ObjectiveTo investigate the changing trends of the incidence rate， prevalence rate， mortality rate， and disability-adjusted life years （DALYs） of benign hepatobiliary and pancreatic diseases among people aged 15 — 39 years in China in 1990 — 2021. MethodsThe data of 2021 Global Burden of Disease Study were downloaded to obtain the epidemiological data of liver fibrosis/chronic liver disease， benign gallbladder/biliary tract diseases， and pancreatitis among people aged 15 — 39 years in China， and estimated annual percentage change （EAPC） was calculated to assess the changing trends of incidence， prevalence， mortality， and DALY rates. The Bayesian age-period-cohort model was used to predict the incidence and mortality rates from 2022 to 2030. ResultsIn 2021， there were 10 448 778 new cases of benign hepatobiliary and pancreatic diseases among the individuals aged 15 — 39 years in China， which was increased by 3.8% compared with the data in 1990， while the numbers of prevalent cases， deaths， and DALYs were reduced by 20.4%， 59.6%， and 50.2%， respectively. In 2021， the age-standardized incidence rates of liver fibrosis/chronic liver disease， benign gallbladder/biliary tract diseases， and pancreatitis were 1 104.40/100 000， 1 045.05/100 000， and 16.64/100 000， respectively； the age-standardized prevalence rates were 20 592.37/100 000， 2 364.85/100 000， and 9.43/100 000， respectively； the age-standardized mortality rates were 1.61/100 000， 0.04/100 000， and 0.18/100 000， respectively. From 1990 to 2021， there was a tendency of increase in the age-standardized incidence rate of liver fibrosis/chronic liver disease （EAPC=0.43， 95% confidence interval ［CI］： 0.23 — 0.63）， and there was also a tendency of increase in the age-standardized incidence and prevalence rates of benign gallbladder/biliary tract diseases （incidence rate： EAPC=1.07， 95%CI： 0.91 — 1.24； prevalence rate： EAPC=0.75， 95%CI： 0.59 — 0.89）， while there was a tendency of reduction in the age-standardized mortality rate of all three disease categories. Predictions for 2022 — 2030 indicated a potential reduction in the incidence rate of benign gallbladder/biliary tract diseases and an increase in the incidence rate of pancreatitis. ConclusionThere has been an overall upward trend in the incidence rate of liver fibrosis/chronic liver disease and gallbladder/biliary tract diseases over the past three decades， and it is needed to pay attention to the disease burden of benign hepatobiliary diseases among the people aged 15 — 39 years in China.

[摘 要] 目的：探讨复发/转移性鼻咽癌（NPC）接受含PD-1单抗免疫治疗的临床特征和预后影响因素。方法：回顾性分析2019年3月至2024年7月期间南部战区总医院确诊的95例NPC患者的临床资料和外周血生化及免疫学指标。预后分析采用Kaplan-Meier曲线，组间比较使用Log-rank检验，采用Cox比例风险模型进行单因素和多因素分析。结果：95例患者中男性81例，女性14例，中位年龄49.72岁（16~74岁），Ⅳ期91例（95.79%），所有患者均采用免疫治疗，联合或不联合化疗方案治疗，中位无进展生存期（mPFS）为10.5个月，客观缓解率（ORR）70.53%，疾病控制率（DCR）89.47%，接受含铂治疗方案患者PFS相对更长，且差异有统计学意义。紫杉醇 + 顺铂 + 氟尿嘧啶（TPF）对比吉西他滨 + 顺铂（GP）和紫杉醇 + 顺铂（TP）显示出更长的PFS，但差异无统计学意义。不同PD-1单抗治疗组间的PFS未显示出有统计学意义的差异。单因素及多因素Cox回归分析结果显示，肿瘤复发状态、初始血浆EBV感染状态、治疗周期数、基线外周血SII是复发/转移性NPC患者接受PD-1抑制剂治疗疗效预测的独立相关因素（均P < 0.05），并且非复发患者、初始血浆EBV DNA阳性、接受 ≥ 4治疗周期、基线外周血SII < 772.81的患者接受PD-1抑制剂治疗预后相对更好。结论：在接受PD-1抑制剂治疗的复发/转移性NPC患者中，非复发患者、初始血浆EBV DNA阳性、≥ 4治疗周期且外周血SII < 772.81者PFS相对更长，可早期识别免疫治疗效果不佳患者并精准干预。

ObjectiveThis paper aims to investigate the effects and mechanism of Mimenghua prescription in modulating the mitogen-activated protein kinase kinase （MEK）/rat sarcoma viral oncogene homolog （Ras）/rapidly accelerated fibrosarcoma kinase （Raf）/extracellular signal-regulated kinase （ERK） signaling pathway to inhibit inflammatory responses in a dry eye animal model. MethodsA total of 60 C57BL/6J mice （eight weeks old， half male and half female） were used in the experiment. Ten mice were randomly selected as the blank control group， while the remaining 50 were exposed to a controlled dry system and received instillation of 0.2% benzalkonium chloride （BAC） into the eyes for four weeks to establish a dry eye mouse model. After successful modeling， the mice were randomly divided into five groups： Model group， sodium hyaluronate group， and Mimenghua prescription groups with low dose （4.83 g·kg^-1）， medium dose （9.67 g·kg^-1）， and high dose （19.34 g·kg^-1）. The mice in the model group received an equal volume of normal saline via gavage for four weeks. The mice in the sodium hyaluronate group received instillation of sodium hyaluronate eye drops twice daily for 14 consecutive days. The tear secretion volume， tear film break-up time （TBUT）， and corneal fluorescein staining were evaluated once every two weeks. After four weeks of administration， mice were euthanized， and their lacrimal gland tissues and corneas were harvested. Hematoxylin-eosin （HE） staining was used to assess histopathological morphology. Western blot was performed to detect the protein expression levels of MEK， Ras， Raf， and ERK. Enzyme-linked immunosorbent assay （ELISA） was used to measure the contents and expressions of MEK， Ras， Raf， ERK， and interleukin （IL）-1β in lacrimal gland and corneal tissues of the mice in each group. Quantitative real-time polymerase chain reaction （Real-time PCR） was employed to determine mRNA expression levels of MEK， Ras， Raf， and ERK. ResultsThe Mimenghua prescription groups and the sodium hyaluronate group exhibited significantly increased tear secretion volume （P<0.05） and prolonged TBUT （P<0.05） after treatment. Ocular surface damage of mice was visibly recovered. Western blot results indicated that protein expression levels of MEK， Ras， Raf， and ERK in the lacrimal gland and corneal tissues were significantly downregulated in the sodium hyaluronate group and Mimenghua prescription group with high dose （P<0.05）. ELISA results showed that IL-1β levels were highest in the model group but significantly reduced in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）. Both ELISA and Real-time PCR results demonstrated that the expression levels of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues were significantly elevated in the model group （P<0.05）， but markedly downregulated in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）， suggesting that Mimenghua prescription can decrease the expressions of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues. ConclusionMimenghua prescription can reduce inflammatory responses， increase tear secretion， prolong TBUT， and promote corneal recovery by inhibiting the MEK， Ras， Raf， and ERK signaling pathways in lacrimal gland and corneal tissues.

BACKGROUND:Magnetic resonance imaging is the gold standard for the diagnosis of osteonecrosis of femoral head,and previous methods of predicting osteonecrosis of femoral head collapse based on magnetic resonance images mostly require the combined assessment of coronal and sagittal images.However,osteonecrosis of femoral head tends to occur bilaterally,most hospitals perform bilateral hip magnetic resonance imaging scans during clinical examinations,but the bilateral hip scans can only view coronal and cross-sectional images,and it is difficult to obtain sagittal images,which affects the assessment of the risk of collapse.Therefore,it is of clinical value to establish a method to assess the risk of early osteonecrosis of femoral head collapse by applying the images that can be obtained after bilateral hip magnetic resonance scanning. OBJECTIVE:To establish a method of applying coronal and cross-sectional images of bilateral hip magnetic resonance imaging to assess the risk of osteonecrosis of femoral head collapse. METHODS:The medical records of 111 patients(181 hips)with early-stage osteonecrosis of femoral head diagnosed at the outpatient clinic of Honghui Hospital Affiliated to Xi'an Jiaotong University from October 2017 to October 2019 were retrospectively analyzed.They were categorized into collapsed and non-collapsed groups according to the femoral head collapse at the final follow-up,with 69 hips in the collapsed group and 112 hips in the non-collapsed group.The angle of necrotic range on the images of median coronal plane,transverse plane or one level above and below it was measured on the magnetic resonance imaging system.The sum of the two angles of necrotic angle on the coronal and transverse planes was used as the combined necrotic angle.The average of the three combined necrotic angles of each hip was taken to get the average combined necrotic angle of each hip.Finally,the correlation between the three combined necrotic angles and the average combined necrotic angle with the collapse of osteonecrosis of femoral head was analyzed,and the specificity and sensitivity of the four combined necrotic angles in predicting collapse were evaluated by using receiver operating characteristic curves. RESULTS AND CONCLUSION:(1)Totally 69 hips(38.1%)had femoral head collapse at the last follow-up and were included in the collapsed group;112 hips(61.9%)did not have progression of collapse and were included in the non-collapsed group.(2)The difference between the collapsed group and the non-collapsed group in terms of Association Research Circulation Osseous(ARCO)stage was significant(P<0.001).The difference in age,body mass index,follow-up time,gender distribution,side of onset,and causative factors was not significant(P>0.05).(3)The results of independent samples t-test suggested that all four combined necrotic angles were significantly correlated with collapse(P<0.000 1);and the differences in combined necrotic angles between the collapsed group and the non-collapsed group of ARCO stage I and the two groups of ARCO stage II were all significant(P<0.000 1).(4)In the analysis of the receiver operating characteristic,the area under the curve of the average combined necrotic angle was greater than that of the combined necrotic angle on the lower level of the median,the middle level,and the upper level of the median.(5)The average combined necrotic angle had a higher accuracy in the prediction of collapse than the lower level of the median,the middle level,and the upper level of the combined necrotic angle.(6)It is concluded that the accuracy of the average combined necrotic angle in predicting the risk of osteonecrosis of femoral head collapse is higher,and the clinical practicability is stronger,so we can consider using this method to predict the risk of osteonecrosis of femoral head collapse.

BACKGROUND:Ilizarov bone transport is very effective in the treatment of open large tibial bone defects,but there are still complications,among which the difficulty of junction healing is one of the difficult points in treatment. OBJECTIVE:To investigate the effect of Ilizarov bone transport combined with antibiotic bone cement on junction healing after operation of open large tibial bone defect. METHODS:Totally 51 patients with open large tibial bone defect(bone defect>4 cm)admitted to Binzhou Medical University Hospital from August 2010 to January 2022 were selected,of which 28 received Ilizarov bone transport alone(control group)and 23 received Ilizarov bone transport combined with antibiotic bone cement treatment(trial group).External fixation time,bone healing time,bone healing index,visual analog scale score during bone removal,bone defect limb function,junction healing and complications at the final follow-up were statistically compared between the two groups. RESULTS AND CONCLUSION:(1)All the 51 patients were followed up for a mean of(22.53±5.77)months.External fixation time,bone healing time,bone healing index,postoperative infection rate,and non-healing rate of junction were less in the trial group than those in the control group(P<0.05).There was no significant difference between the two groups in visual analog scale scores at 6 months after the second surgery and in the functional excellence and good rate of limb with bone defect at the final follow-up(P>0.05).(2)These findings indicate that compared with the Ilizarov bone transport alone,Ilizarov bone transport combined with antibiotic bone cement treatment can promote the healing of open tibial fracture junction and increase the rate of bone healing.

ObjectiveTo explore the effect of Buzhong Yiqitang on exercise-induced fatigue and its potential mechanism. MethodsSixty male SPF-grade C57BL/6J mice were randomized into blank， model， low-， medium-， high-dose （4.1， 8.2， 16.4 g·kg^-1， respectively） Buzhong Yiqitang， and vitamin C （0.04 g·kg^-1） groups. The blank and model groups were administrated with normal saline. Each group was administrated with corresponding agents by gavage at a dose of 0.2 mL once a day. Except the blank group， other groups underwent a 6-weeks exhaustive swimming test under negative gravity. At the end of the experiment， blood was collected， and the thymus， spleen， liver， and kidney weights were measured. Serum levels of lactic acid （LD）， blood urea nitrogen （BUN）， creatine kinase （CK）， and malondialdehyde （MDA） were assessed by kits to evaluate fatigue. Hematoxylin-eosin staining was performed to observe pathological changes in the skeletal muscle. Electron microscopy was used to examine the skeletal muscle cell ultrastructure， with a focus on mitochondrial morphological changes. The adenosine triphosphate （ATP） content and activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ in skeletal muscle were determined by kits. The expression levels of key genes and proteins in the PTEN-induced putative kinase 1 （PINK1）-mediated mitochondrial homeostasis pathways in the skeletal muscle were evaluated via Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the model group showed reductions in weight gain rate （P<0.01） and thymus index （P<0.01）， rises in serum levels of LD， BUN， MDA， and CK （P<0.01）， disarrangement of skeletal muscle， broken muscle fibers， inflammatory cell infiltration in muscle fiber gaps， abnormal morphological changes （increased vacuolated mitochondria and disappearance of cristae） of mitochondria in skeletal muscle cells， and decreased mitochondria. In addition， the skeletal muscle in the model group showed reduced content of ATP， weakened activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ （P<0.05）， up-regulated mRNA levels of PINK1， E3 ubiquitin-protein ligase （Parkin）， hairy/enhancer-of-split related with YRPW motif 1 （HEY1）， dynamin-related protein 1 （Drp1）， sequestosome 1 （p62）， and hypoxia-inducible factor 1 alpha （HIF-1α） （P<0.05）， and down-regulated protein level of microtubule-associated protein 1-light chain 3B （LC3B） （P<0.01）. Compared with the model group， Buzhong Yiqitang prolonged the swimming exhaustion time （P<0.01）， increased the weight gain rate （P<0.01） and thymus index （P<0.01）， lowered the serum levels of LD， BUN， MDA， and CK （P<0.05， P<0.01）. The skeletal muscle in the Buzhong Yiqitang groups showed neat arrangement， reduced inflammatory cells， intact mitochondria with dense cristae， and increased mitochondria. In addition， the skeletal muscle in the Buzhong Yiqitang groups showcased increased ATP content， enhanced activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ （P<0.05， P<0.01）， up-regulated protein levels of PINK1， Parkin， HEY1， LC3B， and Drp1 and mRNA level of HIF-1α （P<0.05， P<0.01）， and down-regulated expression level of p62 （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can prevent and treat exercise-induced fatigue by regulating the mitochondrial homeostasis of skeletal muscle via the HIF-1α/PINK1/Parkin and HIF-1α/HEY1/PINK1 signaling pathways.

ObjectiveTo explore the effect of Buzhong Yiqitang on exercise-induced fatigue and its potential mechanism. MethodsSixty male SPF-grade C57BL/6J mice were randomized into blank， model， low-， medium-， high-dose （4.1， 8.2， 16.4 g·kg^-1， respectively） Buzhong Yiqitang， and vitamin C （0.04 g·kg^-1） groups. The blank and model groups were administrated with normal saline. Each group was administrated with corresponding agents by gavage at a dose of 0.2 mL once a day. Except the blank group， other groups underwent a 6-weeks exhaustive swimming test under negative gravity. At the end of the experiment， blood was collected， and the thymus， spleen， liver， and kidney weights were measured. Serum levels of lactic acid （LD）， blood urea nitrogen （BUN）， creatine kinase （CK）， and malondialdehyde （MDA） were assessed by kits to evaluate fatigue. Hematoxylin-eosin staining was performed to observe pathological changes in the skeletal muscle. Electron microscopy was used to examine the skeletal muscle cell ultrastructure， with a focus on mitochondrial morphological changes. The adenosine triphosphate （ATP） content and activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ in skeletal muscle were determined by kits. The expression levels of key genes and proteins in the PTEN-induced putative kinase 1 （PINK1）-mediated mitochondrial homeostasis pathways in the skeletal muscle were evaluated via Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the model group showed reductions in weight gain rate （P<0.01） and thymus index （P<0.01）， rises in serum levels of LD， BUN， MDA， and CK （P<0.01）， disarrangement of skeletal muscle， broken muscle fibers， inflammatory cell infiltration in muscle fiber gaps， abnormal morphological changes （increased vacuolated mitochondria and disappearance of cristae） of mitochondria in skeletal muscle cells， and decreased mitochondria. In addition， the skeletal muscle in the model group showed reduced content of ATP， weakened activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ （P<0.05）， up-regulated mRNA levels of PINK1， E3 ubiquitin-protein ligase （Parkin）， hairy/enhancer-of-split related with YRPW motif 1 （HEY1）， dynamin-related protein 1 （Drp1）， sequestosome 1 （p62）， and hypoxia-inducible factor 1 alpha （HIF-1α） （P<0.05）， and down-regulated protein level of microtubule-associated protein 1-light chain 3B （LC3B） （P<0.01）. Compared with the model group， Buzhong Yiqitang prolonged the swimming exhaustion time （P<0.01）， increased the weight gain rate （P<0.01） and thymus index （P<0.01）， lowered the serum levels of LD， BUN， MDA， and CK （P<0.05， P<0.01）. The skeletal muscle in the Buzhong Yiqitang groups showed neat arrangement， reduced inflammatory cells， intact mitochondria with dense cristae， and increased mitochondria. In addition， the skeletal muscle in the Buzhong Yiqitang groups showcased increased ATP content， enhanced activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， and Ⅴ （P<0.05， P<0.01）， up-regulated protein levels of PINK1， Parkin， HEY1， LC3B， and Drp1 and mRNA level of HIF-1α （P<0.05， P<0.01）， and down-regulated expression level of p62 （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can prevent and treat exercise-induced fatigue by regulating the mitochondrial homeostasis of skeletal muscle via the HIF-1α/PINK1/Parkin and HIF-1α/HEY1/PINK1 signaling pathways.

ObjectiveThis study aims to investigate the effects of different sizes of seedlings and melatonin treatment on physiological and biochemical indicators and bolting-related gene expression in Angelica sinensis， find substances related to early bolting， and elucidate the inhibitory mechanism of melatonin on bolting. MethodsSpectrophotometry was used to detect the related enzyme activities of A. sinensis leaves. The contents of endogenous hormones and polyamines were detected using ultra-high performance liquid chromatography-tandem mass spectrometry. Real-time polymerase chain reaction （Real-time PCR） was used to detect the expression levels of bolting-related genes. Inter-group differential indicator analysis， orthogonal partial least squares discriminant analysis， and principal component analysis were comprehensively applied to identify factors related to early bolting. ResultsEndogenous jasmonic acid and melatonin were identified as the most important factors affecting early bolting. Secondly， the activity of antioxidant enzymes， abscisic acid content， gibberellin content， and the expression levels of CO3， HD3A， and FD genes had important effects on the bolting process. Compared with small seedlings， exogenous melatonin treatment mainly inhibited early bolting by increasing endogenous melatonin content， reducing gibberellin content， and decreasing the expression levels of SOC1 and FD genes. ConclusionExogenous melatonin can inhibit early bolting in A. sinensis by regulating its physiological， biochemical， and gene expression levels.

Lipid metabolism relates to tumor proliferation, progression, and immune escape. With the rapid development of immunotherapy, the relationship between immunotherapy and lipid metabolism has been constantly explored. On the one hand, immunotherapy can cause dyslipidemia and accelerate the progression of atherosclerosis, which has been neglected by clinicians. On the other hand, lipid metabolism can affect antitumor immunity at multiple levels and potentially influence the efficacy of immunotherapy. Lipid metabolism-regulating drugs also have the potential to synergize with immunotherapy. This review summarizes relevant research evidence to inspire further exploration.

ObjectiveThis study aims to investigate the effects of different sizes of seedlings and melatonin treatment on physiological and biochemical indicators and bolting-related gene expression in Angelica sinensis， find substances related to early bolting， and elucidate the inhibitory mechanism of melatonin on bolting. MethodsSpectrophotometry was used to detect the related enzyme activities of A. sinensis leaves. The contents of endogenous hormones and polyamines were detected using ultra-high performance liquid chromatography-tandem mass spectrometry. Real-time polymerase chain reaction （Real-time PCR） was used to detect the expression levels of bolting-related genes. Inter-group differential indicator analysis， orthogonal partial least squares discriminant analysis， and principal component analysis were comprehensively applied to identify factors related to early bolting. ResultsEndogenous jasmonic acid and melatonin were identified as the most important factors affecting early bolting. Secondly， the activity of antioxidant enzymes， abscisic acid content， gibberellin content， and the expression levels of CO3， HD3A， and FD genes had important effects on the bolting process. Compared with small seedlings， exogenous melatonin treatment mainly inhibited early bolting by increasing endogenous melatonin content， reducing gibberellin content， and decreasing the expression levels of SOC1 and FD genes. ConclusionExogenous melatonin can inhibit early bolting in A. sinensis by regulating its physiological， biochemical， and gene expression levels.