1.Mechanism of Wumen Zhiqiao gancao decoction inhibiting pathological angiogenesis in degenerative intervertebral discs by regulating HIF-1α/VEGF/Ang signal axis
Zeling HUANG ; Zaishi ZHU ; Yuwei LI ; Bo XU ; Junming CHEN ; Baofei ZHANG ; Binjie LU ; Xuefeng CAI ; Hua CHEN
China Pharmacy 2025;36(7):807-814
OBJECTIVE To explore the effect and mechanism of Zhiqiao gancao decoction (ZQGCD) on pathological angiogenesis of degenerative intervertebral disc. METHODS The rats were randomly divided into sham operation group (normal saline), model group (normal saline), hypoxia inducible factor-1α (HIF-1α) inhibitor (YC-1) group [2 mg/(kg·d), tail vein injection], and ZQGCD low-dose, medium-dose and high-dose groups [3.06, 6.12, 12.24 g/(kg·d)], with 8 rats in each group. Except for sham operation group, lumbar disc degeneration model of rat was constructed in all other groups. After modeling, they were given relevant medicine once a day, for consecutive 3 weeks. After the last medication, pathological changes and angiogenesis of the intervertebral disc tissue in rats were observed; the levels of inflammatory factors [interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α)] and the expressions of angiogenesis-related proteins [HIF-1α, vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), angiotensin 1(Ang 1), Ang 2] in the com intervertebral disc tissue in rats were all determined. In cell experiment, the primary nucleus pulposus cells were isolated and cultured from rats, and cellular degeneration was induced using 50 ng/mL TNF-α. The cells were divided into blank control group (10% blank control serum), TNF-α group (10% blank control serum), YC-1 group (10% blank control serum+0.2 mmol/L YC-1), and 5%, 10%, 15% drug-containing serum group (5%, 10%, 15% drug-containing serum). After 24 hours of intervention, the nucleus pulposus cells were co-cultured with HUVEC. The expressions of Collagen Ⅱ, matrix metalloproteinase-3 (MMP-3) in nucleus pulposus cells were detected. HUVEC proliferation, migration and tube forming ability were detected, and the expression levels of the HIF-1α/VEGF/Ang signal axis and angiogenesis- related proteins (add MMP-2, MMP-9) in HUVEC were detected. RESULTS Animal experiments had shown that compared with model group, the positive expression of CD31 in the intervertebral disc tissues of rats in each drug group was down-regulated (P< 0.05), the levels of inflammatory factors and angiogenesis-related proteins were decreased significantly (P<0.05), and the pathological changes in the intervertebral disc were alleviated. Cell experiments had shown that compared with TNF-α group, the expression of Collagen Ⅱ in nucleus pulposus cells of all drug groups was significantly up-regulated (P<0.05), and the expression of MMP-3 was significantly down-regulated (P<0.05); the proliferation, migration and tubulogenesis of HUVEC were significantly weakened (P<0.05). The mRNA and protein expressions of HIF-1α, VEGF, Ang 2 as well as the expression of angiogenesis-related proteins (except for the expression of Ang 2 mRNA and HIF-1α, VEGFR2, Ang 2 protein in 5% drug- containing serum group) were significantly down-regulated (P<0.05). CONCLUSIONS ZQGCD may inhibit the HIF-1α/VEGF/ Ang signal axis to weaken the angiogenic ability of vascular endothelial cells, improve pathological angiogenesis in the intervertebral disc, and delay the degeneration of the intervertebral disc.
2.Timosaponin BⅡ Combined with Icariin Maintains Osteoclast-osteoblast Coupling by Restoring Yin-Yang Balance
Zaishi ZHU ; Zeling HUANG ; Weiye CAI ; Hua CHEN ; Boen SONG ; Yue LU ; Qing LU ; Xiaofeng SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):48-57
ObjectiveTo explore the effect of timosaponin BⅡ (TBⅡ) combined with icariin (ICA) on osteoclast (OC)-osteoblast (OB) coupling and decipher the mechanism from the cellular level. MethodsThe cell counting kit-8 (CCK-8) was used to assess the effects of different concentrations of TBⅡ and different concentrations of TBⅡ+ICA on the growth of RAW264.7 cells. Soluble receptor activator of nuclear factor-κB ligand (sRANKL) was used to induce the differentiation of RAW264.7 pre-osteoclasts into osteoclasts. The cells were allocated into sRANKL, TBⅡ (1, 5, 10 μmol·L-1), and TBⅡ+ICA groups. Tartrate-resistant acid phosphatase staining was performed to assess the effects of TBⅡ and TBⅡ+ICA on osteoclast differentiation. Real-time quantitative polymerase chain reaction (Real-time PCR) was conducted to examine the effects of TBⅡ+ICA on the expression of key genes involved in osteoclast differentiation and osteoclast-derived coupling factors. The osteogenic differentiation conditioned medium mixed with osteoclast supernatant was used to induce osteogenic differentiation of MC3T3-E1 cells. Alkaline phosphatase staining and alizarin red S staining were employed to determine the effect of TBⅡ+ICA on osteogenic differentiation. Real-time PCR was employed to evaluate the effects of conditioned medium on key genes involved in osteogenic differentiation. ResultsTBⅡ at 1, 5, 10 μmol·L-1 had no significant effect on the cell survival rate. Compared with the sRANKL group, TBⅡ inhibited osteoclast differentiation in a dose-dependent manner and achieved the best effect at 10 μmol·L-1 (P<0.01). Compared with the sRANKL group, different concentrations of TBⅡ down-regulated the mRNA levels of osteoclast differentiation-related genes c-Fos, RANK, and RANKL (P<0.05). None of 10 μmol·L-1 TBⅡ, 10 μmol·L-1 TBⅡ+10-4 μmol·L-1 ICA, or 10 μmol·L-1 TBⅡ+10-3 μmol·L-1 ICA affected the viability of RAW264.7 cells. TBⅡ and/or ICA inhibited osteoclast differentiation (P<0.01), and TBⅡ + ICA had the best effect (P<0.01). Compared with the sRANKL group, TBⅡ and/or ICA down-regulated the mRNA levels of c-Fos, RANK, and RANKL (P<0.05). The single application of TBⅡ and ICA had no significant effect on the mRNA levels of Wnt10b, Cthrc1, and C3a, while TBⅡ+ICA exerted up-regulating effects (P<0.05). Compared with those in the blank group, the bone differentiation and mineralization abilities of the normal osteogenic induction group and each osteogenic induction + osteoclast supernatant group were improved (P<0.01). Compared with the blank group, the normal osteogenic induction group and the osteogenic induction + osteoclast supernatant group showed up-regulated mRNA levels of Runx2 and OCN (P<0.01). ConclusionTBⅡ+ICA can inhibit osteoclast differentiation, maintain the normal osteoclast-osteoblast coupling, and promote osteogenic differentiation.
3.Deoxynivalenol contamination in cereals and bakery products in Shanghai and dietary exposure assessment in pregnant women
Kailin LI ; Baozhang LUO ; Renjie QI ; Hua CAI ; Xia SONG ; Jingjin YANG ; Danping QIU ; Zhenni ZHU ; Yi HE ; Hong LIU
Journal of Environmental and Occupational Medicine 2025;42(10):1170-1176
Background Deoxynivalenol (DON), a priority contaminant for food safety risk monitoring, is produced by Fusarium spp. infesting crops, and its common derivatives are 3-acetyl-DON (3A-DON) and 15-acetyl-DON (15A-DON), which have been shown to possess gastrointestinal toxicity, immunotoxicity, reproductive toxicity, and cytotoxicity. Due to the stable physicochemical properties of the DON family of toxins (DONs), they cannot be effectively removed during food processing, thus following the food chain, entering the human body, and posing health risks. Objective To understand the contamination status of DONs in commercial foods (cereals and bakery products) in Shanghai in 2022–2023, and to assess the exposure risk of DONs in pregnant women by combining their dietary consumption data. Methods Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to determine the contamination level of DONs in 1 100 food samples (cereals and baked goods) collected in 2022 and 944 samples collected in 2023 from Shanghai. The dietary monitoring data of pregnant women in Shanghai from 2016 to 2017 were adopted. The monitoring employed the food frequency questionnaire distributed among pregnant women through a combination of online telephone enquiry and offline on-site face-to-face survey to estimate their food consumption levels. An exposure assessment model was established to calculate the exposure level to DONs, and the probability distribution of the DONs exposure level in the pregnant women group in Shanghai was obtained by applying @Risk 7.5 software and simulating the calculation according to the Monte Carlo principle. With reference to the tolerable daily intake (TDI) of DONs [1.00 µg·(kg·d)−1] proposed by the Joint FAO/WHO Expert Committee on Food Additives, the risk of exposure to DONs from commercial cereals and bakery products in pregnant women in Shanghai was assessed. Results DONs were detected in cereal and bakery samples collected in 2022 and 2023 with different levels of contamination. The level of DONs in cereal foods in 2023 (mean: 36.33 µg·kg−1) decreased compared to 2022 (mean: 23.64 µg·kg−1). However, the positive rate (71.67%) and level (mean: 51.22 µg·kg−1) of DONs in bakery products increased significantly compared with 2022 (positive rate: 10.00%, mean: 24.39 µg·kg−1). The mean consumption of cereals in 783 pregnant women was 222.48 g·d−1 and the mean consumption of bakery products was 36.07 g·d−1, and there was no statistically significant difference in the intake of all types of cereals and bakery products across the early, middle, and late stages of pregnancy. The modelled intakes of DONs via commercial cereals and bakery products for pregnant women in Shanghai were calculated to be 0.20 and 0.57 µg·(kg·d)−1 in 2022 for the mean level and the 95th percentile level, respectively, and 0.16 µg·(kg·d)−1 and 0.35 µg·(kg·d)−1 in 2023, respectively. The results of the health risk assessment showed that pregnant women in Shanghai had 2.6% and 1.4% probability of exposure to DONs from cereal consumption in 2022 and 2023, respectively. Conclusion The risk of exposure of pregnant women in Shanghai to DONs via commercial cereals and bakery products is relatively low (1.4%-2.6%). However, considering the physical sensitivity of pregnant women, they should avoid consuming moldy grains and appropriately reduce intake of bakery products.
4.Effects of Rehmanniae Radix Praeparata on striatal neuronal apoptosis in ADHD rats via Bcl-2/Bax/caspase-3 pathway.
Jing WANG ; Kang-Lin ZHU ; Xin-Qiang NI ; Wen-Hua CAI ; Yu-Ting YANG ; Jia-Qi ZHANG ; Chong ZHOU ; Mei-Jun SHI
China Journal of Chinese Materia Medica 2025;50(3):750-757
This study investigated the effects of Rehmanniae Radix Praeparata on striatal neuronal apoptosis in rats with attention deficit hyperactivity disorder(ADHD) based on the B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X protein(Bax)/caspase-3 signaling pathway. Twenty-four 3-week-old male spontaneously hypertensive rats(SHR) were randomly divided into a model group, a methylphenidate group(2 mg·kg~(-1)·d~(-1)), and a Rehmanniae Radix Praeparata group(2.4 mg·kg~(-1)·d~(-1)). Age-matched male Wistar Kyoto(WKY) rats were used as the normal control group, with 8 rats in each group. The rats were administered by gavage for 28 days. Body weight and food intake were recorded for each group. The open field test and elevated plus maze test were used to assess hyperactivity and impulsive behaviors. Nissl staining was used to detect changes in striatal neurons and Nissl bodies. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) fluorescence staining was used to detect striatal cell apoptosis. Western blot was employed to detect the expression levels of Bcl-2, Bax, and caspase-3 proteins in the striatum. The results showed that compared with the model group, Rehmanniae Radix Praeparata significantly reduced the total movement distance, average movement speed, and central area residence time in the open field test, and significantly reduced the ratio of open arm entries, open arm stay time, and head dipping in the elevated plus maze test. Furthermore, it increased the number of Nissl bodies in striatal neurons, significantly downregulated the apoptosis index, significantly increased Bcl-2 protein expression and the Bcl-2/Bax ratio, and reduced Bax and caspase-3 protein expression. In conclusion, Rehmanniae Radix Praeparata can reduce hyperactivity and impulsive behaviors in ADHD rats. Its mechanism may be related to the regulation of the Bcl-2/Bax/caspase-3 signaling pathway in the striatum, enhancing the anti-apoptotic capacity of striatal neurons.
Animals
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Male
;
Apoptosis/drug effects*
;
Rats
;
Drugs, Chinese Herbal/administration & dosage*
;
Caspase 3/genetics*
;
Proto-Oncogene Proteins c-bcl-2/genetics*
;
bcl-2-Associated X Protein/genetics*
;
Rehmannia/chemistry*
;
Attention Deficit Disorder with Hyperactivity/physiopathology*
;
Signal Transduction/drug effects*
;
Neurons/cytology*
;
Rats, Inbred SHR
;
Rats, Inbred WKY
;
Humans
;
Corpus Striatum/cytology*
;
Plant Extracts
5.Buccal Acupuncture Alleviates Postoperative Pain in Patients Undergoing Radical Resection of Gastrointestinal Cancers: A Randomized Controlled Pilot Study.
Zhi-Xin ZHU ; Chen CHEN ; Yong-Feng ZHENG ; Wei-Li GONG ; Zheng CHEN ; Shi-Lei FANG ; Dong-Hua SHAO ; Cai-Xia SUN
Chinese journal of integrative medicine 2025;31(6):558-565
OBJECTIVE:
To preliminarily investigate the effect of buccal acupuncture therapy on ameliorating postoperative pain and enhancing recovery quality among patients undergoing radical resection of gastrointestinal cancers.
METHODS:
Fifty-two participants were randomized at a 1:1 ratio to either the buccal acupuncture or the control group. The acupuncture protocol entailed targeting 5 predetermined acupoints [CA-2 (Upper jiao), CA-3 (Middle jiao), CA-4 (Lower jiao), CA-6 (back), and CA-7 (waist) and two adjustable acupoints [CA-1 (head) and CA-8 (sacrum)] on each side of the face. The outcomes included the Numeric Rating Scale (NRS) scores for each day within 7 days postoperatively, 15-Item Quality of Recovery Scale (QoR-15) scores, analgesics consumption during and after surgery, incidences of postoperative nausea and vomiting, and perioperative levels of interleukin-6 and glucose. Adverse events related to acupuncture were recorded.
RESULTS:
Of the initial 52 participants, 46 completed the study and were included in the analysis. Findings indicated that the buccal acupuncture group experienced significantly reduced resting NRS scores in post-anesthesia care unit and throughout the postoperative phase (P=0.001 and P=0.003, respectively), along with enhanced QoR-15 scores on the 3rd postoperative day (P=0.008), compared to the control group. No notable differences were identified in the remaining indicators (P>0.05).
CONCLUSION
Buccal acupuncture therapy demonstrated significant effectiveness in reducing postoperative pain and improving recovery quality for patients undergoing radical resection of gastrointestinal cancers, presenting a viable intervention without associated adverse outcomes. (Trial registration No. ChiCTR2200060441).
Humans
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Male
;
Pilot Projects
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Female
;
Acupuncture Therapy/methods*
;
Pain, Postoperative/therapy*
;
Middle Aged
;
Gastrointestinal Neoplasms/surgery*
;
Aged
;
Acupuncture Points
;
Adult
6.Efficacy and safety of recombinant human anti-SARS-CoV-2 monoclonal antibody injection(F61 injection)in the treatment of patients with COVID-19 combined with renal damage:a randomized controlled exploratory clinical study
Ding-Hua CHEN ; Chao-Fan LI ; Yue NIU ; Li ZHANG ; Yong WANG ; Zhe FENG ; Han-Yu ZHU ; Jian-Hui ZHOU ; Zhe-Yi DONG ; Shu-Wei DUAN ; Hong WANG ; Meng-Jie HUANG ; Yuan-Da WANG ; Shuo-Yuan CONG ; Sai PAN ; Jing ZHOU ; Xue-Feng SUN ; Guang-Yan CAI ; Ping LI ; Xiang-Mei CHEN
Chinese Journal of Infection Control 2024;23(3):257-264
Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P<0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P>0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P>0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.
7.Risk assessment of cadmium exposure of Shanghai residents based on different dietary exposure assessment methods
Hua CAI ; Baozhang LUO ; Luxin QIN ; Danping QIU ; Jingjin YANG ; Xia SONG ; Biyao XU ; Zhenni ZHU ; Hong LIU ; Chunfeng WU
Shanghai Journal of Preventive Medicine 2024;36(3):224-229
ObjectiveTo conduct comprehensive assessment of internal and external cadmium exposure and health risks for Shanghai residents. MethodsCadmium levels in food samples were calculated by employing two dietary exposure assessment methods, total diet study (TDS) and food frequency questionnaire (FFQ), to estimate the daily dietary cadmium exposure of Shanghai residents. The provisional tolerable monthly intake (PTMI) of cadmium set by joint food and agriculture organization/WHO expert committee on food additives (JECFA) was applied to evaluate the health risk. Differences in dietary and urinary cadmium were compared by rank-sum test among different regions, age, gender, smoking status, and BMI groups, and the association between internal and external cadmium exposure was investigated by correlation analysis. ResultsThe mean value of urinary cadmium for 1 300 respondents was 0.542 μg·L-1. Urinary cadmium was higher in the population in central urban and urban-rural fringe areas than in the suburban area, higher in the older age group than in the younger age group, and higher in the smoking group than in the non-smoking group (all P<0.01). The two assessment methods showed that the mean values of daily dietary cadmium exposure for Shanghai residents were 0.306 and 0.090 μg·kg-1, with 3.69% and 0.85% of Shanghai residents exceeding the PTMI, respectively. Correlation analyses showed that dietary exposure to cadmium based on the FFQ method was positively correlated with the urinary cadmium level when smoking status, age, gender, and BMI were adjusted. ConclusionDietary exposure to cadmium of Shanghai residents is mainly derived from vegetables, aquatic products, cereals and potatoes, and is overall at a low-risk level. Dietary exposure assessment based on FFQ and risk monitoring data can effectively estimate long-term cadmium exposure.
8.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.
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.Treatment of Neer Ⅱ b distal clavicular fracture with locking plate under arthroscope
Shao CHEN ; Cai-Hua ZHANG ; Quan-Ming YANG ; Xin-Chun LI ; Ying-Chun ZHU
China Journal of Orthopaedics and Traumatology 2024;37(10):1010-1014
Objective To investigate the feasibility and clinical effect of the treatment of Neer Ⅱ b distal clavicular fracture with locking plate under arthroscopy.Methods Between June 2018 and September 2022,the medical records of 15 patients with Neer Ⅱ b distal clavicular fracture treated with locking plate under arthroscope were retrospectively analyzed,including 9 males and 6 females,aged from 25 to 57 years old with an average of(42.50±7.75)years old,5 left shoulder,10 right shoul-der,and duration of the disease ranged from 4 to 7 days with an average of(5.16±0.98)d.Visual analog score(VAS),Con-stant-Murley shoulder joint score scale and Neer standard score were used before operation,1 month after operation and the last follow-up.Results All patients successfully completed the treatment of Neer Ⅱ b distal clavicular fracture with locking plate under arthroscopy,with the operation time ranging from 0.3 to 1.0 h with an average of(0.55±0.24)h.All patients were healed at stage Ⅰ.The follow-up time ranged from 6 to 15 months with an average of(9.2±2.8)months.The preoperative VAS score was 7.23±0.67,the Constant-Murley shoulder joint score was(19.57±0.91),and the Neer standard score was(11.27±1.12);The VAS score was(1.56±0.81),the Constant-Murley shoulder joint score was(52.62±1.54),and the Neer standard score was(61.98±2.99)in the first month after operation;At the last follow-up,the VAS was(0.42±0.54),the Constant-Murley shoulder joint score was(91.24±1.97),and the Neer standard score was(93.24±3.38).The difference between VAS,Con-stant-Murley shoulder joint score and Neer standard score was statistically significant at one month postoperative and preoper-ative(P<0.05),and the difference between the last follow-up visit and one month postoperative was statistically significant(P<0.05).Conclusion The treatment of Neer Ⅱ b distal clavicular fracture with locking plate under arthroscope can restore the function of shoulder joint,with definite curative effect and feasibility.

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