BACKGROUND:Human periodontal ligament stem cells are potential functional cells for periodontal tissue engineering.However,long-term in vitro culture may lead to reduced stemness and replicative senescence of periodontal ligament stem cells,which may impair the therapeutic effect of human periodontal ligament stem cells. OBJECTIVE:To investigate the effect of oxymatrine on the stemness maintenance and osteogenic differentiation of periodontal ligament stem cells in vitro,and to explore the potential mechanism. METHODS:Periodontal ligament stem cells were isolated from human periodontal ligament tissues by tissue explant enzyme digestion and cultured.The surface markers of mesenchymal cells were identified by flow cytometry.Periodontal ligament stem cells were incubated with 0,2.5,5,and 10 μg/mL oxymatrine.The effect of oxymatrine on the proliferation activity of periodontal ligament stem cells was detected by CCK8 assay.The appropriate drug concentration for subsequent experiments was screened.Western blot assay was used to detect the expression of stem cell non-specific proteins SOX2 and OCT4 in periodontal ligament stem cells.qRT-PCR and western blot assay were used to detect the expression levels of related osteogenic genes and proteins in periodontal ligament stem cells. RESULTS AND CONCLUSION:(1)The results of CCK8 assay showed that 2.5 μg/mL oxymatrine significantly enhanced the proliferative activity of periodontal stem cells,and the subsequent experiment selected 2.5 μg/mL oxymatrine to intervene.(2)Compared with the blank control group,the protein expression level of SOX2,a stem marker of periodontal ligament stem cells in the oxymatrine group did not change significantly(P>0.05),and the expression of OCT4 was significantly up-regulated(P<0.05).(3)Compared with the osteogenic induction group,the osteogenic genes ALP,RUNX2 mRNA expression and their osteogenic associated protein ALP protein expression of periodontal ligament stem cells were significantly down-regulated in the oxymatrine+osteogenic induction group(P<0.05).(4)The oxymatrine up-regulated the expression of stemness markers of periodontal ligament stem cells and inhibited the bone differentiation of periodontal ligament stem cells,and the results of high-throughput sequencing showed that it may be associated with WNT2,WNT16,COMP,and BMP6.

ObjectiveTo observe the analgesic efficacy and safety of Qihuang acupuncture theory combined with opioid analgesics in patients with moderate to severe cancer pain due to lung cancer. MethodsPatients with moderate to severe cancer pain from lung cancer were randomly divided into Qihuang acupuncture group and control group， with 33 cases in each group. The control group was treated with long-acting opioid analgesics at maintenance doses and supplementary analgesic medications as needed. In case of breakthrough pain， short-acting opioids were used for rescue. The Qihuang acupuncture group received Qihuang acupuncture treatment in addition to the treatment used in the control group， administered once every other day， with 3 sessions constituting one treatment course. The treatment duration for both groups was 5 days. The primary outcome was the change in pain intensity， measured using the numerical rating scale （NRS） before and after treatment， and the NRS change rate was calculated. Secondary endpoints included the daily NRS change rate， the Eastern Cooperative Oncology Group （ECOG） Performance Status （PS） score， the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire （EORTC QLQ-C30） score， and the 24-hour equivalent hydrocodone sustained-release tablet dose. Laboratory tests， including routine blood， urine， stool， liver function， and kidney function， were performed before and after treatment. Adverse events were recorded throughout the trial. ResultsAll patients completed the trial， and both groups showed a decrease in average NRS scores and PS scores after treatment， with the Qihuang acupuncture group showing lower average NRS scores and PS scores than the control group （P＜0.05 or P＜0.01）. After treatment， the NRS change rate in the Qihuang acupuncture group was （0.42±0.17）， significantly higher than that in the control group （0.14±0.27， P＜0.01）. The daily NRS change rate during treatment was also higher in the Qihuang acupuncture group compared to the control group （P＜0.01）. The Qihuang acupuncture group showed an increase in overall health status and functional scores in the EORTC QLQ-C30， and a decrease in symptom scores for fatigue， nausea and vomiting， pain， dyspnea， insomnia， appetite loss， constipation， and financial difficulties. In contrast， overall health status and constipation scores in the control group increased， while scores of fatigue， nausea and vomiting， pain， and appetite loss decreased （P＜0.05 or P＜0.01）. After treatment， the 24-hour equivalent hydrocodone sustained-release tablet dose did not show significant difference in the Qihuang acupuncture group （P＞0.05）， while the control group showed a significant increase in the 24-hour dose （P＜0.01）. No significant abnormalities were observed in laboratory tests before and after treatment in either group. During the study， the incidence of nausea and vomiting as well as constipation in the Qihuang acupuncture group was both 3.03% （1/33）， while the incidence in the control group was 27.27% （9/33） and 36.36% （12/33）， respectively， with the Qihuang acupuncture group showing significantly lower incidence （P＜0.01）. No serious adverse reactions were observed in either group. ConclusionQihuang acupuncture therapy combined with opioid analgesics is more effective than using opioids alone in relieving pain in patients with moderate to severe cancer pain due to lung cancer. It can improve the patients' physical condition and quality of life， reduce the dose of opioid analgesics， and has good safety.

Objective To investigate the effects of 6-pyruvoyl-tetrahydropterin synthase(PTS)on gastric cancer cells.Methods The expression of PTS protein and mRNA in gastric mucosal epithelial cells GES-1 and gastric cancer cell lines HGC-27 cells,MGC-803 cells,AGS cells and MKN-45 cells were determined by Western blot(WB)and reverse transcription quantitative polymerase chain reaction(RT-qPCR).AGS cells were selected for follow-up experiments.AGS cells were divided into control(NC)group,sh-PTS group,and sh-PTS+BML-284 group.Cell proliferation was measured by CCK-8.Cell migration ability was measured by scratch healing.Cell invasion and migration were measured by Transwell assay.Apoptosis was measured by flow cytometry.The protein and mRNA levels of β-catenin,c-myc,GSK-3β and Wnt5a were detected by WB and RT-qPCR.Results The expression of PTS in gastric mucosal epithelial cells GES-1 was lower than that in gastric cancer cells,and the expression of PTS was the highest in AGS cells.Knocking down PTS could inhibit proliferation,migration and invasion of gastric cancer cells,promote cell apoptosis,decreased β-catenin,c-myc,Wnt5a protein levels,and increased GSK-3β protein levels(P＜0.05).Compared with sh-PTS group,cell proliferation,migration and invasion ability of sh-PTS+BML-284 group were enhanced,apoptosis level was decreased,protein expression of β-catenin,c-myc and Wnt5a was increased,and protein expression of GSK-3β was decreased(P＜0.05).Conclusion PTS can affect proliferation,migration,invasion and apoptosis of gastric cancer cells by mediating Wnt/β-catenin pathway.

Objective:To investigate the clinical characteristics and treatment mode changes of chronic pancreatitis (CP).Methods:The retrospective and descriptive study was conducted. The clinical data of 805 patients with CP who were admitted to the First Affiliated Hospital of Xi′an Jiaotong University from January 2013 to December 2022 were collected. There were 575 males and 230 females, aged 52(range, 10-87)years. Observation indicators: (1)demographic characteristics; (2)distribution of admission departments, hospitalization and treatment status. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distri-bution were represented as M(range). Count data were expressed as absolute numbers and percentages. The chi-square goodness-of-fit test was used for consistent between expected frequency and empirical distribution. Results:(1)Demographic characteristics. Of the 805 patients, there were 435 cases and 370 cases diagnosed as CP according to the primary and secondary diagnostic criteria, respec-tively, and the age of initial presentation of 805 patients was 52(range, 10-87)years. Among male and female patients, there was 1 and 0 case in the age group of 0-10 years, there were 16 and 14 cases in 11-20 years, 45 and 26 cases in 21-30 years, 82 and 30 cases in 31-40 years, 122 and 39 cases in 41-50 years, 157 and 51 cases in 51-60 years, 119 and 46 cases in 61-70 years, 31 and 21 cases in 71-80 years, 2 and 3 cases in 81-90 years, respectively. Patients aged 0-14, 15-34, 35-64, and ≥65 years were 0, 6, 28, and 9 for 2013, 1, 21, 34, and 10 for 2014, 1, 8, 38, and 7 for 2015, 0, 7, 52, and 10 for 2016, 0, 11, 35 and 9 for 2017, 1, 15, 72 and 23 for 2018, 0, 9, 55 and 11 for 2019, 2, 19, 58 and 16 for 2020, 0,20, 79 and 18 for 2021, 0, 25, 73 and 22 for 2022, respectively. Of the 805 patients, cases from Shaanxi Province, Gansu Province and other regions were 702, 48 and 55, respectively. There are 802 Han and 3 Hui patients, respectively, and the married, unmarried, divorced, and widowed patients were 732, 64, 7, and 2, respectively. Cases with blood type information was 682, with the distribution of blood types as 26.10%(178/682) of type A, 34.46%(235/682)of type B, 9.97%(68/682) of type AB, 29.47%(201/682)of type O, showing no significant difference compared to the distribu-tion of blood types in population of Shaanxi Province in 2022 (28.43% of type A, 30.50% of type B, 9.83% of type AB, and 30.50% of type O) ( χ2=0.50, P>0.05). (2)Distribution of departments, hospita-lization, and treatment. Of the 805 patients, cases admitted to the Department of Hepatobiliary Surgery, Department of Gastroenterology and other departments (Department of Geriatric Surgery, Infectious Diseases and General Surgery) were 594, 121 and 90, respectively. Cases of the number of hospitalizations in the Department of Hepatobiliary Surgery, Department of Gastroenterology and other departments were 771, 121 and 94, respectively. One patient might have been admitted for multiple times. The duration of hospital of stay of 805 patients was 11(rang, 1-67)days. The duration of hospital stay of patients admitted to the Department of Hepatobiliary Surgery, Department of Gastroenterology and other departments were 16(range, 2-48)days, 11(range, 5-19)days and 24(range, 12-35)days for 2013, 18(range, 2-63)days, 10(range, 3-29)days and 14(range, 7-30)days for 2014, 9(range, 1-35)days, 11(range, 2-16)days and 10(range, 5-33)days for 2015, 10(range, 1-55)days, 9(range, 4-16)days and 16(range, 4-27)days for 2016, 9(range, 2-38)days, 10(range, 4-20)days and 11(range, 5-27)days for 2017, 12(range, 3-46)days, 11(range, 2-26)days and 13(range, 7-27)days for 2018, 11(range, 1-33)days, 9(range, 3-23)days and 14(range, 4-17)days for 2019, 11(range, 1-67)days, 7(range, 1-23)days, and 16(range, 4-27)days for 2020, 10(range, 1-35)days, 8(range, 1-32)days and 14(range, 1-29)days for 2021, 9(range, 1-42)days, 12(range, 3-17)days and 11(range, 1-22)days for 2022. Of the 805 patients, cases receiving treatment as surgical treatment, pancreas extracorporeal shock wave lithotripsy (P-ESWL), endoscopic treatment and other treatments were 258, 117, 194 and 236, respectively. A total of 260 surgeries were performed on 258 patients receiving surgical treatment, and there were 236 cases receiving surgical treatment as the first choice, and 22 cases undergoing surgery after failed of other treatments. The surgical procedures included pancreaticoduodenectomy in 79 cases, distal pancreatectomy (with or without splenectomy, Peustow procedure) in 35 cases, partial pancreatectomy with pancreatic duct incision and stone removal and pancreaticojejunostomy in 77 cases, simple pancreatic duct incision and pancreaticojejunostomy in 58 cases, internal drainage for pancreatic pseudocysts in 4 cases, and drainage for removal of pancreatic necrotic tissue in 7 cases. There were 58 patients with post-operative complications, including 9 cases of bleeding, 19 cases of infection, 2 cases of gastric paresis, 21 cases pancreatic fistula, and 7 cases of intestinal leakage. Cases with postoperative complications were recovered and discharged after symptomatic treatment. Of the 117 patients receiving P-ESWL, the times of treatment per patient was 1.3±0.7, and a total of 154 times of P-ESWL were performed. There were 89 patients receiving one time of P-ESWL, and 28 patients receiving ≥2 times of P-ESWL. Of the 194 patients receiving endoscopic treatment, the times of treatment per patient was 1.2±0.6, and a total of 238 times of endoscopic treatment were performed. There were 103 cases receiving stent placement, 43 cases receiving nasopancreatic/nasobiliary drainage, 7 cases receiving pancreatic duct balloon dilation, 71 cases receiving pancreatic stone removal, and 58 cases receiving duodenal papilla sphincterotomy. There were 168 patients receiving one time of endoscopic treatment, and 26 patients receiving ≥2 times of endoscopic treatment.There was no postoperative complica-tions reported. Conclusions:The proportion of males in CP patients is relatively high, and the proportion gradually increases with age of 51-60 years. There is no significant difference in the distribution of blood types among CP patients and the population of Shaanxi Province. The proportion of minimally invasive treatment (extracorporeal shock wave lithotripsy and endoscopic therapy) in CP treatment is on the rise, and the duration of hospital stay for patients is on the decline.

Existing studies have shown that Astragalus membranaceus(AM)and its active ingredients astragalus polysaccharides,oninon,and astragalus methyl glycosides can attenuate X-ray radiation-induced injury.However,there are no studies on how isoliquiritigenin(ISL)attenuate the bystander effect of bone marrow mesenchymal stem cells(BMSCs)induced by carbon ion radiation therapy for lung cancer.This study aimed to investigate the AM-derived small molecule ISL to enhance radiotherapy sensitivity by attenuating the carbon ion radiation-induced bystander effect(RIBE)in BMSCs to elucidate its mecha-nism of action.In this study,we established a C57BL/6 mouse lung cancer transplantation tumor model in vivo and a co-culture model of A549 cells and BMSCs in vitro,and the models were successfully treated with carbon ions.In further work,we used flow cytometry,immunofluorescence,Western blot,enzyme-linked immunosorbent assay(ELISA),inhibitor,short hairpin RNA(shRNA),Cell Counting Kit-8(CCK-8),and other methods to illustrate the mechanism.In the next experiments,we found that ISL combined with carbon ion radiotherapy had a significant anti-tumor effect and protected BMSCs from radiation damage.The aim of this study was to investigate the potential of ISL in enhancing the sensitivity of lung cancer cells to radiotherapy and attenuating RIBE in both in vitro and in vivo settings.Traditional Chinese medicine combined with radiation therapy is a promising and innovative treatment for non-small cell lung cancer.These results establish a theoretical foundation for further clinical development of ISL as a potential radiosensitizer option.

It has been proposed by Basic Questions On Proper Therapies for Different Diseases Geographically （《素问·异法方宜论篇》） that "wei （痿） diseases should be treated by Daoyin （导引）". Furthermore， it is clarified that the indications of Daoyin are those conditions related to spleen and dampness caused by dampness pathogen， excessive food intake and less exercise， and mainly manifested as heavy limbs， fatigue and flaccidity， which is similar to the metabolic imbalance in the early stage of glucose or lipid metabolism disorder in modern medicine. Based on modern clinical and basic research evidence， Daoyin can inhibit the response of inflammation， alleviate oxidative stress， regulate intestinal microbiota， and modulate gene expression to improve metabolic abnormalities， and this will provide ideas for researches on the indications of Daoyin.

【Objective】 To examine risk factors for acute pancreatitis (AP) in individuals with chronic alcohol consumption habits. 【Methods】 The study incorporated participants from the initial survey (2006-2010) and subsequent follow-ups (2014+) taken from the UK Biobank database, with the observation period ending on November 30, 2022. During this period, 176 individuals were newly diagnosed with AP, while 59,512 remained unaffected. Vital characteristics of the target population, such as their medical histories, surgical experiences and dietary patterns, were collected during the enrolment phase (2006-2010). The Cox proportional hazard model was employed to ascertain whether these characteristics were potent risk factors for AP. Concurrently, a subgroup from the target population with documented drinking behavior was selected. The multivariate Cox proportional hazard model was utilized to analyze the relationship of the established factors, variances in alcohol consumption, and increased alcohol intake (Δ) with the onset of AP, and whether the additional alcohol intake served as a risk factor. 【Results】 Multivariate analysis revealed that consumption quantity of cooked vegetables inversely correlated with AP risk (HR=0.44, 0.39, 0.42 and 0.41 for one, two, three and four+ tablespoons per day, respectively, as compared to non-consumers). Coffee consumption (2-3 cups per day) also reduced AP risk (HR=0.45 for 2 cups/day; HR=0.39 for 3 cups/day as compared to non-coffee drinkers). However, those with biliary disease without cholecystectomy exhibited a marked increase in AP risk (HR=7.82), which reduced albeit remained elevated for those with biliary disease post-cholecystectomy (HR=2.15). Subgroup analysis showed minimal impact of alcohol intake levels on AP incidence. Yet, increased alcohol consumption (Δ of 1 bottle/week) was linked to a heightened AP risk (HR=1.05, 95% CI:1.02-1.09, P<0.05). 【Conclusion】 Among longstanding alcohol consumers, a diet rich in cooked vegetables and moderate coffee consumption offers protective effects against AP. Conversely, biliary disease (particularly without cholecystectomy) and elevated alcohol intake present considerable risk factors for the development of this condition.

OBJECTIVE To screen potential adverse drug event （ADE） signals for the treatment of multiple sclerosis （MS） with ofatumumab， and to provide reference for the safe use of drugs in clinical practice. METHODS Using “ofatumumab” and the trade name “Kesimpta” as the search keywords， adverse event （AE） reports related to ofatumumab included in FDA Adverse Event Reporting System database from January 2009 to December 2023 were screened， and their reason contained the “multiple sclerosis”； ADE signal mining and analysis were conducted by reporting odds ratio method and proportional reporting ratio method. RESULTS A total of 21 759 eligible AE reports were selected， involving 62 449 AE cases； 27 system organ classes included general diseases and various reactions at the site of administration （15 021 cases）， neurological diseases （9 668 cases）， infectious and invasive diseases （5 967 cases）， injury， poisoning and surgical complications （4 952 cases）， musculoskeletal and connective tissue disorders （4 647 cases）. A total of 21 759 AE reports correspond to 606 ADE signals， including 234 ADE positive signals. A total of 107 ADE positive signals were not included in drug instruction of ofatumumab， including flu-like diseases， nasopharyngitis， cough， urinary tract infection， sore throat， insomnia， runny nose， anemia， hair loss， atrial fibrillation， and thrombocytopenia， etc. CONCLUSIONS In the process of using ofatumumab for MS， sufficient attention should be paid to ADE included in drug instructions. The ADE with strong signal strength screened in this study should also be paid special attention to， such as flu-like diseases， hemocytopenia， temperature intolerance， optic neuritis， and moyamoya disease. The increased risk of infection， cardiovascular disease， and potential damage to the respiratory and spiritual systems caused by ofatumumab can not be ignored.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Objective:To compare the clinical efficacies of O-arm combined with CT three-dimensional navigation system assisted screw placement versus manual screw placement in treating lower cervical fracture and dislocation.Methods:A retrospective cohort study was used to analyze the clinical data of 41 patients with lower cervical fracture and dislocation, who were treated in Honghui Hospital, Xi′an Jiaotong University from May 2021 to February 2022. The patients included 26 males and 15 females, aged 31.5-48.6 years [(41.5±15.0)years]. The injured segments were C 3 in 3 patients, C 4 in 12, C 5 in 13, C 6 in 10 and C 7 in 3. Nineteen patients were treated with cervical pedicle screws by O-shaped arm combined with CT three-dimensional navigation system (navigation group, 76 screws) and 22 by bare hands (traditional group, 88 screws). The total operation time, effective operation time, single nail placement time, single screw correction times, screw distance from anterior cortex, intraoperative blood loss, intraoperative fluoroscopic radiation dose, incision length and length of hospital stay were compared between the two groups, and the height of intervertebral space, Cobb angle, interbody slip distance and American Spinal injury Association (ASIA) grade were compared before operation and at 3 days after operation. Visual analogue score (VAS), Japanese Orthopedic Association (JOA) score, and neck dysfunction index (NDI) were evaluated before operation, at 3 days, 3 months after operation and at the last follow-up. Accuracy of screw placement and incidence of complications (adjacent facet joint invasion, infection, screw loosening) were detected as well. Results:All the patients were followed up for 11.1-13.9 months [(12.5±1.4)months]. The total operation time, intraoperative blood loss, intraoperative fluoroscopic radiation dose and incision length in the navigation group were more or longer than those in the traditional group (all P<0.05). The effective operation time, single nail placement time, single nail correction times and screw distance from anterior cortex in the navigation group were markedly less or smaller than those in the traditional group (all P<0.05). There was no significant difference in the length of hospital stay between the two groups ( P>0.05). There were significant improvements in the height of intervertebral space, Cobb angle and interbody slip distance between the two groups at 3 days after operation (all P<0.05). There was no significant difference in the height of intervertebral space, Cobb angle, interbody slip distance or ASIA grade between the two groups before operation or at 3 days after operation (all P>0.05). Compared with pre-operation, the VAS, JOA score and NDI were significantly improved in both groups at 3 days, 3 months after operation and at the last follow-up (all P<0.05), with further improvement with time. There was no significant difference in VAS between the two groups before operation or at 3 months after operation (all P>0.05), but it was markedly lower in the navigation group compared with the traditional group at 3 days after operation and at the last follow-up (all P<0.05). There were no significant differences in JOA score or NDI between the two groups before operation or at 3 days and 3 months after operation (all P>0.05), but both were lower in the navigation group compared with the traditional group at the last follow-up (all P<0.05). The accuracies of placement of grade 0 and grade 0+1 screws were 92.0% (70/76) and 96.6% (73/76) in the navigation group, respectively, which were markedly higher than 88.7% (78/88) and 93.5% (82/88) in the traditional group (all P<0.05). The rates of adjacent facet joint invasion of A, B, and C degrees were 71.2% (54/76), 28.8% (22/76) and 0% (0/76) in the navigation group, respectively, while the invasion rates were 60.5% (53/88), 32.3% (28/88) and 7.3% (7/88) in the traditional group ( P<0.05). No screw loosening was noted in the navigation group, but the screw loosening rate was 9.1% (8/88) in the traditional group ( P<0.01). Conclusion:Compared with manual screw placement, O-arm combined with CT three-dimensional navigation system assisted screw placement for lower cervical fracture and dislocation has the advantages of shorter effective operation time, quicker screw placement, stronger screw holding force, better cervical stability, slighter postoperative pain, higher screw placement accuracy, and lower facet joint invasion and screw loosening rates.