Case 1: A 19-day-old male infant presented with poor feeding and decreased activity for 2 weeks, worsening with poor responsiveness for 3 days. At 5 days old, he developed poor feeding and poor responsiveness, was hospitalized, and was found to have elevated blood ammonia and thrombocytopenia. Whole-genome genetic analysis revealed a pathogenic homozygous mutation in the PCCA gene, NM-000282.4: c.1834-1835del (p.Arg612AspfsTer44), leading to a diagnosis of propionic acidemia. Case 2: A 4-day-old male infant presented with poor responsiveness and feeding difficulties since birth, with elevated blood ammonia for 1 day. He showed weak sucking and deteriorating responsiveness, with blood ammonia >200 µmol/L. Genetic testing identified two heterozygous mutations in the MMUT gene: NM_000255.4: c.1677-1G>A and NM_000255.4: ex.5del, confirming methylmalonic acidemia. Case 3: A 20-day-old male infant presented with poor feeding for 15 days and skin petechiae for 8 days. He developed feeding difficulties at 5 days old and lower limb petechiae at 12 days old, with blood ammonia measured at 551.6 µmol/L. Genetic analysis found two heterozygous mutations in the PCCA gene: NM_000282.4: c.1118T>A (p.Met373Lys) and NM_000282.4: ex.16-18del, confirming propionic acidemia. In the first two cases, continuous hemodiafiltration was performed for 30 hours and 20 hours, respectively, before administering carglumic acid. In the third case, carglumic acid was administered orally without continuous hemodiafiltration, resulting in a decrease in blood ammonia from 551.6 µmol/L to 72.0 µmol/L within 6 hours, with a reduction rate of approximately 20-25 µmol/(kg·h), similar to the first two cases. Carglumic acid was effective in all three cases, suggesting it may help optimize future treatment protocols for organic acidemia.
Humans ; Male ; Infant, Newborn ; Propionic Acidemia/drug therapy* ; Amino Acid Metabolism, Inborn Errors/genetics* ; Mutation ; Methylmalonyl-CoA Decarboxylase/genetics* ; Citrates/administration & dosage* ; Carbon-Carbon Ligases/genetics* ; Glutamates

Objective To investigate the efficacy and safety of intensity-modulated radiation therapy combined with camrelizumab in the treatment of advanced hepatocellular carcinoma(HCC).Methods A total of 84 patients with advanced HCC admitted to our hospital from January to December 2020 were selected as the study objects,and were randomly divided into the observation group and the control group,with 42 cases in each group.Patients in the observation group received intensity-modulated radiation therapy combined with carrelli-zumab,and patients in the control group received intensity-modulated radiation therapy.The short-term efficacy,immune function and long-term survival rate of patietns in the two groups were compared,and the incidence of adverse reactions was recorded.Results The total effec-tive rates of the observation group 1 month and 3 months after treatment were significantly higher than those of the control group(P<0.05).The levels of CD3+,CD4+ and CD4+/CD8+ 1 month and 3 months after treatment were all increased in the two groups,while the levels of CD8+ in both two groups were decreased(P<0.05),and the levels of CD3+,CD4+ and CD4+/CD8+ in the observation group were higher than those in the control group(P<0.05),and the levels of CD8+ in the observation group were lower than those in the control group(P<0.05).The median survival time of patients in the observation group was significantly longer than that of patients in the control group(P<0.05).The incidence of cutaneous capillary hyperplasia in the observation group was higher than that in the control group(P<0.001),and there was no significant difference in the incidence of other adverse reactions between the two groups(P>0.05),and all of adverse reactions were grades 1 to 2.Conclusion Intensity-modulated radiation therapy combined with camrelizumab has a good effect on HCC,it can improve the immune function of the body,and control the development of the disease,with good safety.

Objective:To investigate the diagnostic value of serum ferritin in intestinal failure-associated liver disease. Methods:Clinical data of adult patients with short bowel syndrome admitted to the Department of General Surgery of Jinling Hospital affiliated to Nanjing University from January 2019 to December 2022 were retrospectively analyzed to determine the correlation between serum ferritin and liver enzyme profiles by linear regression,to screen the potential risk factors of liver injury by multifactorial Logistic regression analysis,and to establish a prediction model for liver fibrosis. The area under the curve was also calculated to assess the accuracy of the model. Results:A total of 106 patients with short bowel syndrome were included,of whom 55 (51.9％) had elevated serum ferritin (SF). Linear regression analysis showed a positive correlation between serum ferritin and ALT (r=0.427,P<0.001),ALP (r=0.365,P<0.001),and γ-GT (r=0.423,P<0.001),and one-way Logistic regression analysis showed that the higher the level of serum ferritin,the more pronounced the difference was (SF>ULN) The one-way logistic regression analysis showed that the higher the serum ferritin level,the more significant the difference was[SF>ULN (upper limit of normal value of serum ferritin),P=0.033;SF>1.5×ULN,P=0.018;SF>2.5×ULN,P=0.006]. Multifactorial logistic regression analysis showed that PN dependence (OR=3.366,P=0.017) and serum ferritin>2.5 ULN (OR=3.292,P=0.014)were independent risk factors for intestinal failure-associated liver disease-liver fibrosis,and the receiver operating curve (ROC) of the subjects showed area under the curve of 74.8％,95％ CI:0.652～0.844. Conclusion:Serum ferritin can be used as a reliable clinical biomarker to help identify intestinal failure-associated liver disease.

OBJECTIVE: To explore weight-bearing stability of Pilon fracture fixed by external fixator. METHODS: Six ankle bone models (right side) and 4 pairs (8 ankle cadaver specimens) were selected. Pilon fracture model was prepared by using the preset osteotomy line based on Ruedi Allgower Pilon fracture type. Pilon fracture model was built by using a minimally invasive osteotomy. After ankle bone model and cadaver specimen model were fixed with external fixator, axial load was carried out on mechanical loading machine. After ankle bone model and cadaver specimen model were fixed with external fixator, axial load was carried out on mechanical loading machine. Axial loads of 150, 300 and 450 N were applied to ankle bone model, and displacements of fibula fracture blocks, lateral tibia fracture blocks and medial tibia fracture blocks in three-dimensional space (X, Y and Z axes) were recorded by dynamic capture instrument. Axial loads of 300, 600 and 900 N were applied to ankle cadaver model fixed by external fixator. X-ray films of Pilon fracture cadaver model fixed by external fixator under different loading conditions were taken. The anterior tibial angle, tibial malleolar point angle, talus shift value, talus tilt angle, lateral malleolar shift value, lateral malleolar shift value, medial malleolar separation shift value and articular surface step displacement value were measured under different loads by digimizer software. RESULTS: After 150, 300 and 450 N axial loads were applied to Pilon fracture models fixed by external fixator, no loosening or fracture of external fixator was observed, and no loosening, fracture or irreversible plastic deformation of Kirschner needle were observed. The displacement values of fibular fracture pieces on X-axis(around) were 0.032 (-0.022, 0.269), 0.061 (-0.002, 0.427), 0.212(-0.016, 1.223) mm, and the displacement values on Y-axis(above and below) were 0.002(-0.031, 0.103), 0.051(-1.133, 0.376), 0.128 (-1.394, 0.516) mm, and displacement values on Z-axis (front and rear) were -0.003 (-0.130, 0.171), 0.137 (-0.076, 0.433), 0.030(-0.487, 0.478) mm;the displacement values of lateral tibial fractures on X-axis were 0.000(-0.108, 0.027), 0.083(-0.364, 0.050), -0.121(-0.289, 0.165) mm, and displacement values on Y-axis were -0.009(-0.200, 0.025), -0.179(-0.710, 0.084), -0.257(-0.799, 0.027) mm, and displacement values on Z-axis were 0.112(-0.024, 0.256), 0.157(-0.068, 0.293), -0.210(-0.035, 0.430) mm;the displacement values of medial tibial fracture block on X-axis were -0.010(-0.060, 0.013), -0.165(-0.289, 0.056), -0.181(-0.395, 0.013) mm, and the displacement values on Y-axis were -0.036(-0.156, 0.007), -0.104(-0.269, 0.178), -0.245(-0.380, -0.011) mm, and displacement values on Z-axis were -0.005(-0.372, 0.189), -0.012 (-1.774, 0.380), 0.200 (-1.963, -0.540) mm. After 300, 600 and 900 N axial loads were applied to Pilon fracture cadaverous models fixed with external fixators, there were no significant difference in anterior tibial angles, angles of malleolar points of tibia, oblique angles of talus, fracture steps, shift values of talus, lateral shift values of lateral malleolus, lateral shift values of medial malleolus, lateral shift values of medial malleolus between under different loading conditions and those without loading (P>0.05). No loosening or fracture of external fixator as a whole, loosening, fracture or irreversible deformation of Kirschner needle at the local fixed fracture end occurred. CONCLUSION The early weight-bearing external fixator could maintain stability of fracture end and ankle joint, and the maximum weight is not more than 300 N. In clinical practical application, material characteristics of the implant and type of fracture should be selected.
Humans ; Weight-Bearing ; Biomechanical Phenomena ; External Fixators ; Tibial Fractures/physiopathology* ; Fracture Fixation/instrumentation* ; Male

AIM To analyze saponins from Panacis Quinquefolii Radix of different regions(Jilin,Liaoning,Heilongjiang,Shandong)based on UHPLC-Q-Orbitrap/MS technology.METHODS Panacis Quinquefolii Radix had its saponins qualitatively analyzed by UHPLC-Q-Orbitrap/MS;and its differential saponins revealing different regions screened by the principal component analysis,orthogonal partial least squares discriminant analysis and differential component analysis.RESULTS A total of 62 saponins were identified;saponin variations due to the growth areas verified by the principal component analysis;and 28 differential saponins including 13 protopanaxadiol,6 protopanaxatriol,4 oleanolane,2 oxytetracycline,and 3 C-17 side chain variants further screened by orthogonal partial least-squares discriminant analysis model.The relative contents of protopanaxadiol-type and protopanaxatriol-type saponins in the four producing areas reduced following the order of Liaoning,Jilin,Heilongjiang,and Shandong.CONCLUSION This simple,accurate and efficient method provides a theoretical basis for the quality evaluation of Panacis Quinquefolii Radix.

OBJECTIVE: To investigate the clinical effect of "Tianji" orthopedic robot-assisted percutaneous vertebro plasty(PVP) surgery in the treatment of upper thoracic osteoporotic fracture. METHODS: A retrospective analysis was performed on 32 patients with upper thoracic osteoporotic fracture who underwent PVP surgery in Shenzhen Hospital of Traditional Chinese Medicine from August 2016 to June 2022. There were 8 males and 24 females, ranging in age from 58 to 90 years old, with a mean of (67.75±12.27) years old. Fifteen patients were treated with robot-assisted PVP surgery (robot group), including 3 males and 12 females, with an average age of (68.5±10.3) years. Fracture location:1 case of T₂ fracture, 1 case of T₃ fracture, 3 cases of T₄ fracture, 3 cases of T₅ fracture, and 7 cases of T₆ fracture. The follow-up period ranged from 1.0 to 3.0 months, with a mean of (1.6±0.7) months. Seventeen patients underwent routine PVP surgery (conventional group), including 5 males and 12 females, with an average age of (66.8±11.6) years old. Fracture location:1 case of T₁ fracture, 5 cases of T₄ fracture, 2 cases of T₅ fracture and 9 cases of T₆ fracture. The follow-up period ranged from 0.5 to 4.0 months, with a mean of (1.5±0.6) months. Preoperative and postoperative visual analogue scale(VAS) and Oswestry disability index(ODI) scores were compared between the two groups, and the number of punctures, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage, and intraoperative radiation dose were compared between the two groups. RESULTS: Number of punctures times, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage and intraoperative radiation dose in the robot group were all significantly better than those in the conventional group(P<0.05). VAS of 2.03±0.05 and ODI of (22.16±4.03) % in the robot group were significantly better than those of the robot group before surgery, which were (8.67±0.25) score and (79.40±7.72)%(t=100.869, P<0.001;t=25.456, P<0.001). VAS of 2.17±0.13 and ODI of (23.88±6.15)% in the conventional group were significantly better than those before surgery, which were (8.73±0.18) score and (80.01±7.59)%(t=121.816, P<0.001;t=23.691, P<0.001). There was no significant difference in VAS and ODI between the two groups after operation (t=-3.917, P=0.476;t=-0.922, P=0.364). CONCLUSION Robot-assisted PVP in the treatment of upper thoracic osteoporotic fractures can further improve surgical safety, reduce bone cement leakage, and achieve satisfactory clinical efficacy.
Female ; Male ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Osteoporotic Fractures/surgery* ; Robotics ; Blood Loss, Surgical ; Bone Cements ; Retrospective Studies ; Thoracic Vertebrae/surgery*

Cinnamomum camphora is an important economic tree species in China. According to the type and content of main components in the volatile oil of leaf, C. camphora were divided into five chemotypes, including borneol-type, camphor-type, linalool-type, cineole-type, and nerolidol-type. Terpene synthase(TPS) is the key enzyme for the formation of these compounds. Although several key enzyme genes have been identified, the biosynthetic pathway of(+)-borneol, which has the most economic value, has not been reported. In this study, nine terpenoid synthase genes CcTPS1-CcTPS9 were cloned through transcriptome analysis of four chemical-type leaves. After the recombinant protein was induced by Escherichia coli, geranyl pyrophosphate(GPP) and farnesyl pyrophosphate(FPP) were used as substrates for enzymatic reaction, respectively. Both CcTPS1 and CcTPS9 could catalyze GPP to produce bornyl pyrophosphate, which could be hydrolyzed by phosphohydrolase to obtain(+)-borneol, and the product of(+)-borneol accounted for 0.4% and 89.3%, respectively. Both CcTPS3 and CcTPS6 could catalyze GPP to generate a single product linalool, and CcTPS6 could also react with FPP to generate nerolidol. CcTPS8 reacted with GPP to produce 1,8-cineol(30.71%). Nine terpene synthases produced 9 monoterpene and 6 sesquiterpenes. The study has identified the key enzyme genes responsible for borneol biosynthesis in C. camphora for the first time, laying a foundation for further elucidating the molecular mechanism of chemical type formation and cultivating new varieties of borneol with high yield by using bioengineering technology.
Cinnamomum camphora/enzymology* ; Alkyl and Aryl Transferases/chemistry*

OBJECTIVES: To develop the birth weight curve of singleton neonates with a gestational age of 24-42 weeks, and to investigate the regional differences of the birth weight curve. METHODS: A total of 11 maternal and child health hospitals with more than 7 000 neonates delivered annually were selected in 11 cities of China (Haikou, Guangzhou, Shenzhen, Liuzhou, Guilin, Quanzhou, Chongqing, Chengdu, Changsha, Ningbo, and Lianyungang), and all live singleton neonates delivered in the 11 hospitals from January 1, 2017 to December 31, 2020 were enrolled for the development of birth weight curves. RESULTS: A total of 93 720 singleton neonates with a gestational age of 24-42 weeks from the 11 cities were included in the study. The reference values of the 3rd-97th percentiles of birth weight of singleton neonates for the total of the 11 cities and for each of the 11 cities were established, and the birth weight percentile curves were drawn. The birth weight curve level of singleton neonates in Shenzhen and Quanzhou was almost the same as the average level of the 11 cities; the birth weight curve level of singleton neonates in Haikou, Guangzhou, Guilin, and Liuzhou was slightly lower than the average level of the 11 cities; the birth weight curve level of singleton neonates in Chongqing, Chengdu, and Changsha was slightly higher than the average level of the 11 cities; the birth weight curve level of singleton neonates in Ningbo and Lianyungang was higher than the average level of the 11 cities. The average birth weight curve level of singleton neonates in the 11 cities were very close to that of China Neonatal Cooperation Network in 2011-2014. CONCLUSIONS The reference values of the 3rd-97th percentiles of birth weight of singleton neonates for the total of the 11 cities and for each of the 11 cities are developed, which can be used as a reference for evaluating the intrauterine growth of singleton neonates in the region. The level of intrauterine growth of neonates in some cities is different from the national level.
Birth Weight ; Child ; China ; Cities ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Reference Values

In this study, UPLC-Q-Exactive-MS/MS was used to rapidly analyze the chemical constituents of Meconopsis quintupli-nervia, and the anti-liver fibrosis mechanism of M. quintuplinervia was preliminarily analyzed by network pharmacology, molecular docking, and cell experiments. The chemical constituents of M. quintuplinervia were identified according to the information of MS~1 and MS~2, as well as the data in the literature and databases. SwissTargetPrediction and TargetNet were used to predict the potential targets. The targets related to liver fibrosis were collected from GeneCards and OMIM. The protein-protein interaction(PPI) network was constructed by STRING. Cytoscape 3.6.1 was used to construct and analyze the "constituent-target-disease" network to obtain key targets and their corresponding constituents in the network. DAVID 6.8 was used for GO analysis and KEGG signaling pathway enrichment analysis. Finally, the preliminary verification was carried out by molecular docking and cell experiments. As a result, 106 chemical constituents were identified from M. quintuplinervia, including 66 flavonoids, 16 alkaloids, 18 phenolic acids, 1 anthocyanin, and 5 other constituents. Among them, 3 constituents were identified as potential new compounds, and 59 constituents were reported in M. quintuplinervia for the first time. Network pharmacology analysis showed that M. quintuplinervia presumably acted on AKT1, SRC, JUN, EGFR, STAT3, HSP90 AA1, MAPK3, and other core targets through luteolin, isorhamnetin, quercetin, apigenin, kaempferide, amurine, 2-methylflavinantine, allocryptopine, the multi and other active compounds, thereby regulating the PI3 K/AKT signaling pathway, pathways in cancer, proteoglycans in cancer, FoxO signaling pathway, and other pathways to exert anti-liver fibrosis effects. M. quintuplinervia extract(MQE) could significantly down-regulate PI3 K and AKT protein levels in the HSC-T6 cell model induced by TGF-β1, suggesting that MQE may have the ability to regulate the PI3 K/AKT signaling pathway. The findings of this study indicated that the anti-liver fibrosis effect of M. quintuplinervia had multi-constituent, multi-target, and multi-pathway characteristics, which may provide a scientific basis for the research on the pharmacodynamic materials, action mechanism, and quality markers of M. quintupli-nervia.
Tandem Mass Spectrometry ; Molecular Docking Simulation ; Network Pharmacology ; Proto-Oncogene Proteins c-akt ; Papaveraceae ; Liver Cirrhosis ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVES: To develop the birth weight curve of twin neonates with a gestational age of 25-40 weeks, and to investigate the regional differences of the birth weight curve. METHODS: A total of 11 maternal and child health care hospitals with more than 7 000 neonates delivered annually were selected in 11 cities of China (Haikou, Guangzhou, Liuzhou, Guilin, Quanzhou, Shenzhen, Chongqing, Chengdu, Changsha, Ningbo, and Lianyungang), and all live twin neonates delivered in the 11 hospitals from January 1, 2017 to December 31, 2020 were enrolled for the development of birth weight curves. RESULTS: A total of 17 256 twin neonates with a gestational age of 25-40 weeks from the 11 cities were included in the study. The reference values of the 3rd-97th percentiles of birth weight of twin neonates for the total of the 11 cities and for each of the 11 cities in China were established, and the birth weight percentile curves were drawn. The birth weight curve level of twin neonates in Liuzhou was lower than the average level of the 11 cities; the birth weight curve level of twin neonates in Ningbo was higher than the average level of the 11 cities; the birth weight curve level of twin neonates in Lianyungang was obviously higher than the average level of the 11 cities; the birth weight curve level of twin neonates in other 8 cities was almost the same as the average level of the 11 cities. CONCLUSIONS The reference values of the 3rd-97th percentiles of birth weight of twin neonates for the total of the 11 cities and for each of the 11 cities are developed, which can be used as a reference for evaluating the intrauterine growth of twin neonates in the region. The level of intrauterine growth of twin neonates in some cities is different from the average level of the 11 cities of China.
Birth Weight ; Child ; China ; Cities ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Twins