1.Association Between MTHFR C677T Gene Polymorphism and Hypertension, Hyperhomocysteinemia and Hyperlipidemia in Tibet Region
Pengchang LI ; Danni MU ; Zhijuan LIU ; Xiaoxing LIU ; Puchi ZEJI ; Liping TIAN ; Honglei LI ; Li'an HOU ; Dandan LI ; Jie WU ; Ling QIU
Medical Journal of Peking Union Medical College Hospital 2026;17(1):280-285
To explore the correlation between MTHFR C677T gene polymorphism and hypertension, hyperhomocysteinemia(Hcy), and hyperlipidemia in the Tibetan population of Tibet. Using a cluster sampling method, participants from high-altitude regions including Ngari Prefecture, Lhasa City, and Nyingchi City in Tibet were enrolled. Differences in MTHFR C677T genotype distribution among individuals with hypertension, HHcy, and hyperlipidemia were analyzed, and multivariate logistic regression was performed to assess the association between these conditions and the TT genotype. A total of 574 eligible subjects were included, with a mean age of 40.64±12.67 years. Males accounted for 46.7%(268/574) and females 53.3%(306/574). Regional distribution was 34.8%(200/574) from Nyingchi City, 33.1%(190/574) from Lhasa City, and 32.1%(184/574) from Ngari Prefecture. Mean systolic and diastolic blood pressures were 117.89±18.98 mm Hg and 79.74±14.88 mm Hg, respectively. The frequency of the TT genotype was significantly higher in the hypertension group than in the non-hypertension group(12.32% The MTHFR C677T TT genotype is significantly associated with hypertension and hyperhomocysteinemia in the Tibetan population, suggesting that this polymorphism may be a genetic risk factor for these diseases in high-altitude regions.
2.Effects of di(2-ethylhexyl) phthalate on glucose homeostasis in rats due to impaired autophagy flux of islet β cells mediated by oxidative stress
Hongyang ZHOU ; Yuting HU ; Xue CHEN ; Yunqiang ZHOU ; Liping LI ; Ling LI ; Herong LIU
Journal of Environmental and Occupational Medicine 2025;42(6):674-683
Background Di(2-ethylhexyl) phthalate (DEHP) is the most prevalent environmental endocrine disruptor among phthalate acid esters (PAEs) worldwide. Previous studies have indicated that exposure to DEHP may disrupt glucose metabolism. Objective To investigate the impact of DEHP on glucose homeostasis in rats, focusing on oxidative stress-induced impairment of autophagy in islet β cells. Methods Forty male SD rats were randomly assigned to four groups, receiving DEHP doses of 0, 187, 375, and 750 mg·kg−1 for 12 weeks. Oral glucose tolerance (OGTT) and insulin tolerance tests (ITT) were conducted 24 h after the final exposure. Pancreatic microstructural alterations were assessed using hematoxylin and eosin (HE) staining and transmission electron microscopy (TEM). Commercial ELISA kits were employed to quantify the levels of insulin, adenosine triphosphate (ATP), and adenosine monophosphate (AMP) in rat serum, as well as the protein expression level of activated caspase-3 in pancreatic tissue. Additionally, commercial microplate kits were utilized to measure the concentration of reduced glutathione (GSH) in serum, the activity of superoxide dismutase (SOD) using water-soluble tetrazolium salt-1, the content of malondialdehyde (MDA) by thiobarbituric acid method, and the level of reactive oxygen species (ROS) in pancreatic tissue by chemical fluorescence method. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure sequestosome1 (SQSTM1/p62), Beclin1, microtubule-associated protein 1 light chain 3 (LC3), and cysteinyl aspartate specific proteinase-8 (Caspase-8) mRNA levels. Western blot analysis was applied to detect the protein relative expression levels of p62, Beclin-1, LC3-I, LC3 II, AMPK, p-AMPK, mTOR, p-mTOR, ULK1, and Caspase-8. Results Compared to the 0 mg·kg−1 DEHP group, the 750 mg·kg−1 DEHP group exhibited a significant increase in fasting blood glucose levels at 2, 4, 6, and 12 weeks (P<0.05). The OGTT showed that, following high-glucose gavage, the 187 mg·kg−1 DEHP group had elevated blood glucose at 30 min (P<0.05), the 375 mg·kg−1 DEHP group showed increased glucose levels at 15, 30, and 180 min (P<0.05), and the 750 mg·kg−1 DEHP group exhibited elevated levels at 15, 30, 60, and 180 min (P<0.05). The 375 and 750 mg·kg−1 DEHP groups demonstrated significantly increased OGTT area under the curve (AUC) values (P<0.05). In contrast, ITT results indicated no significant differences in blood glucose levels or AUC among the DEHP exposure groups at all time points (P>0.05). Compared to the 0 mg·kg−1 DEHP group, the 750 mg·kg−1 DEHP group exhibited significantly higher HOMA-IR levels and markedly lower HOMA-ISI values (P<0.05). HE and TEM showed that in each DEHP exposure group, the number of islet cells decreased, the islet area reduced, and chromatin condensation occurred. The endocrine granules in the cytoplasm of islet β cells decreased, and there were varying degrees of widening of the nuclear membrane gap, flattening and expansion of the Golgi complex, and expansion of the endoplasmic reticulum. Ribosome separation was observed, and autophagosomes were visible. In the 375 and 750 mg·kg−1 DEHP groups, the mitochondria were deformed to varying degrees, and some cristae structures disappeared, presenting vacuolization. Moreover, the chromatin condensation in the nuclei was more severe in the 750 mg·kg−1 DEHP group. The serum SOD activity was significantly elevated in the 750 mg·kg−1 DEHP group (P<0.05). Both the 375 mg·kg−1 and 750 mg·kg−1 DEHP groups exhibited a significant increase in the relative ROS content in pancreatic tissue (P<0.05). In DEHP-treated groups, the MDA content increased (P<0.05), while the GSH content decreased (P<0.05). Additionally, in the 750 mg·kg−1 DEHP group, the AMP/ATP ratio in serum was significantly raised (P<0.05), and the expression of cleaved Caspase-3 protein in pancreatic tissue was also significantly increased (P<0.05). The relative mRNA levels of p62, Beclin-1, LC3, and Caspase-8 in the pancreatic tissue of rats exposed to DEHP were significantly elevated (P<0.05). The relative expression levels of p-AMPK/AMPK, p-ULK1/ULK1, and Beclin-1 proteins in the DEHP-treated groups were significantly increased (P<0.05). In the 375 mg·kg−1 and 750 mg·kg−1 DEHP treatment groups, the relative expression levels of p62, LC3 II/LC1, and Caspase-8 proteins were significantly increased (P<0.05), while the relative expression level of p-mTOR/mTOR was significantly decreased (P<0.05). Conclusion DEHP can disrupt glucose homeostasis by inducing oxidative stress, which subsequently activates autophagy via the ROS/AMPK/ULK1 pathway, impairing autophagic flux and promoting apoptosis of islet β cells, ultimately decreasing their function and number.
3.Differential Analysis on Chemical Composition and Pharmacodynamic Effect Between Combined Decoction and Single Decoction of Famous Classical Formula Huaganjian
Yang WANG ; Gaoju ZHANG ; Ling LI ; Liping CHEN ; Li ZHANG ; Xiao LIU ; Yuyu ZHANG ; Yuan CUI ; Minglong LI ; Chaomei FU ; Xin YAN ; Yuxin HE ; Qin DONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):199-207
ObjectiveThrough qualitatively and quantitatively analysis of the differences in chemical composition between the combined decoction and single decoction of Huaganjian and comparison of their core efficacy, to explore the rationality of the flexible clinical application of Huaganjian compound preparations and single-flavored dispensing granules. MethodsUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was used to qualitatively analyze the combined decoction and single decoction samples of Huaganjian, and meanwhile, the contents of four index components(geniposide, paeoniflorin, hesperidin and paeonol) were quantitatively analyzed by high performance liquid chromatography(HPLC). Nonalcoholic fatty liver disease(NAFLD) rat model induced by high-fat diet was applied to compare the efficacy of combined decoction and single decoction of Huaganjian. A total of 30 male SD rats were randomly divided into the control group, model group, lovastatin group(1.8 mg·kg-1), combined decoction group(1.26 g·kg-1) and single decoction group(1.18 g·kg-1). After successful modeling, lovastatin group, combined decoction group and single decoction group were given corresponding doses of drugs by intragastric administration every day, and the control group and model group were given equal amounts of normal saline by intragastric administration, after 4 weeks of administration, the serum and liver tissues were collected, and the contents of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) in serum of rats were detected, and the liver pathological examination was carried out by hematoxylin-eosin(HE) staining and oil red O staining, so as to compare differences of their efficacy. ResultsSeventy chemical components were initially identified and attributed from the lyophilized powder of the combined decoction and single decoction samples of Huaganjian, and there was no obvious difference in composition between the two. Further quantitative analysis showed that the contents of geniposide, paeoniflorin, hesperidin and paeonol in the combined decoction samples were significantly increased when compared with those of the single decoction samples(P<0.01). The pharmacodynamic results showed that compared with the model group, both the combined and single decoction groups of Huaganjian could improve the liver index of NAFLD rats, reduce the serum levels of AST, ALT, TC, TG and LDL-C, increase the serum level of HDL-C, and ameliorate the pathological changes of liver cell steatosis and fat accumulation. However, there was no significant difference in pharmacodynamic effects between the combined decoction group and the single decoction group. ConclusionThere is no significant difference between the combined decoction and single decoction of Huaganjian in terms of chemical composition, but the contents of the four index components show significantly difference. Both of them can significantly improve the fat accumulation and liver function in NAFLD rats. This study provides a reference basis for the rational clinical application and evaluation of famous classical formula compound preparations and single-flavored dispensing granules.
4.Herbal Textual Research on Cnidii Fructus in Famous Classical Formulas
Huifang HU ; Liping YANG ; Fei CHEN ; Xiaohui MA ; Ling JIN ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):243-253
In this paper, by referring to ancient and modern literature, the textual research of Cnidii Fructus has been conducted to clarify the name, origin, distribution of production areas, quality specification, nature and flavour, efficacy, harvesting and processing, compatibility taboo and others, so as to provide reference and basis for the development and utilization of the relevant famous classical formulas. After textual research, it can be verified that Cnidii Fructus was first published in Sheng Nong's Herbal Classic, the materia medica of all dynasties was named Shechuangzi, and there are also aliases such as Shesu, Shemi, and Qiangmi. The main source for generations was the dried ripe fruit of Cnidium monnieri, and ancient and modern consistent. From the Eastern Han dynasty to Tang dynasty, the origin of Cnidii Fructus was Zibo, Shandong province. During the Five dynasties, it expanded to Yangzhou in Jiangsu province and Xiangyang in Hubei province, the Song dynasty added Shangqiu in Henan province, and it was considered that Yangzhou, Xiangyang and Shangqiu were its genuine producing areas. It was more widely distributed in Ming and Qing dynasties. After the founding of the People's Republic of China, the origin is clearly distributed throughout the country. For its quality evaluation, generally full grain, gray yellow color, strong aroma is the best. The harvesting period in the past dynasties was mostly the fifth lunar month, and the fruit was collected to remove impurities and dry. The mainstream processing in producing area of the past dynasties was net selection of raw products, mixing and steaming with the juice of Rehmanniae Radix and stir-frying were the mainstream processing methods in the past, there were also stir-frying with honey, stir-frying with salt and rice wine, immersing and steaming with rice wine and other methods. In recent times, it has been used in raw products as medicine. Sheng Nong's Herbal Classic recorded Cnidii Fructus was bitter, Supplementary Records of Famous Physicians recorded its acrid for the first time. It was recorded in the Ming dynasty that its nature was warm, acted on the kidney meridian, and had small toxicity. After the founding of the People's Republic of China, most of the literature classified it as a medicine to attack poison, kill insects and relieve itching with the functions of dispelling pathogenic wind and removing dampness, destroying parasites and elieving itching, warming kidney and activating Yang. Clinical contraindications are mainly contraindicated for people with damp-heat from the lower-jiao or kidney heat. Based on the textual research, it is suggested that when developing the famous classical formulas containing Cnidii Fructus, the source shall be the dried ripe fruit of C. monnieri, and then it shall be processed according to the original formulas. If there is no requirement for processing in the formulas, the raw products can be taken into medicine.
5.Herbal Textual Research on Moschus in Famous Classical Formulas
Juanjuan LIU ; Sini LI ; Jie JI ; Liping YANG ; Houkang CAO ; Xiaohui MA ; Ling JIN ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):194-202
In this paper, by consulting the ancient and modern literature, the name, origin, quality evaluation, harvesting and processing, and others of the original animal and medicinal materials of Moschus were systematically sorted out and verified, in order to provide the basis for the development and utilization of the famous classical formulas containing Moschus. According to the textual research, musk deer was first recorded in Shanhaijing. Shennong Bencaojing was recorded as Moschus and all generations were used as the correct name, but there were also aliases such as Shefu, Xiangzhang and Xiangqizi. In ancient times, Moschus berezovskii, M. sifanicus and M. moschiferus were the main sources of Moschus, and the quality of Moschus produced in northwest China was better than that produced in the Yangtze River basin. In modern times, Moschus of M. moschiferus produced in northeast China, M. sifanicus produced in Gansu, Sichuan and other places, and M. berezovskii produced in Ningxia, Shaanxi and other places are regarded as genuine. In ancient times, gunshots, lassoes, arrow shots and other methods were generally used to hunt live musk deer, and the sachets were immediately cut off. Those with high quality were called Xiangshanhuo, and dried in the shade after harvesting, which was known as Maoke Shexiang. Cut open the sachet, remove the shell and dry preservation, commonly known as Moschus kernel. In modern times, the method of taking Moschus from the living body of cultured musk deer is adopted, that is, Moschus kernel is directly taken from its sachet, dried in the shade or dried in a closed dryer. This method realizes the sustainable utilization of Chinese herbal medicine resources, but attention should be paid to the frequency and quality of Moschus. The harvesting time is mostly after the autumnal equinox every year, and before the next summer, it is better to gather sachet in winter. In recent times, it is believed that the shell Moschus is dry, full, thin, elastic, loose inside, many particles, strong and persistent aroma for the best, while the Moschus kernel is particle purple-black, powder yellow-brown, soft and oily texture, strong and persistent aroma for the best. The ancient processing method of Moschus was extracting kernels from the shell. After removing impurities, it is ground and used as medicine. Because its composition is not suitable for heating, the processing method is most common in preparations such as grinding into powder and putting into pills or powders, which has the effect of opening up the orifices and refreshing the mind, and it has continued to this day. Based on the research conclusions, it is suggested that the development of famous classical formulas containing Moschus, M. sifanicus, M. moschiferus and M. berezovskii should be used as the origins. According to the processing requirements specified in the original formula, it should be processed and used as medicine, while those without processing requirements should be used as raw products.
6.Clinical exploration of allogeneic PRP in refractory wound
Qiang TAN ; Ling WU ; Liping LIU ; Xinyu GAN ; Tao PENG
Chinese Journal of Blood Transfusion 2025;38(5):734-738
Objective: To explore the possibility of performing allogeneic platelet-rich plasma (PRP) treatment for patients who were not suitable for autologous PRP collection through case reports of two patients with refractory wounds treated with allogeneic PRP. Methods: The ABO-compatible allogeneic whole blood was centrifuged 3 times to obtain allogeneic PRP within 6 hours of blood collection. Then the qualified allogeneic PRP was applied to 2 cases of refractory wound on the same day. Results: The platelet concentration in allogeneic PRP was higher than 1 000×10
/L, and the test results of infectious diseases, as well as the mixing of red blood cells and white blood cells, met the standard of quality control. Both patients achieved satisfactory wound healing outcomes (3 d). Conclusions: For patients who were not suitable for autologous PRP treatment, allogeneic PRP might be a new option.
7.Changes in circulating levels of calcium and bone metabolism biochemical markers in patients receiving denosumab treatment.
Yuancheng CHEN ; Wen WU ; Ling XU ; Haiou DENG ; Ruixue WANG ; Qianwen HUANG ; Liping XUAN ; Xueying CHEN ; Ximei ZHI
Journal of Southern Medical University 2025;45(4):760-764
OBJECTIVES:
To investigate the changes in blood levels of calcium and bone metabolism biochemical markers in patients with primary osteoporosis receiving treatment with denosumab.
METHODS:
Seventy-three patients with primary osteoporosis treated in our Department between December, 2021 and December 2023 were enrolled. All the patients were treated with calcium supplements, vitamin D and calcitriol in addition to regular denosumab treatment every 6 months. Blood calcium, parathyroid hormone (PTH), osteocalcin (OC), type I procollagen amino-terminal propeptide (PINP), and type I collagen carboxy-terminal telopeptide β special sequence (β‑CTX) data before and at 3, 6, 9, and 12 months after the first treatment were collected from each patient.
RESULTS:
Three months after the first denosumab treatment, the bone turnover markers (BTMs) OC, PINP, and β-CTX were significantly decreased compared to their baseline levels by 39.5% (P<0.001), 56.2% (P<0.001), and 81.8% (P<0.001), respectively. At 6, 9, and 12 months of treatment, OC, PINP, and β-CTX remained significantly lower than their baseline levels (P<0.001). Blood calcium level was decreased (P<0.05) and PTH level increased (P<0.05) significantly in these patients at months of denosumab treatment, but their levels were comparable to the baseline levels at 6, 9, and 12 months of the treatment (P>0.05).
CONCLUSIONS
Denosumab can suppress BTMs and has a good therapeutic effect in patients with primary osteoporosis, but reduction of blood calcium and elevation of PTH levels can occur during the first 3 months in spite of calcium supplementation. Blood calcium and PTH levels can recover the baseline levels as the treatment extended, suggesting the importance of monitoring blood calcium and PTH levels during denosumab treatment.
Humans
;
Denosumab/therapeutic use*
;
Calcium/blood*
;
Parathyroid Hormone/blood*
;
Biomarkers/blood*
;
Osteoporosis/blood*
;
Osteocalcin/blood*
;
Procollagen/blood*
;
Female
;
Collagen Type I/blood*
;
Peptide Fragments/blood*
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Bone Density Conservation Agents/therapeutic use*
;
Bone and Bones/metabolism*
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Male
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Middle Aged
;
Vitamin D
;
Peptides/blood*
;
Aged
8.Effect of cholesterol on distribution, cell uptake, and protein corona of lipid microspheres at sites of cardiovascular inflammatory injury.
Lingyan LI ; Xingjie WU ; Qianqian GUO ; Yu'e WANG ; Zhiyong HE ; Guangqiong ZHANG ; Shaobo LIU ; Liping SHU ; Babu GAJENDRAN ; Ying CHEN ; Xiangchun SHEN ; Ling TAO
Journal of Pharmaceutical Analysis 2025;15(7):101182-101182
Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, overshadowing its influence on the biological effects of formulations. In this study, we reevaluated the delivery effect of CH using widely applied lipid microspheres (LM) as a model DDS. We conducted comprehensive investigations into the impact of CH on the distribution, cell uptake, and protein corona (PC) of LM at sites of cardiovascular inflammatory injury. The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage. Then, the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy. Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in vascular endothelial cells and estrogen receptor alpha (ERα) protein levels in myocardial cells, thereby enhancing LM uptake at cardiovascular inflammation sites. Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V (Apoa5); this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites. It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations. The findings enhance the conceptualization of CH and LM delivery, providing novel strategies for investigating prescription factors' bioactivity.
9.Development and application of a non-pharmacological nursing intervention program based on enhanced recovery after surgery and wrist-ankle acupuncture for postoperative nausea and vomiting in gynecological laparoscopic surgery
Xiao WANG ; Ling MEI ; Jian WANG ; Liping YU
Chinese Journal of Modern Nursing 2025;31(33):4578-4583
Objective:To develop a non-pharmacological nursing intervention program based on enhanced recovery after surgery (ERAS) and wrist-ankle acupuncture for postoperative nausea and vomiting (PONV) in gynecological laparoscopic surgery, and to evaluate its effectiveness.Methods:Through systematic literature retrieval, evidence screening, and expert consultation, a non-pharmacological intervention program for PONV based on ERAS and wrist-ankle acupuncture was established. Patients undergoing gynecological laparoscopic surgery in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January to May 2025 were selected using convenience sampling. The observation group received the ERAS and wrist-ankle acupuncture-based intervention program, while the control group received sham acupuncture on the basis of routine nursing care. The Rhodes Index of Nausea, Vomiting, and Retching (R-INVR) , the Postoperative Patient Comfort Scale (PPCS) , adverse event incidence, and patient satisfaction were used to evaluate intervention effects.Results:A total of 96 patients completed the study, including 49 in the observation group and 47 in the control group. After the intervention, 13 patients in the observation group and 23 in the control group had R-INVR scores ≥4, with a statistically significant difference between groups ( P<0.05) . The PPCS score was (70.76±16.11) in the observation group and (61.09±12.24) in the control group, with a significant difference ( t=3.321, P<0.05) . Patient satisfaction was higher in the observation group than in the control group ( P<0.05) . During the treatment period, all patients had stable vital signs, and no serious adverse reactions or allergic responses to drugs or acupuncture were observed. Conclusions:The ERAS and wrist-ankle acupuncture-based non-pharmacological nursing intervention program is reasonable and effective. From the perspective of patient safety, it can reduce the severity of PONV in gynecological laparoscopic surgery and improve patient comfort and satisfaction.
10.A multicenter study on pioneering symptoms of gastrointestinal symptom cluster in 463 gastric cancer patients with chemotherapy
Chao XIA ; Peibei DUAN ; Liping YANG ; Chaonan FEI ; Ziyan ZHANG ; Yanling ZOU ; Yi LI ; Ling YANG
Journal of Clinical Medicine in Practice 2025;29(2):124-128,137
Objective To explore the pioneering symptoms of the gastrointestinal symptom cluster and their influencing factors in gastric cancer patients with chemotherapy.Methods Based on the hospital's management system for scientific research data,463 gastric cancer patients with chemothera-py were surveyed through multicenter collaboration by the corresponding module of the MD Anderson Symptom Inventory(MDASI),the Chinese Medicine Constitution Classification and Identification Standard,and the Chinese Medicine SyndromeIdentification Standard for Gastric Cancer.IBM SPSS Statistic 22.0 and IBM SPSS Modeler 18.0 were used for data analysis.Results The first occurrence of dry mouth in the gastrointestinal symptom cluster of gastric cancer patients with chemotherapy was(22.99±10.70)hours after chemotherapy.The support,confidence,and lift for the association be-tween dry mouth and decreased appetite were 62.2%,94.8%and 1.52,respectively;for dry mouth and nausea,the numerical values were 62.2%,89.6%and 1.44;for dry mouth and vomiting,the numerical values were 62.2%,79.5%and 1.28.The results of one-way ANOVA and multivariate linear regression analysis showed that alcohol consumption,syndrome of stomach heat injuring yin,and phlegm-dampness constitution were independent influencing factors for dry mouth in gastric cancer patients with chemotherapy(P<0.05).Conclusion Dry mouth,as a pioneering symptom of the gastroin-testinal symptom cluster,is of great significance in clinical assessment and management.Improved assessment of dry mouth can provide a basis for the construction of subsequent risk prediction model,the formulation of targeted interventions,and the enhancement of symptom management efficiency.

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