China has the third largest number of tuberculosis cases in the world. As the population ages，there are increasing challenges related to tuberculosis in the elderly. The declined immune function，the endogenous resurgence and exogenous reinfection of tuberculosis，malnutrition and other factors directly affect the prognosis of the disease in elderly patients，among which malnutrition is particularly important. Tuberculosis is a consumptive disease，and the progress of the disease aggravates the occurrence of malnutrition. Malnutrition and tuberculosis are reciprocal causation and react with each other. This article reviews the nutritional status of elderly tuberculosis patients，the significance and methods of nutritional assessment，its current application and limitations，to provide reference of clinical nutritional assessment for elderly tuberculosis patients.

Objective To study the status of diabetic foot and its related factors in Hanzhong area in recent years, and to provide a scientific basis for the prevention and management of diabetic foot complicated by type 2 diabetes. Methods A stratified sampling method was used to select 528 patients with type 2 diabetes among permanent residents in Hanzhong from April 2016 to April 2022. Relevant medical history and laboratory examination data were collected, and the incidence of diabetic foot was calculated. The influence of related factors on the risk of diabetic foot was analyzed by regression model. Results Among 528 subjects in this study, the disease course and body type of T2DM showed that male patients had significantly longer disease, and the proportion of overweight and obesity was higher, P<0.05. The incidence of diabetic foot was 16.29% (86 cases). The proportion of male patients and female patients was 24.66% and 5.93%（χ²=27.516，P<0.05）. The proportion of male patients complicated with diabetic foot was higher than that of female patients (P<0.05). At the same time, the incidence of Wagner Grade I was higher in males than in females (P<0.05). The effects of potential factors on the risk of diabetic foot were discussed by gender. Univariate analysis and multivariate logistic regression analysis indicated that the risk factors of diabetic foot in male T2DM patients included: Increased course of disease, increased age, poor blood glucose control, increased total cholesterol level, increased BMI level and increased platelet to lymphocyte ratio . Potential risk factors in women include increased course of disease, age, poor blood sugar control (increased glycosylated hemoglobin levels) and increased platelet to lymphocyte ratios in all cases（P<0.05）. Conclusion The current prevalence rate of type 2 diabetes patients complicated with diabetes foot in Hanzhong area is 16.29%, which is still high , and the prevalence rate of men is significantly higher than that of women. Older age, long duration of T2DM, poor blood glucose control, increased total cholesterol level, increased blood uric acid level, decreased urine pH value, and increased platelet lymphocyte ratio are potential risk factors for diabetes foot. Male patients should also pay attention to the occurrence of overweight and obesity tendency to reduce the risk of diabetes foot.

Objective To investigate the diagnostic efficacy and clinical value of GNB4 and Riplet gene methylation alone and in combination in the diagnosis of primary liver cancer.Methods A total of 313 patients were selected,including 78 patients with primary liver cancer,41 patients with other digestive system tumors,17 patients with non-digestive system tumors,20 patients with postoperative liver cancer,and 157 patients with benign liver disea-ses.The levels of GNB4 and Riplet gene methylation in plasma were detected using quantitative methylation-specific PCR(qMSP).Serum alpha-fetoprotein(AFP)levels were measured by direct chemiluminescence.Results The sensitivity and specificity of AFP in diagnosis were 51.3％and 94.3％,respectively;the sensitivity and specificity of GNB4 gene methylation in diagnosis were 83.3％and 99.4％,respectively;the sensitivity and specificity of Riplet gene methylation in diagnosis were 73.1％and 99.4％,respectively.The sensitivity and specificity of GNB4 and Riplet gene methylation combined diagnosis were 92.3％and 98.7％,respectively;the sensitivity and specificity of AFP,GNB4 and Riplet gene methylation combined diagnosis were 92.3％and 98.7％,respectively;the sensitivity and specificity of combined diagnosis including age and gender were 93.6％and 97.5％,respective-ly.Conclusion The sensitivity and specificity of AFP in the diagnosis of primary liver cancer are limited,while the methylation levels of GNB4 and Riplet genes are higher,and the sensitivity and specificity of their combined de-tection are higher than those of AFP.The sensitivity and specificity of AFP,GNB4 and Riplet gene methylation combined diagnosis are significantly higher than those of AFP,GNB4 and Riplet gene methylation alone.

Objective:To investigate the surgical method and clinical effect of O-arm navigation mini-open burring for osteoid osteoma.Methods:Eighteen patients with osteoid osteoma were treated with O-arm guided grinding drill from June 2021 to May 2022, including 15 males and 3 females, the age was (18.4 ±10.9) years (range 2 to 44 years), and the course of disease ranged from 1 week to 3 years (mean 14.2 months). The lesions sites included 6 cases of proximal femur, 3 cases of distal femur, 4 cases of proximal tibia, 1 case of distal tibia, 2 cases of proximal fibula and 1 case of distal and proximal humerus. During the operation, the O-arm navigation was used to determine the location of the focus, the muscle and soft tissue was peeled off to the bone surface through a 1-4 cm small incision, the channel retractor was placed, and the burr was registered as a navigation recognition device to gradually remove the bone on the surface of the tumor nest, and the tumor nest was scraped with a curette for pathological examination; according to the navigation image, the focus was enlarged removed with burr and the grinding range was confirmed by the O-arm X-ray machine before the end of the operation. The patients were followed up for 6 to 15 months (mean 9.5 months). CT scans were performed before and after surgery for imaging comparison in order to figure out whether it had residual lesions or recurrence. The visual analogue score (VAS) of pain was used as a parameter for evaluating the clinical efficacy.Results:The operation time of 18 cases was 40-175 min, with an average of 89.3 min. The time required to establish navigation image was 18.0 ±4.1 min (range 13 ~ 22 min). The length of the incision was 2.7±1.1 cm (range 1-4 cm). All patients achieved complete curettage of the lesions, and osteoid osteoma was confirmed by pathology after operation. All the patients could move to the ground 24 hours after operation, and the pain was significantly relieved from 3 to 7 d after operation, and the pain almost disappeared 3 months after operation. The VAS score of 18 cases was 5.33±1.24 before surgery, 2.79±1.32 on the 3rd day, 1.86±1.21 on the 7th day, 0.86±0.93 on the 1st month, 0.33±0.48 on the 3rd month, and 0.09±0.29 on the 6th month after operation, and the difference was statistically significant ( F=58.50, P<0.001). There were no serious complications during and after operation, and the success rate of treatment (no recurrence of symptoms, no residual recurrence of imaging lesions, no serious complications after operation) was 100%. Conclusion:Treatment of osteoid osteoma with mini-open excision using burrs under the navigation of O-arm is a simple, safe, minimally invasive and efficient technique. Intraoperative precise positioning and the use of burr with navigation to remove a larger area than the tumor nest are the keys to successful treatment.

Objective:To explore the risk factors of recurrence after resection of thigh soft tissue malignant tumors and the evaluation of the postoperative lower limb function.Methods:A total of 211 patients who underwent thigh soft tissue malignant tumor resection in the Department of Orthopaedics of the second affiliated Hospital of Medical College of Zhejiang University from May 2011 to May 2021 were retrospectively analyzed, including 117 males and 94 females, aged 53 (43, 65) years. There were 59 cases of atypical/well-differentiated liposarcoma, 30 cases of other types of liposarcoma, 33 cases of malignant fibrous histiocytoma, 19 cases of fibrosarcoma, 12 cases of rhabdomyosarcoma, 12 cases of leiomyosarcoma, 9 cases of synovial sarcoma, and 37 cases of others. The tumor involvement of muscle, bone, blood vessel, nerve tissue and intermuscular compartment, postoperative Musculoskeletal Tumor Society (MSTS) functional score and recurrence were recorded. The relationship between anatomical structure and postoperative recurrence was analyzed by Cox logistic regression to determine risk factors; the cumulative recurrence rate of different compartment groups (medial compartment, anterior compartment, and posterior compartment) were compared; The Box plot was used to compare the postoperative function of patients with resection of different anatomical structures (e.g., vastus lateralis, biceps femoris, femur, etc.).Results:A total of 34 out of 211 patients relapsed, with a recurrence rate of 16.1%. The recurrence time ranged from 2.6 months to 91.6 months after operation, with a median recurrence time of 37.0 (18.2, 52.8) months. Three independent risk factors were found to be associated with recurrence, namely: pathological grade [ HR=3.86, 95% CI(1.75, 8.51)], involvement of vastus intermedius [ HR=3.05, 95% CI(1.53, 6.06)], and involvement of vastus medialis [ HR=3.17, 95% CI(1.56, 6.41)]. The recurrence rate of patients with anterior chamber tumor resection was 35.3%, which was higher than that of patients without tumor resection (16.2%), and the difference was statistically significant ( P=0.020). There was no significant difference in recurrence rate between patients with medial chamber tumor resection and patients without tumor resection ( P>0.05). The recurrence rate of patients with posterior compartment tumor resection was 12.3%, which was lower than that of unresectable patients (37.6%), and the difference was statistically significant ( P=0.002).The postoperative MSTS score of 167 patients averaged 26±3.2 points (9-30 points). After intraoperative resection of part of the femur, vastus intermedius, vastus medialis, and rectus femoris, the patient's function was relatively poor [corresponding median MSTS score: 25 (23, 28), 26 (24 28), 26 (24,28), 26(24, 27)]. Conclusion:The risk factors for local recurrence after resection of thigh soft tissue malignant tumors include: pathological grade of the tumor, and whether the vastus intermedius or vastus medialis is involved. Anterior compartment tumors have a higher recurrence rate after surgery. If the tumor involves the above-mentioned anatomical structures, more attention should be paid to the risk of local recurrence after surgery.

Objective: To investigate the value of combined stool syndecan-2 (SDC2) and tissue factor pathway inhibitor 2 ( TFPI2) gene methylation testing in the early screening of colorectal cancer． Methods : 106 patients with colorectal cancer (colorectal cancer group) ，75 patients with advanced adenoma ( advanced adenoma group) and 35 patients with non-advanced adenoma (non-advanced adenoma group) were selected as study subjects，and 153 patients with other gastrointestinal disorders and 182 patients with negative colonoscopy results during the same period were selected as the control group．The quantitative methylation-specific PCR(qMSP) method was used to detect SDC2 and TFPI2 gene methylation in the stool specimens of all subjects．The sensitivity and specificity of the combined SDC2 and TFPI2 gene methylation assay for the detection of colorectal cancer and adenoma were evaluated using colonoscopy and pathology results as the gold standard. Results : Among 106 patients with colorectal cancer， the sensitivity of combined methylation test was 93. 4% ; among 75 patients with advanced adenoma，the sensitivity of combined methylation test was 62. 7% ; among 35 patients with non-advanced adenoma，the sensitivity of combined methylation test was 34. 3% ; the specificity of the combined SDC2 and TFPI2 gene methylation test for colorectal cancer and adenoma screening was 94. 6%． Conclusion The combined SDC2 and TFPI2 gene methylation test has high sensitivity for colorectal cancer and its early lesions，and it also maintains high specificity.

OBJECTIVE To evalu ate relat ed researches about the cost- benefit of pharmaceutical care in medical institutions with cost- benefit analysis，in order to provide evidence-based basis for related policy decisions and provide methodological reference for the cost- benefit evaluation of pharmaceutical care in the future. METHODS Retrieved from PubMed ，Embase，the Cochrane Library ，CBM，Wanfang database ，VIP and CNKI ，cost-benefit analysis was used to evaluate the researches about the cost-benefit of pharmaceutical care in medical institutions. Two researchers independently screened the research and extracted data according to the “Consolidated Health Economic Evaluation Reporting Standards Checklist ”. The quality of included studies was scored and evaluated systematically. RESULTS A total of 46 studies from 17 countries were included. Most of them came from the United States （21.74％），China（19.57％）and France （8.70％）. Average score of 46 literature was 14.30，of which 1 literature was excellent ，5 literature were good ，25 literature were qualified and 14 literature were unqualified. There were 25 research protocols of prospective study type ；the type of pharmaceutical care involved mostly was pharmaceutical monitoring （60.87％）， followed by prescription review （23.91％），medication reconciliation （8.70％）and outpatient pharmacy （6.52％）were less. The median cost-benefit ratio of pharmaceutical care was 5.05 （3.08，11.28）. CONCLUSIONS Pharmaceutical care shows good economic value ，and pharmacists have played an important role in saving medical resources ，but the design level and report quality of the existing studies need to be improved.

OBJECTIVE： To investigate the protective effect and its mechanism of thymoquinone （TQ） on myocardial fibrosis （MF） induced by lipopolysaccharide in rats. METHODS： Totally 40 male Wistar rats were randomly divided into control group， model group， TQ low-dose and high-dose groups [5， 10 mg/（kg?d）]， with 10 rats in each group. Except that control group was given constant volume of normal saline intraperitoneally， other groups were given LPS intraperitoneally to induce MF model， once a day， for consecutive 3 weeks. Since the first day of modeling， administration group was given relevant medicine intraperitoneally， once a day， for consecutive 3 weeks. After last medication， ELISA method was used to detect the contents of serum inflammation factors （IL-1β， IL-6， TNF-α） in rats. Cardiac mass parameters （HW/BM， LVW/BW） were weighed and calculated. HE staining was used to observe the histopathological changes of myocardial tissue. The contents or activities of oxidative stress indicators （MDA， SOD） and myocardial collagen indexes （HYP， Col-Ⅰ， Col-Ⅲ） were detected by chemical analysis， xanthine oxidase method or ELISA. mRNA expression of regulation genes （Col-Ⅰ， Col-Ⅲ， MMP-3， MMP-9， TGF-β1 and Smad3） related to myocardial fibrosis were determined by real-time fluorescence quantitative PCR. RESULTS： Compared with control group， there were swollen myocardial cells， disordered nuclei of different sizes and visible fiber hyperplasia in model group； the levels of serum inflammatory factors and LVW/BW， cardiac contents of MDA， HYP， Col-Ⅰand Col-Ⅲ， mRNA expression of Col-Ⅲ， TGF-β1 and Smad3 in model group were increased significantly （P＜0.05）， while SOD activity was decreased significantly （P＜0.05）. Compared with model group， the degree of myocardial fibrosis was improved in TQ groups to different extents； serum content of IL-1β and the contents of MDA， HYP and Col-Ⅰ in cardiac tissue in TQ low-dose group， serum contents of IL-1β， IL-6 and TNF-α， LVW/BW and the contents of MDA， HYP， Col-Ⅰ and Col-Ⅲ in cardiac tissue of TQ high-dose group as well as mRNA expression of Col-Ⅰ， Col -Ⅲ， TGF-β1 in TQ groups were decreased significantly （P＜0.05）. The activities of SOD in cardiac tissue were increased significantly in TQ groups （P＜0.05）. There was no statistical significance in other indexes among groups （P＞0.05）. CONCLUSIONS： TQ can protect against MF model rats to certain extent， the mechanism of which may be associated with the inhibition of inflammation reaction and oxidant stress reaction， and down-regulation of mRNA expression of Col-Ⅰ， Col-Ⅲ and TGF-β1.

OBJECTIVE: To explore the expression, localization and regulatory effect on mitochondrial calcium signaling of Rictor in embryonic stem cell-derived cardiomyocytes (ESC-CMs). METHODS: Classical embryonic stem cell cardiomyogenesis model was used for differentiation of mouse embryonic stem cells into cardiomyocytes. The location of Rictor in ESC-CMs was investigated by immunofluorescence and Western blot. The expression of Rictor in mouse embryonic stem cells was interfered with lentiviral technology, then the superposition of mitochondria and endoplasmic reticulum (ER) in ESC-CMs was detected with immunofluorescence method; the cellular ultrastructure of ESC-CMs was observed by transmission electron microscope; the mitochondrial calcium transients of ESC-CMs was detected by living cell workstation;immunoprecipitation was used to detect the interaction between 1,5,5-trisphosphate receptor (IP3 receptor, IP3R), glucose-regulated protein 75 (Grp75) and voltage-dependent anion channel 1 (VDAC1) in mitochondrial outer membrane; the expression of mitochondrial fusion protein (mitonusin-2, Mfn2) was detected by Western blot. RESULTS: Rictor was mainly localized in the endoplasmic reticulum and mitochondrial-endoplasmic reticulum membrane (MAM) in ESC-CMs. Immunofluorescence results showed that Rictor was highly overlapped with ER and mitochondria in ESC-CMs. After mitochondrial and ER were labeled with Mito-Tracker Red and ER-Tracker Green, it was demonstrated that the mitochondria of the myocardial cells in the Rictor group were scattered, and the superimposition rate of mitochondria and ER was lower than that of the negative control group (<0.01). The MAM structures were decreased in ESC-CMs after knockdown of Rictor. The results of the living cell workstation showed that the amplitude of mitochondrial calcium transients by ATP stimulation in ESC-CMs was decreased after knockdown of Rictor (<0.01). The results of co-immunoprecipitation showed that the interaction between IP3R, Grp75 and VDAC1 in the MAM structure of the cardiomyocytes in the Rictor group was significantly attenuated (<0.01); the results of Western blot showed that the expression of Mfn2 protein was significantly decreased (<0.01). CONCLUSIONS Using lentiviral technology to interfere Rictor expression in mouse embryonic stem cells, the release of calcium from the endoplasmic reticulum to mitochondria in ESC-CMs decreases, which may be affected by reducing the interaction of IP3R, Grp75, VDAC1 and decreasing the expression of Mfn2, leading to the damage of MAM structure.
Animals ; Calcium Signaling ; genetics ; Gene Expression Regulation ; genetics ; Gene Knockdown Techniques ; Mice ; Mitochondria ; physiology ; Mouse Embryonic Stem Cells ; Myocytes, Cardiac ; physiology ; Protein Transport ; Rapamycin-Insensitive Companion of mTOR Protein ; genetics ; metabolism

Objective To investigate if the positive postnatal environment could modify the schizo-phrenia-related behaviors caused by early maternal immune activation,and the interaction of this two pre-and postnatal factors.Methods The pregnant mice were randomly divided into experimental and control groups.The experimental groups were injected with polynosinic-polycytidylic acid(Poly I : C)(5mg/kg),via intra-venous route,at gestational day 9.The control groups were injected with the same volume of normal saline (NS)at the same gestational day.All offspring were housed in groups of littermates until postnatal day (PND)21 when they were weaned.Between PND22-PND60,offspring were divided into dull or enriched en-vironment(DE or EE)groups by sex and treatment.Different toys were put into the cages of enriched envi-ronment group every week,such as running wheels,climbing materials,swings and rollers.The dull environ-ment(DE)groups were kept the normal housing environment only with sawdust.At PND60,behavioral tests were conducted,such as prepulse inhibition(PPI),open field test,novel object/location recognition,social interaction test,as well as water maze test,were conducted to evaluate the performance of all offspring.After behavioral tests,all offspring were killed and the hippocampus were dissected.The western blot was used to analyze the expression of myelin basic protein in the hippocampus.Results (1)The percentage of PPI with early maternal immune activation of Poly I : C were significantly reduced when compared with control groups (female offspring:F=28.12,P<0.001;male offspring:F=14.76,P<0.01),suggesting the schizophrenia-like behavioral deficit in the offspring induced by early prenatal Poly I : C challenge.(2)In open field test,early maternal immune activation increased the moved distance and speed of the offspring compared with the con-trol groups(female offspring:distances,F=5.10,P<0.05,speed:F=5.19,P<0.05;male offspring:distances:F=6.76,P<0.05,velocity:F=6.85,P<0.05,vs each corresponding control).(3)Enriched environment in-creased the social interaction time of offspring with strange mouse in the social interaction test(female off-spring:EE group(101.30±6.83)s,DE group(76.50±5.59)s,F=9.41,P<0.01;male offspring:EE group(98. 52±6.82)s,DE group(75.82±3.95)s,F=7.95,P<0.01).(4)Enriched environment decreased the time for offspring to find the platform in water maze test(P<0.05).(5)The expression of myelin basic protein in hip-pocampus in offspring which received early maternal immune activation by Poly I : C was lower than that in the control groups(P<0.05).Conclusion The postnatal enriched environment increased the social interac-tion and the learning abilities of the offspring with early maternal immune activation by Poly I : C in water maze,and even more improved the perseveration behavior of the offspring induced by the early maternal im-mune activation.