoracoscopic instruments sterilized by STERRAD® 100NX hydrogen peroxide low temperature plasma in Shanghai Pulmonary Hospital affiliated to Tongji University from August to September 2024 were selected as the research items. According to the material of rigid containers, the instruments were divided into polyethylene case group (A), stainless steel case group (B) and silicone resin case group (C). In terms of the loading volume, the rigid containers were divided into (loading capacity <80%) groups of 8, 10 and 12 instruments. The results of physical monitoring, the first type of chemical indicator card monitoring, and the five types of card luminal chemical process challenge device (PCD) monitoring of the 9 groups of A8, A10, A12, B8, B10, B12, C8, C10 and C12 were compared and evaluated. ResultsCompared to A8, A10 A12, C8, C10 or C12 groups, the thoracoscope instruments in the stainless steel containers in B8, B10 or B12 group had higher hydrogen peroxide concentrations and shorter elapsed time in the pressure check phases 1 and phases 2, with the differences statistically significant (P<0.05), followed by the silicone resin case group and the polyethylene case group. The nine groups of physical parameter monitoring, the first type of chemical indicator monitoring, and the five types of chemical PCD monitoring for lumen sterilization achieved 100% qualification rates, and there were no significant differences in the qualified rates of sterilization among the 9 groups (P>0.05). ConclusionWhen using hydrogen peroxide low temperature plasma to sterilize thoracoscopic instruments, it is recommended to use stainless steel or silicone resin rigid containers with a controlled loading capacity (≤12) to ensure optimal sterilization quality.
7.Exploring the idea of differentiating and treating mild cognitive impairment due to Alzheimer′s disease based on latent toxin blocking collaterals
Hu XI ; Wenming YANG ; Hao LI ; Wenting XIE ; Yue YANG ; Shu ZHAI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):559-565
Mild cognitive impairment due to Alzheimer′s disease is an inevitable pathological stage in the early development of Alzheimer′s disease, which can be classified as "microlumps in the brain collaterals" in traditional Chinese medicine. Based on the theory of latent toxin blocking collaterals, this article discusses the etiology and pathogenesis, clinical sequelae, and traditional Chinese medicine intervention strategies for mild cognitive impairment due to Alzheimer′s disease. The onset of mild cognitive impairment due to Alzheimer′s disease is very similar to the latent pathogen theory, which states that "the latent pathogen is latent and then develops, the poison is deep and difficult to cure, and the development can be recognized but the latent pathogen cannot be detected." Combining clinical experience, our team believes that the basic nature of the disease is a slight deficiency and a slight excess of symptoms. A slight deficiency of the five zang viscera and six fu viscera as root and a latent toxin colling collaterals of qi, fire, phlegm, and blood stasis as manifestaion. These usually start from the qi depression and develop into phlegm coagulation and blood stasis, then end up in latent toxin and gradually become the healthy qi deficiency. Therefore, the deficiency of vital qi and incubation of evil, latent toxin blocking collaterals the pathogenesis of early intervention of this disease should be carried out, upholding the idea that "the upper workman treats the disease before it is diagnosed." The principle of strengthening vital qi to eliminate pathogenic factors, slowing down and promoting pathogenic factors elimination, establishing the method of supporting correctness and wisdom, simultaneously detoxifying and clearing the blood stasis, pattern differentiation as the main and the disease differentiation as the first, combining the disease and pattern, and adjusting the macroscopic and microscopic, focusing simultaneously on eliminating and replenishing, dispel phlegm and remove blood stasis, achieve a strong vital qi and the elimination of evil, and enhance intelligence, delay or even block the progression of mild cognitive impairment due to Alzheimer′s disease, improve patients′ quality of life, and provide a theoretical basis for the early clinical prevention and treatment of Alzheimer′s disease.
8.Sex differences in cardiovascular health among children aged 6-8 years in Beijing City
GUAN Mengying, JIANG Xiaofeng, SHU Wen, LI Menglong, XIAO Huidi, ASIHAER Yeerlin, HU Yifei
Chinese Journal of School Health 2024;45(1):36-40
Objective:
To explore sex difference in the cardiovascular health (CVH) status of 6-8 year old children in Beijing, so as to inform the early intervention of CVH related lifestyles.
Methods:
Based on the Beijing Children s Growth and Health Cohort (PROC), baseline physical examination, sequential questionnaire survey, and laboratory tests were conducted among 1 914 grade 1 students. Children s CVH and its subscales (health behaviors and health factors) scores were calculated according to the Life s Essential 8 (LE 8) index and categorized into high, moderate, and low CVH. CVH scores were reported as medians and interquartile ranges; sex differences were compared using the Chi square test and Wilcoxon test.
Results:
Among the 1 914 participants, the percentages of high, moderate, and low CVH were 35.7%, 63.5%, and 0.8%, respectively, and the percentages of high, moderate, and low health behavior scores were 25.9%, 67.5%, and 6.6%, respectively, with no statistically significant differences between sex ( χ 2=2.30, 0.07, P >0.05). The rates of high, moderate, and low health factor scores for boys and girls were 61.1%, 36.0%, 2.9% and 71.1%, 28.4%, 0.5%, respectively, with a statistically significant sex difference ( χ 2=31.88, P < 0.01). The overall CVH score was 76.0(70.0, 83.0), 76.0(69.0, 82.0) for boys, and 77.0(71.0, 83.0) for girls. Among the health behavior metrics, sleep scores were the best and physical activity scores were the worst[100.0(90.0,100.0), 40.0(20.0, 80.0 )]; among the health factor metrics, blood glucose scores were the best and lipid scores were the worst[100.0(100.0,100.0), 60.0(40.0,100.0)]. In respect to health factors, there were significant gender differences in body mass index, blood lipids, blood sugar, and blood pressure scores ( Z =-6.92, 3.01, -6.60, -2.30, <0.05), but there were no significant gender differences in diet, physical activity, nicotine exposure, or sleep scores with regards to health behaviors ( Z =0.99, 0.88, -0.13, 0.36, P > 0.05 ). Compared to boys, girls in the low and moderate CVH groups had high health factor scores despite low health behavior scores.
Conclusion
Most 6 to 8-year-old children in Beijing were found to have relatively good CVH, and optimization of children s CVH status can be achieved by promoting healthier lifestyles and monitoring health factors, especially among boys.
9.Study on the effect of different administration regimens of iprrazole enteric-coated tablets on inhibiting gastric acid secretion
Ting-Yuan PANG ; Zhi WANG ; Zi-Shu HU ; Zi-Han SHEN ; Yue-Qi WANG ; Ya-Qian CHEN ; Xue-Bing QIAN ; Jin-Ying LIANG ; Liang-Ying YI ; Jun-Long LI ; Zhi-Hui HAN ; Guo-Ping ZHONG ; Guo-Hua CHENG ; Hai-Tang HU
The Chinese Journal of Clinical Pharmacology 2024;40(1):92-96
Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH>3 after 20 mg qd and 10 mg bid were 82.64%and 61.92%,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.
10.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.


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