BACKGROUND:Iron overload refers to excessive accumulation of iron in the body,which can cause pathological changes in various tissues.At present,the molecular mechanism and potential gene targets related to iron overload in osteoarthritis still need to be further studied and explored. OBJECTIVE:To analyze the key genes of iron overload in osteoarthritis by means of bioinformatics and verify them in animal experiments,so as to provide a new idea for preventing and treating osteoarthritis from the perspective of iron overload. METHODS:GEO database and GeneCards database were used to screen out genes associated with osteoarthritis and genes associated with iron overload.Then,the intersection of the two was taken to obtain a collection of genes commonly associated with osteoarthritis and iron overload.GO and KEGG enrichment analyses were used to screen the functions and pathways of these genes.To further investigate the interactions between these genes,a protein-protein interaction network was constructed and five computational methods of Cytoscape software were utilized to identify the Hub genes for iron overload in osteoarthritis.Finally,12 male Sprague-Dawley rats were divided into osteoarthritis group and normal group,with 6 rats in each group.A knee osteoarthritis model was established by the modified Hulth method in the osteoarthritis group.The expression of Hub genes in the knee joint of rats in each group was detected by PCR. RESULTS AND CONCLUSION:(1)A total of 51 genes associated with iron overload were identified in osteoarthritis.GO enrichment analysis showed that these genes were mainly involved in cytokine receptor binding,chemokine receptor binding,cytokine activity,growth factor receptor binding and oligosaccharide binding.(2)KEGG enrichment analysis showed that genes associated with iron overload in osteoarthritis was mainly involved in tumor necrosis factor signaling pathway and lipid and atherosclerosis signaling pathway.(3)The protein-protein interaction network was constructed,and five Hub genes of iron overload,intercellular cell adhesion molecule-1,tumor necrosis factor superfamily member 11,myelocytomatosis oncogene,janus kinase 2,and interleukin 6,were obtained by further analysis.Animal experiments verified that there were significant differences in the expression of the above Hub genes in the rat knee joint between the control group and the experimental group(P<0.05).(4)All these findings show that intercellular cell adhesion molecule-1,tumor necrosis factor superfamily member 11,myelocytomatosis oncogene,janus kinase 2,and interleukin 6 can be used as the Hub genes of iron overload in osteoarthritis,which are expected to become new targets for the prevention and treatment of osteoarthritis.

Objective To analyze the deep venous thrombosis(DVT)after plasma infusion in a patient with congenital dysfibrinogene-mia(CD),and explore the relationship between the CD and DVT.Methods The clinical data were collected and the pedigree was investigated(3 subjects of 2 generations in total).The relevant indexes of coagulation factors of the patient and her family members were detected.The genomic DNA of peripheral blood was extracted for PCR amplification.All the exons,flanking sequences,5'and 3'untranslated regions of FGA,FGB and FGG genes of fibrinogen(Fg)of the patient were analyzed by direct sequencing.The corre-sponding mutation site was subjected to sequence in the other members of this family.The PyMol software was used to construct the pro-tein model before and after gene mutation.Results The patient was admitted to hospital for hysteromyomectomy.DVT appeared in 3 days after surgery.The prothrombin time(PT),thrombin time(TT),Fg activity(Fg∶C)and Fg antigen(Fg∶Ag)of the patient was 14.9 s,33.3 s,0.94 g/L and 2.10 g/L,respectively.The above four indicators in her mother were 14.7 s,32.8 s,0.97 g/L and 2.35 g/L,respectively.Gene sequencing revealed that both the patient and her mother had a heterozygous missense mutation c.2185G＞A(p.Glu729Lys)in exon 6 of the FGA gene.The protein model analysis demonstrated that p.Glu729Lys mutation changed the amino acid side chain and reduced the number of hydrogen bonds originally formed with Arg854.Conclusion A heterozygous missense mutation c.2185G＞A(NM_000508)in exon 6 of the FGA gene should be responsible for the low fibrinogen level in this pedigree,which might be the main reason for DVT after plasma infusion in this patient.

Liver transplantation is the optimal treatment for end-stage liver disease and hepatocellular carcinoma, which can significantly improve clinical prognosis and quality of life of patients. However, multiple challenges, such as rejection, immune tolerance, shortage of donor liver, preservation of donor liver, ischemia-reperfusion injury and postoperative complications, etc., limit the efficacy of liver transplantation in clinical practice. Research teams in China have made significant contributions to the basic research related to liver transplantation by making continuous efforts and combining the development of emerging technologies, interdisciplinary integration and other emerging fields. In this article, the frontier progress in the basic research of liver transplantation in 2023 was reviewed, highlighting the progress made by Chinese research teams in the basic research of liver transplantation, aiming to provide reference for promoting the integration of Chinese characteristics into the research of liver transplantation, accelerate the integration of Chinese liver transplantation research with international community, and promote further advancement of liver transplantation in China.

Objective To investigate and analyze a group occupational acute dimethylacetamide (DMA) poisoning incident occurred during the post-fire cleaning operation in a spandex manufacturing enterprise. Methods This study focused on the involved enterprise, employing units, poisoning patients, and workers with similar occupational exposure history from a group occupational acute chemical poisoning incident in Guangdong Province in 2023. Occupational health on-site investigation data, clinical records of poisoned patients, and occupational disease diagnostic data were collected to determine the cause of the poisoning. Results The incident occurred at a spandex manufacturing enterprise during the cleaning of polymerization reaction vessels after a fire, resulting in poisoning of six cleaning workers. The clinical symptoms of patients included varying degrees of liver function abnormalities and skin damage. All six patients wore long-tube air-supplied full-face masks during work. The patients were in a confined work space with poor ventilation, and worked more than 8 hours per day. Patients felt unwell after 5-13 days of work. Post-incident investigation revealed that the DMA exposure concentration of short term near the reaction vessels was 36.06 mg/m³. DMA accounted 13.74% to 30.09% of the volatile organic compounds in the raw and auxiliary materials and waste in the vessel. N-methylacetamide was detected in the urine of these six patients, with levels up to 1 639.78 mg/g creatinine, exceeding the occupational exposure limit (20.00 mg/g creatinine). All six patients were diagnosed as occupational acute DMA poisoning. Conclusion Occupational acute DMA poisoning mainly causes liver damage, has a latent onset, and poses a risk of group occurrence. The main causes of group poisoning are confined work space, inadequate management, insufficient protective measures, and excessive working hours.

ObjectiveTo construct a quantitative prediction model of three indicators（moisture absorption rate， film thickness and coating weight gain） during the coating process of Vitamin C Yinqiao tablets（VCYT） by near-infrared spectroscopy（NIRS）， and to realize the endpoint judgment. MethodReal-time NIRS data of 4 batches of VCYT during the coating process were collected by diffuse reflection method. The coating method employed was the rolling coating method， and the samples were obtained at the spray stage from the coater's sampling port every 10 minutes， and 57 batches of samples（about 1 800 tablets） were collected at various coating times， the tablets were embedded in molten paraffin， cut longitudinally， and observed by stereomicroscope. The film thickness， with a target value of 38 μm， was then measured using Motic Images Advanced 3.2 software. Furthermore， the mositure absorption rate of samples， aiming for a target value of 3%， was determined in accordance with guiding principles for drug hygroscopicity testing in the 2020 edition of Chinese Pharmacopoeia， and 3 samples were randomly selected from each batch（10 tablets per batch）， and the coating weight gain was calculated（target value of 4%）. Partial least squares regression（PLSR） was used to construct a quantitative model of the 3 coating indicators， and the predicted values of the coating indicators were smoothed using the moving average method and used to determine the coating endpoints. ResultThe prediction determination coefficients（R_p²） for moisture absorption rate， film thickness and coating weight gain were 0.933 4， 0.932 6 and 0.965 9， the root mean square errors of prediction（RMSEP） were 0.163 5%， 1.870 9 μm and 0.240 3%， the relative percent deviations（RPD） were 3.711 0， 2.760 7 and 5.415 8， respectively. The results of the external validation set demonstrated that the real-time predicted values obtained by the models exhibited the same trend as the measured values， and the coating endpoint could be accurately predicted（with a prediction error of less than 7.32 min and a relative error of less than 5.63%）. ConclusionThe established NIRS model exhibits excellent predictive performance and can be used for quality control of VCYT during the coating process.

Objective:To investigate the role of m.4435A>G and YARS2 c.572G>T(p.G191V)mutations in the development of essential hypertension.Methods:A hypertensive patient with m.4435A>G and YARS2 p.G191V mutations was identified from previously collected mitochondrial genome and exon sequencing data.Clinical data were collected,and a molecular genetic study was conducted in the proband and his family members.Peripheral venous blood was collected,and immortalized lymphocyte lines constructed.The mitochondrial transfer RNA(tRNA),mitochondrial protein,adenosine triphosphate(ATP),mitochondrial membrane potential(MMP),and reactive oxygen species(ROS)in the constructed lymphocyte cell lines were measured.Results:Mitochondrial genome sequencing showed that all maternal members carried a highly conserved m.4435A>G mutation.The m.4435A>G mutation might affect the secondary structure and folding free energy of mitochondrial tRNA and change its stability,which may influence the anticodon ring structure.Compared with the control group,the cell lines carrying m.4435A>G and YARS2 p.G191V mutations had decreased mitochondrial tRNA homeostasis,mitochondrial protein expression,ATP production and MMP levels,as well as increased ROS levels(all P<0.05).Conclusion:The YARS2 p.G191V mutation aggravates the changes in mitochondrial translation and mitochondrial function caused by m.4435A>G through affecting the steady-state level of mitochondrial tRNA and further leads to cell dysfunction,indicating that YARS2 p.G191V and m.4435A>G mutations have a synergistic effect in this family and jointly participate in the occurrence and development of essential hypertension.

Objective:To observe Leber's hereditary optic neuropathy (LHON) microperimetry features, discuss its significance in diagnosis and treatment of LHON assessment.Methods:A retrospective clinical study. A total of 13 LHON patients (25 eyes) diagnosed in Department of Ophthalmology of the First Affiliated Hospital of Army Medical University from May 2015 to May 2020 (disease group) were included in the study, including 9 males (18 eyes) and 4 females (7 eyes), and beginning with the age of 15.0 (10.0, 57.0). Ten healthy volunteers (19 eyes) were selected as the normal group, including 7 males (13 eyes) and 3 females (6 eyes), aged 22.0 (6.0, 46.0) years at the first diagnosis. According to the course is divided into: asymptomatic group (carriers), subacute (<6 months), the dynamic group (6-12 months), chronic group (>12 months). There were 7, 6, 5 and 7 eyes, respectively. All eyes underwent best corrected visual acuity (BCVA) and microperimetry. BCVA test was performed using the international standard visual acuity chart, which was statistically converted to the logarithm of the minimum Angle of resolution (logMAR) visual acuity. MP-3 microperimetry was used to perform microperimetry, and the mean sensitivity (MS) values of five regions were recorded: center, superior, temporal, inferior, and nasal. Mann-Whitney U test was used for comparison between two groups, and Kruskal-Wallis H test was used for comparison between multiple groups. Results:Compared with the normal group, MS in the center, superior, temporal, inferior and nasal of the diseased group decreased, and the differences were statistically significant ( Z=-5.629, -4.906, -5.630, -5.631, -5.227; P<0.05). There were significant differences in different regions of MS between different course groups ( H=12.296, 11.583, 10.110, 12.994, 8.663; P<0.05). There were significant differences in logMAR BCVA and central MS between asymptomatic group and subacute group ( P=0.040, 0.007). There were significant differences in temporal, inferior and superior MS between subacute group and dynamic group ( P=0.026, 0.017, 0.018). Dynamic and chronic group, MS above the difference was statistically significant ( P=0.031). Idebenone treatment significantly improved visual field defects in 4 of 23 eyes. Conclusions:In the early stage of LHON, the central visual field defect gradually progresses to the temporal, inferior and superior areas, and the temporal and inferior areas are more severe. Visual field defects reached a stable level at 6-12 months. MP-3 can assist in early diagnosis of LHON, and provide reliable basis for efficacy evaluation.

ObjectiveThe hygroscopic properties of Mume Flos decoction pieces were studied from the perspectives of macroscopic［water activity（A_w）］ and microscopic（water molecular mobility）， which provided a theoretical basis for the determination of the safe storage moisture content. MethodAdsorption isotherm of Mume Flos decoction pieces was obtained by static weighing method， and seven common hygroscopic models were fitted and estimated. The best model was selected according to the principle that determination coefficient（R²） was closer to 1， residual sum of squares（RSS） was closer to 0 and Akaike information criterion（AIC） was smaller. According to the optimal model， the absolute and relative safe moisture contents of Mume Flos decoction pieces at 25， 35， 45 ℃ was calculated. Low-field nuclear magnetic resonance（LF-NMR） was used to measure the water molecular mobility in the hygroscopic process of Mume Flos decoction pieces. ResultThe best model to describe the adsorption isotherm of Mume Flos decoction pieces was the Peleg model. According to the model expression， the absolute safe moisture contents of Mume Flos decoction pieces at 25， 35， 45 ℃ were 9.59%， 7.96% and 7.68%， and the relative safe moisture contents were 13.05%， 11.99%， 11.77%， respectively. Mume Flos decoction pieces all contained two water states during the process of hygroscopic absorption at different temperatures， namely bound water T₂₁ and free water T₂₂. During the process of hygroscopic absorption， bound water had the largest increase in peak area. The sum of peak areas of the bound water and free water had a good linear relationship with the moisture contents， and the R² were 0.959 9， 0.911 8 and 0.974 7 at 25， 35， 45 ℃， respectively. When A_w<0.57， T₂₁ did not change， and the water molecular mobility remained unchanged. When A_w>0.57， T₂₁ showed an increasing trend， and the water molecular mobility increased. The moisture contents of Mume Flos decoction pieces were 8.44%， 6.81% and 6.25% when the water molecular mobility increased at 25， 35， 45 ℃， respectively. ConclusionCombined with the theory of water activity and water molecular mobility， 6.25% is recommended as the safe storage moisture content of Mume Flos decoction pieces， this study can provide reference for determining the safe storage moisture content of other decoction pieces.

Objective:To explore the expression level and clinicopathological characteristics of 14-3-3θ protein in distal cholangiocarcinoma tissues, and further analyze the long-term prognosis of patients with different expression levels.Methods:A retrospective cohort study was conducted to collect and analyze the clinical data of 135 patients with distal cholangiocarcinoma who underwent surgical resection at the Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 2015 to December 2021, including 86 males and 49 females.(65.1±10.1) years old. Immunohistochemistry was used to detect the expression level of 14-3-3θ protein in cholangiocarcinoma tissue. The postoperative pathological sections of patients were evaluated based on the immune response score(IRS). The optimal cutoff value was determined through the receiver operating characteristic(ROC) curve was 3.5. Currently, the area under the curve was 0.741, the sensitivity was 73.5%, and the specificity was 71.3%. The patients were divided into two groups: IRS<4 was the 14-3-3θ low expression group( n=81), IRS≥4 was the 14-3-3θ high expression group( n=54). After surgery, the patient′s survival status was followed up through a combination of outpatient review and telephone follow-up. Normally distributed measurement data were expressed as mean ± standard deviation( ± s), and comparisons between groups were made using the t test; non-normally distributed measurement data were expressed as M( Q1, Q3), and comparisons between groups were made using the rank sum test. The chi-square test was used to compare enumeration data between groups. Results:The preoperative CA19-9 and lymph node metastasis in the 14-3-3θ low expression group were 44.3(20.8, 132.2) U/mL and 28 cases respectively. The preoperative CA19-9 and lymph node metastasis in the 14-3-3θ high expression group were 82.3(43.4, 396.9) U/mL and 32 cases respectively. The difference between the two groups was statistically significant( P<0.05). All patients had regular postoperative telephone calls or return to the hospital for follow-up. The median postoperative survival time of the 14-3-3θ low-expression group was 36 months. The 1-, 2-, and 3-year survival rates after surgery were 88.9%, 66.5%, and 66.5%, respectively. 49.4%, the median survival time after surgery in the 14-3-3θ high expression group was 13 months, and the 1, 2, and 3-year survival rates after surgery were 53.7%, 23.3%, and 13.3% respectively. The difference between the two groups was statistically significant. significance( P<0.01). Cox proportional hazard model performed multivariate analysis, CA19-9>37 U/mL ( RR=1.970, 95% CI: 1.186-3.272, P=0.009), lymph node metastasis( RR=1.681, 95% CI: 1.035-2.729, P=0.036) and 14-3-3θ staining intensity≥4 ( RR=2.438, 95% CI: 1.546-3.845, P<0.001) have worse long-term prognosis. Conclusions:The expression level of 14-3-3θ protein is related to CA19-9 and lymph node metastasis in distal cholangiocarcinoma. A high expression of 14-3-3θ protein indicates poor long-term prognosis in patients with extrahepatic cholangiocarcinoma.

Objective:To investigate the clinical efficacy of induced membrane technique in the staged treatment of adult chronic hematogenous osteomyelitis (CHOM) of long bone.Methods:The clinical data were retrospectively analyzed of the 22 adult patients with CHOM of long bone who had been admitted to the 920th Hospital, Joint Logistics Support Force of PLA from January 2016 to December 2019. There were 18 males and 4 females, aged from 16 to 56 years (average, 31.81 years). Their disease duration ranged from 0.6 to 42.0 years, averaging 18.4 years. By the Cierny-Mader anatomical classification, 4 cases were type Ⅰ, 6 cases Type Ⅲ, and 12 cases type Ⅳ. In the first stage, the bone defects were filled with antibiotic bone cement after thorough debridement. In the second stage when the infection had been controlled, the bone defects were repaired with bone grafts after removal of the bone cement. Bone healing time and complications were followed up. The treatment effects were evaluated by comparisons of the infection control indexes [including clinical manifestations like local redness, swelling, pus, and pain, and blood white blood cell count, C-Reactive protein (CRP), and erythrocyte sedimentation rate (ESR) as well] before the primary surgery, before the secondary surgery and at the last follow-up.Results:The volumes of the bone defects after stage-one debridement ranged from 54 cm 3 to 176 cm 3 (mean, 90.9 cm 3). All patients were followed up for 20 to 51 months (mean, 30.1 months) after surgery. All bone defects healed after 4 to 11 months (mean, 6.6 months). Postoperatively, infection developed at the bone extraction site of the posterior superior iliac spine in 3 cases and pain was observed at the donor site in one case, but the conditions were relieved after symptomatic treatment. Fracture and plate breakage occurred at the bone defect site in one case who had fallen down 7 months after operation, but responded to reoperation. The last follow-up revealed such symptoms as redness, swelling and pus discharge in none of the patients. The white blood cell count [(5.70 ± 1.57) × 10 9/L and (5.65 ± 1.58) × 10 9/L], CRP [(7.56 ± 2.57) mg/L and (7.25 ± 3.83) mg/L] and ESR [(9.64 ± 2.90) mm/h and (10.55 ± 5.23) mm/h] before the secondary surgery and at the last follow-up were significantly lower than those before the primary surgery [(8.24 ± 2.18) × 10 9/L, (49.54 ± 19.56) mg/L, and (42.68 ± 13.77) mm/h] (all P < 0.05). However, there were no significant differences between the indexes before the secondary surgery and at the last follow-up ( P > 0.05). Conclusion:In the staged treatment of adult CHOM of long bone, the induced membrane technique can effectively control infection, achieve repair of bone defects, and reduce complications.