1.Comparison of Wild and Cultivated Gardeniae Fructus Based on Traditional Quality Evaluation
Yuanjun SHANG ; Bo GENG ; Xin CHEN ; Qi WANG ; Guohua ZHENG ; Chun LI ; Zhilai ZHAN ; Junjie HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):225-234
ObjectiveBased on traditional quality evaluation of Gardeniae Fructus(GF) recorded in historical materia medica, this study systematically compared the quality differences between wild and cultivated GF from morphological characteristics, microscopic features, and contents of primary and secondary metabolites. MethodsVernier calipers and analytical balances were used to measure the length, diameter and individual fruit weight of wild and cultivated GF, and the aspect ratio was calculated. A colorimeter was used to determine the chromaticity value of wild and cultivated GF, and the paraffin sections of them were prepared by safranin-fast green staining and examined under an optical microscope to observe their microstructure. Subsequently, the contents of water-soluble and alcohol-soluble extracts of wild and cultivated GF were detected by hot immersion method under the general rule 2201 in volume Ⅳ of the 2020 edition of the Pharmacopoeia of the People's Republic of China, the starch content was measured by anthrone colorimetric method, the content of total polysaccharides was determined by phenol-sulfuric acid colorimetric method, the sucrose content was determined by high performance liquid chromatography coupled with evaporative light scattering detection(HPLC-ELSD), and the contents of representative components in them were measured by ultra-performance liquid chromatography(UPLC). Finally, correlation analysis was conducted between quality traits and phenotypic traits, combined with multivariate statistical analysis methods such as principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA), key differential components between wild and cultivated GF were screened. ResultsIn terms of traits, the wild GF fruits were smaller, exhibiting reddish yellow or brownish red hues with significant variation between batches. While the cultivated GF fruits are larger, displaying deeper orange-red or brownish red. The diameter and individual fruit weight of cultivated GF were significantly greater than those of wild GF, while the blue-yellow value(b*) of wild GF was significantly higher than that of cultivated GF. In the microstructure, the mesocarp of wild GF contained numerous scattered calcium oxalate cluster crystals, while the endocarp contained stone cell class round, polygonal or tangential prolongation, undeveloped seeds were visible within the fruit. In contrast, the mesocarp of cultivated GF contained few calcium oxalate cluster crystals, or some batches exhibited extremely numerous cluster crystals. The stone cells in the endocarp were predominantly round-like, with the innermost layer arranged in a grid pattern. Seeds were basically mature, and only a few immature seeds existed in some batches. Regarding primary metabolite content, wild GF exhibited significantly higher total polysaccharide level than cultivated GF(P<0.01). In category-specific component content, wild GF exhibited significantly higher levels of total flavonoids and total polyphenols compared to cultivated GF(P<0.01). Analysis of 12 secondary metabolites revealed that wild GF exhibited significantly higher levels of Shanzhiside, deacetyl asperulosidic acid methyl ester, gardenoside and chlorogenic acid compared to cultivated GF(P<0.01). Conversely, the contents of genipin 1-gentiobioside, geniposide and genipin were significantly lower in wild GF(P<0.01). ConclusionThere are significant differences between wild and cultivated GF in terms of traits, microstructure, and contents of primary and secondary metabolites. At present, the quality evaluation system of cultivated GF remains incomplete, and this study provides a reference for guiding the production of high-quality GF medicinal materials.
2.Targeting fibroblast growth factor receptor 1 signaling to improve bone destruction in rheumatoid arthritis
Haihui HAN ; Lei RAN ; Xiaohui MENG ; Pengfei XIN ; Zheng XIANG ; Yanqin BIAN ; Qi SHI ; Lianbo XIAO
Chinese Journal of Tissue Engineering Research 2025;29(9):1905-1912
BACKGROUND:Although researchers have noted that fibroblast growth factor receptor 1 shows great potential in rheumatoid arthritis bone destruction,there is a lack of reviews related to the potential mechanisms of fibroblast growth factor receptor 1 in rheumatoid arthritis bone destruction. OBJECTIVE:To comprehensively analyze the mechanism of fibroblast growth factor receptor 1 in bone destruction in rheumatoid arthritis by reviewing the relevant literature at both home and abroad. METHODS:We searched the CNKI database using the Chinese search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,bone cells,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,vascular endothelial cells."PubMed database was searched using the English search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,osteocytes,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,endothelial cells."The search period focused on April 1992 to January 2024.After screening the literature by reading titles,abstracts,and full texts,a total of 82 articles were finally included for review according to inclusion and exclusion criteria. RESULTS AND CONCLUSION:Fibroblast growth factor receptor 1 was found to be widely expressed in bone tissue-associated cells,including osteoblasts,osteoclasts,and osteoclasts.Fibroblast growth factor receptor 1 affects bone remodeling and homeostasis by regulating the function of these cells,as well as promoting the onset and progression of bone destruction in rheumatoid arthritis.Fibroblast growth factor receptor 1 is involved in the inflammatory response of synovial fibroblasts and macrophages and regulates angiogenesis of endothelial cells in synovial tissues.Fibroblast growth factor receptor 1 promotes bone destruction in several ways.Fibroblast growth factor receptor 1 may be a potential causative agent of bone destruction in rheumatoid arthritis and provides a reference for further research on its therapeutic targets.
3.Brief analysis on " Lijie and yellowish sweating" in Synopsis of Golden Chamber
Xin LAN ; Zilin REN ; Qi SHAO ; Yuxiao ZHENG ; Changxiang LI ; Fafeng CHENG ; Xueqian WANG ; Qingguo WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(2):161-165
" Lijie and yellowish sweating" originates from the chapter on stroke and arthralgia diseases in Synopsis of Golden Chamber. Later generations typically interpret it as yellow fluid oozing from painful joints, a characteristic manifestation of arthralgia. In Western medicine, Lijie corresponds to diseases such as gouty arthritis, with its primary clinical manifestations being redness, swelling, heat, and painful joints, most often without yellow fluid discharge. Therefore, the interpretation of " Lijie and yellowish sweating" contradicts the clinical manifestations often observed in this disease. Thus, this article reinterprets the meaning of " Lijie and yellowish sweating" from the pathogenesis of " sweat exposure to water, as if water harms the heart" , combined with the viewpoints of other medical practitioners. Determining the meaning of " yellowish sweating" is crucial for understanding the pathogenesis of arthralgia and clarifying the relationship between arthralgia and yellowish sweating. ZHANG Zhongjing mentioned arthralgia and " yellowish sweating" together, not to differentiate between the two diseases but to emphasize the common pathogenesis of the two, namely, the cold and dampness injuring the heart, blood, and vessels. This paper proposes a new explanation of " Lijie and yellowish sweating" , which suggests that " yellowish sweating" is not confined to the joints but can be found all over the body. The pathogenesis of " Lijie and yellowish sweating" lies in the insufficiency of the liver and kidney and exogenous water dampness, leading to disharmony between nutrient qi and defensive qi and between yin and yang. Primary treatment should harmonize yingfen and weifen, as well as tonify and replenish the liver and kidney. The clinical selection of medicines can be considered Guizhi Decotion, a type of formula. The pathogenesis of " Lijie and yellowish sweating" is complex, and clinical treatment should be comprehensively considered to achieve the best therapeutic effect.
4.Inhibition of HDAC3 Promotes Psoriasis Development in Mice Through Regulating Th17
Fan XU ; Xin-Rui ZHANG ; Yang-Chen XIA ; Wen-Ting LI ; Hao CHEN ; An-Qi QIN ; Ai-Hong ZHANG ; Yi-Ran ZHU ; Feng TIAN ; Quan-Hui ZHENG
Progress in Biochemistry and Biophysics 2025;52(4):1008-1017
ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4+ T lymphocytes, CD8+ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4+ T lymphocytes. Additionally, spleen CD4+ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4+ and CD8+ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4+ and CD8+ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4+ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4+ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.
5.Mechanisms of mitochondrial dynamics in ischemic stroke and therapeutic strategies.
Xin-Yue ZHENG ; Ming ZHANG ; Kai-Qi SU ; Zhi-Min DING
Acta Physiologica Sinica 2025;77(3):523-533
As a common neurological disease in China, stroke has an extremely high rate of death and disability, of which 80% is ischemic stroke (IS), causing a serious burden to individuals and society. Neuronal death is an important factor in the pathogenesis of stroke. Studies have shown that mitochondrial dynamics, as a key mechanism regulating intracellular energy metabolism and cell death, plays an important role in the pathogenesis of IS. In recent years, targeting mitochondrial dynamics has become an emerging therapeutic tool to improve neurological impairment after stroke. This paper reviews the research advance in recent years in IS mitochondrial dynamics, summarizing and discussing the overview of mitochondrial dynamics, the role of mitochondrial dynamics in IS, and the studies on mitochondrial dynamics-based treatment of IS. This paper helps to explore the mechanism of the role of mitochondrial dynamics in IS and effective interventions, and provides a theoretical strategy for targeting mitochondrial dynamics to treat IS in the clinic.
Humans
;
Mitochondrial Dynamics/physiology*
;
Ischemic Stroke/metabolism*
;
Mitochondria/physiology*
;
Animals
;
Brain Ischemia/physiopathology*
;
Energy Metabolism
6.Pharmacological effect and mechanism of tannic acids in Paeoniae Radix Alba.
Jia-Xin DIAO ; Qi-Tong ZHENG ; Meng-Yao CHEN ; Jiang-Chuan HONG ; Min HAO ; Qing-Mei FENG ; Jun-Qi HU ; Xia-Nan SANG ; Gang CAO
China Journal of Chinese Materia Medica 2025;50(6):1471-1483
The chemical composition of Paeoniae Radix Alba(PRA) is complex, with primary secondary metabolites including monoterpenoids, tannins, triterpenoids, and flavonoids. In previous studies on the material basis of PRA, it was found that, in addition to the widely studied characteristic monoterpene glycosides, tannic acid components also play an important role in the efficacy of PRA. However, their pharmacological effects have not been thoroughly investigated. This paper reviews the tannic acid components in PRA, including pentagaloyl glucose(PGG), tetragaloyl glucose(TGG), trigaloyl glucose(TriGG), and gallic acid, along with their structures, properties, and characteristics to provide a detailed discussion of their pharmacological activities and related mechanisms, aiming to offer a theoretical basis for the material basis research and clinical application of PRA.
Paeonia/chemistry*
;
Tannins/chemistry*
;
Humans
;
Drugs, Chinese Herbal/chemistry*
;
Animals
;
Plant Extracts
7.Biomechanical study and clinical application of two osteotomy guide methods in media open wedge high tibial osteotomy operation.
Chao QI ; Xiao-Ming LI ; Dong-Hui GUO ; Qiu-Ling SHI ; Yun-Chao ZHAO ; Jun DONG ; Zheng-Xin MENG ; Xing-Yue WANG
China Journal of Orthopaedics and Traumatology 2025;38(7):698-704
OBJECTIVE:
To explore the effectiveness and feasibility of two osteotomy guides in medial open wedge high tibial osteotomy (MOWHTO).
METHODS:
Clinical data of 103 patients who underwent routine MOWHTO surgery between January 2020 and December 2022 were collected for retrospective analysis. The patients were divided into two groups based on the method of osteotomy guide plate. The control group of 51 patients received traditional osteotomy guide plate technique, including 17 males and 34 females, aged from 48 to 68 years old with an average of(57.93±4.82) years old, with a disease duration ranged from 1 to 8 years with an average of (4.89±1.49) years. The observation group of 52 patients received personalized osteotomy guide plate technique, including 23 males and 29 females, aged from 48 to 69 with an average of (58.22±5.10) years, with a disease duration ranged from 1 to 9 years with an average of(5.10±1.55) years. The perioperative indicators, complications, and knee joint recovery rate were statistically analyzed for both groups, as well as the preoperative and postoperative coagulation function, fibrinogen (FIB), D-dimer (D-D), gait parameters (step frequency, step length, step speed), biomechanical indicators, weight bearing line (WBL), medial proximal tibial angle (MPTA), joint line conergence angle (JLCA), and anterior cruciate ligament (ACL) function (body width, tibial anterior displacement).
RESULTS:
All patients were followed up for 6 months. The intraoperative blood loss, operation time, and number of fluoroscopic views in the observation group were (358.58±93.76) ml, (84.42±8.17) min, and (2.00±0.44) times, respectively, which were all less than those in the control group (465.55±105.38) ml, (96.53±10.51) min, and (6.31±0.58) times (P<0.05). Three days after surgery, the FIB and D-D levels in the observation group were (4.21±0.48) g·L-1 and (204.47±35.59) μg·L-1, respectively, which were both lower than those in the control group (5.56±0.57) g·L-1 and (311.12±42.23) μg·L-1 (P<0.05). Three months after surgery, the step frequency, step length, and step speed in the observation group were (1.89±0.23) steps·s-1, (0.57±0.15) m, and (0.99±0.11) m·s-1, respectively, which were all higher than those in the control group (1.80±0.18) steps·s-1, (0.50±0.14) m, and (0.95±0.09) m·s-1 (P<0.05). Three months after surgery, the WBL and MPTA in the observation group were (45.53±4.41)% and (87.03±8.15)°, respectively, which were both higher than those in the control group (38.38±4.36)% and (83.68±8.50)°, and the JLCA was (2.36±0.24)°, which was lower than that in the control group (2.61±0.33)° (P<0.05). The ACL body width during internal fixation removal was (5.60±0.51) mm, which was greater than that in the control group (5.08±0.56) mm, and the tibial migration was (5.70±0.42) mm, which was less than that in the control group (6.33±0.48) mm (P<0.05). There was no significant difference in the incidence of complications between the two groups (P>0.05). Six months after surgery, there was no significant difference in the recovery rate of knee joint between the two groups (P>0.05).
CONCLUSION
The application of personalized osteotomy guide technique in MOWHTO can help improve knee biomechanics and ACL function, and has less effect on coagulation function and no increase in complications.
Humans
;
Male
;
Female
;
Osteotomy/methods*
;
Middle Aged
;
Tibia/physiopathology*
;
Aged
;
Biomechanical Phenomena
;
Retrospective Studies
;
Osteoarthritis, Knee/physiopathology*
8.Impact of sutureless dorsal venous complex combined with robotic-assisted laparoscopic prostatectomy on sexual function in patients with prostatic cancer.
Wei ZHENG ; Xin-Mian HUANG ; Xiao-Bo XU ; Ke-Bing YANG ; Xiao-Long QI ; Da-Hong ZHANG
National Journal of Andrology 2025;31(9):807-811
OBJECTIVE:
To evaluate the impact of sutureless approach to the dorsal venous complex (DVC) combined with robotic-assisted laparoscopic prostatectomy on sexual function of patients with prostatic cancer.
METHODS:
This study included 114 prostate cancer patients who underwent robot-assisted laparoscopic radical prostatectomy at our hospital from January 2021 to January 2024. The patients were randomly divided into a control group (n=57) and an observation group (n=57). The control group received conventional "figure-of-eight" suture ligation of the dorsal venous complex (DVC), while the observation group underwent direct DVC transection using monopolar electrocautery scissors after increasing pneumoperitoneum pressure.Surgical duration, intraoperative blood loss, positive surgical margin rates, and positive apical margin rates were recorded. The continence rates and rates of morning erections at 1, 3 and 6 months after the operation were compared between groups. Sexual function was assessed pre-operatively and at 6 months post-operation by using the IIEF-5 and PEDT.
RESULTS:
The operative time in the observation group was significantly longer than that in the control group ([115.71 ± 19.42] min vs [103.42 ± 12.78] min, P<0.05). While no significant differences were observed in intraoperative blood loss, positive surgical margin rate, or positive apical margin rate between the two groups (P>0.05). At 3 and 6 months after the operation, the observation group exhibited higher urinary continence rates and morning erection recovery rates compared to the control group (P<0.05). Furthermore, at 6 months postoperatively, the observation group demonstrated significantly higher IIEF-5 scores and lower PEDT scores than those of control group(P<0.05).
CONCLUSION
The use of a sutureless DVC technique in robotic-assisted laparoscopic radical prostatectomy protects the post-operative sexual function in patients.
Humans
;
Male
;
Prostatectomy/methods*
;
Laparoscopy/methods*
;
Prostatic Neoplasms/surgery*
;
Robotic Surgical Procedures/methods*
;
Middle Aged
;
Operative Time
;
Aged
9.A real-world study of first-line albumin-bound paclitaxel in the treatment of advanced pancreatic cancer in China
Juan DU ; Xin QIU ; Jiayao NI ; Qiaoli WANG ; Fan TONG ; Huizi SHA ; Yahui ZHU ; Liang QI ; Wei CAI ; Chao GAO ; Xiaowei WEI ; Minbin CHEN ; Zhuyin QIAN ; Maohuai CAI ; Min TAO ; Cailian WANG ; Guocan ZHENG ; Hua JIANG ; Anwei DAI ; Jun WU ; Minghong ZHAO ; Xiaoqin LI ; Bin LU ; Chunbin WANG ; Baorui LIU
Chinese Journal of Oncology 2024;46(11):1038-1048
Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P<0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.
10.A real-world study of first-line albumin-bound paclitaxel in the treatment of advanced pancreatic cancer in China
Juan DU ; Xin QIU ; Jiayao NI ; Qiaoli WANG ; Fan TONG ; Huizi SHA ; Yahui ZHU ; Liang QI ; Wei CAI ; Chao GAO ; Xiaowei WEI ; Minbin CHEN ; Zhuyin QIAN ; Maohuai CAI ; Min TAO ; Cailian WANG ; Guocan ZHENG ; Hua JIANG ; Anwei DAI ; Jun WU ; Minghong ZHAO ; Xiaoqin LI ; Bin LU ; Chunbin WANG ; Baorui LIU
Chinese Journal of Oncology 2024;46(11):1038-1048
Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P<0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.


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