ObjectiveThe antitumor activity of sesquiterpenoid M36 isolated from Myrrha against human hepatoma HepG2 cells was investigated in this study. MethodHepG2 cells were treated with M36 at different concentrations （0， 2， 4， 6， 8， 10 μmol·L^-1）. Firstly， the effects of M36 on the proliferation of human hepatoma HepG2 cells were detected by methyl thiazolyl tetrazolium （MTT）， colony formation assay， and EdU proliferation assay. Hoechst staining， flow cytometry analysis， and Western blot were used to explore the effect of M36 on the apoptosis of human hepatoma HepG2 cells. Acridine orange staining and western blotting were used to examine the effect of M36 on autophagy in HepG2 cells. Finally， Western blot was used to detect protein expression of cancer-related signaling pathways. ResultCompared with the blank group， M36 treatment significantly inhibited the proliferation of human hepatoma HepG2 cells （P<0.01）， and the half inhibitory concentration （IC₅₀） value of M36 for 48 h was 5.03 μmol·L^-1， in a dose- and time-dependent manner. M36 was also able to induce apoptosis and autophagy in human hepatoma HepG2 cells. After treatment with 8 μmol·L^-1 M36 for 48 hours， the apoptosis rate of HepG2 cells was （42.03±9.65）% （P<0.01）. Compared with the blank group， HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h had a significant increase in cleaved poly ADP-ribose polymerase （cleaved-PARP） protein levels （P<0.01）. Acridine orange staining showed that autophagy was significantly activated in HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h compared with the blank group （P<0.01）， which was further verified by the up-regulation of microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. Western blot results showed that compared with the blank group， the levels of phosphorylated extracellular regulated protein kinase （p-ERK）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， phosphorylated c-Jun N-terminal kinase （p-JNK）， and its downstream nuclear transcription factors c-Jun and p-c-Jun protein were significantly increased in M36 group （P<0.05， P<0.01）. The mechanism may be related to the up-regulation of MAPK signaling pathway. ConclusionThe sesquiterpenoid M36 isolated from Myrrha inhibits the proliferation of human hepatoma HepG2 cells and promotes apoptosis and autophagy， which may be related to the activation of the MAPK signaling pathway.

The long-term efficacy and complications of implantable diaphragm pacer (IDP) in a child with cervical spinal cord injury (CSCI) in the Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center in September 2022 were retrospective analyzed.A male child had quadriplegia without an obvious cause at the age of 12 years, and he was then lived completely with the assistance of mechanical ventilation.At the age of 14 years, he could wean off the ventilator in unilateral diaphragmatic pacing mode.However, mechanical ventilation was re-given for months after 5 years due to pneumonia, and then the IDP was re-given with the self-felt decreased pacing effect.After hospitalization, the patient was examined with mild diaphragmatic atrophy, secondary flat chest, and mild scoliosis.After optimization of the transdiaphragmatic pacing threshold and rehabilitation, his respiratory function improved.IDP can be used in CSCI for long time, while flat chest and scoliosis that limited the expansion of the lungs should be considered.At the meantime, the increased abdominal spasm affected the abdominal compliance, leading to the decrease in the efficiency of the diaphragm.

Objective To explore the cost structure and influencing factors of high-multiplication cases.Methods Using medical insurance settlement data from a tertiary hospital in Tianjin from April 2023 to March 2024,this study analyzes the characteristics of high-multiplication DRG cases and compares hospitalization costs between high-multiplication and normal-multi-plication patients.The grey relational analysis method is employed to assess the grey correlation between hospitalization costs and various itemized expenses for both groups.Results Significant differences were found between the high-multiplication group and the normal-multiplication group in terms of gender,age,insurance type,length of stay,base points,and all hospitalization costs except for surgical expenses(P＜0.05).Within the cost structure,drug costs from multiple DRG groups showed the strongest correlation with total hospitalization costs.Treatment costs ranked highest in overall grey correlation.Conclusion Enhancing the management of high-multiplication cases is crucial.Future efforts should focus on improving separate payment policies for high-multiplication and special cases,refining clinical pathways,standardizing medical practices,optimizing performance distribution methods,and strengthening operational management to enhance the fine management of medical insurance.

  Objective  To understand the current status of surgical treatment for hemophilia osteoarthropathy (HO) in China.  Methods  Using an online questionnaire, select domestic hospitals that partici-pated in the compilation of the 'Guideline for perioperative management of hemophilia patients undergoing orthopaedic surgery in China ', in addition to members of the National Joint Surgery Group, and the Orthopedic Branch of the Chinese Medical Association for targeted investigation and analysis.  Results  A total of 17 domestic hospitals were included, all of which were general hospitals. Hospitals that started HO surgery treatment before 2000 accounted for 35.29%. A total of 3057 surgical cases of HO were reported by those hospitals. The most commonly performed surgical procedures were hip and knee joint replacement. The most commonly used coagulation factor replacement regimen was recombinant coagulation factor preparation. Ten hospitals reported finding patients with transfusion-related infectious diseases. Bleeding and hematoma formation were the most frequently reported surgical complications. Excessive length of hospital stay and high economic costs were the most frequently reported problems.  Conclusions  Surgical treatment for HO in 17 hospitals is mainly carried out in some large comprehensive medical centers in the eastern region. Compared with the patient base, the popularity and number of surgeries are still relatively insufficient. It is necessary to further standardize the treatment system by standardizing factor replacement and strengthening rehabilitation to improve surgical treatment outcomes.

Objective:To investigate the efficacy of metagenomic next generation sequencing (mNGS) in the etiological diagnosis of patients with spinal infection, so as to provide reference for timely diagnosis and treatment.Methods:A total of 40 patients with suspected spinal infection admitted to the Department of Infectious Diseases in Henan Provincial People′s Hospital from January 2020 to July 2022 were included. The results of tissue culture, histopathological examination and tissue mNGS detection were analyzed retrospectively. According to the clinical diagnose, the patients were divided into the spinal infection group (28 cases) and the non-spinal infection group (12 cases). The positive rate, sensitivity and specificity of mNGS and tissue culture in the pathogen detection of patients with spinal infection were compared. McNemar test was used for statistical analysis.Results:There were 23 males and 17 females in 40 patients. The positive rate of mNGS was higher than that of tissue culture (75.0%(30/40) vs 12.5%(5/40)), and the difference was statistically significant ( χ2=0.08, P<0.001). Based on clinical diagnostic criteria, the sensitivity of mNGS in the diagnosis of spinal infection was higher than that of tissue culture (82.1% vs 17.9%), with a statistically significant difference ( χ2=0.02, P<0.001), while the specificity compared to the tissue culture (33.3% vs 100.0%), the difference was not statistically significant ( P>0.05). Conclusions:mNGS has a high pathogen detection rate and sensitivity in the etiological diagnosis of patients with spinal infection, which could provide clinical guidance for the diagnosis and treatment of patients with spinal infection.

The American College of Rheumatology (ACR) and the American Association of Hip and Knee Surgeons (AAHKS) convened a writing group to develop a consensus report on the management of anti-rheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty in June 2022. In particular, the consensus provides significant updates on target synthetic disease modifying anti-rheumatic drugs and perioperative medication management in patients with systemic lupus erythematosus, as well as the addition of newly approved antirheumatic medications for administration. This article will interpret the consensus and provide a reference for the perioperative management of antirheumatic medications for hip and knee arthroplasty in patients with rheumatic diseases in China.

Objective:To investigate the perioperative total blood loss of robot-assisted total knee arthroplasty (TKA).Methods:A total of 60 patients with knee osteoarthritis who underwent initial unilateral TKA in Peking Union Medical College Hospital from February to June 2022 were retrospectively analyzed. According to whether they received robot-assisted surgery, they were divided into robot-assisted group and traditional surgery group. In the robot-assisted group, there were 32 patients, including 6 males and 26 females, aged 70.22±5.88 years (range, 57 to 79 years). Left side 14 cases, right side 18 cases; grade of Kellgren-Lawrence: 1 case of grade Ⅱ, 14 cases of grade Ⅲ, 17 cases of grade Ⅳ. In the traditional surgery group, there were 28 patients, including 5 males and 23 females, aged 68.61±6.79 years (range, 57 to 87 years). Left side 16 cases, right side 12 cases; grade of Kellgren-Lawrence: 2 cases of grade Ⅱ, 12 cases of grade Ⅲ, 14 cases of grade Ⅳ. There was no significant difference in baseline data between the two groups ( P>0.05). Postoperative hemoglobin, hematocrit, and their decreased values were recorded in the two groups, and perioperative range of motion (ROM) of knee and Hospital for Special Surgery (HSS) scores were compared between the two groups. Results:All patients successfully completed the surgery and were followed up, with a follow-up time of 9.93±0.83 months (range, 8-11 months) in the robotic-assisted group and 9.59±0.97 months (range, 8-11 months) in the traditional surgery group. The application time of tourniquet in the robot-assisted group was 96.19±10.21 min, which was higher than that in the traditional surgery group (62.68±16.54 min), and the difference was statistically significant ( t=9.57, P<0.001). The total perioperative blood loss in the robot-assisted group was 534.59(411.85, 859.26) ml, which was higher than 411.32(313.42, 613.52) ml in the traditional surgery group, and the difference was statistically significant ( Z=-2.37, P=0.018). There were no significant differences in hemoglobin or hematocrit between the two groups at day 1 and 3 after surgery ( P>0.05). The hemoglobin decrease value in the robotic-assisted group was 19.63±9.73 g/L, which was greater than 14.71±5.84 g/L in the traditional surgery group, and the difference was statistically significant ( t=2.40, P=0.020). The decrease value of hematocrit in the robot-assisted group was 5.77%±3.14%, which was greater than 4.09%±1.57% in the traditional operation group ( t=2.56, P=0.013). At the last follow-up, knee ROM of the two groups were 123.03°±5.91° and 125.82°±6.59°, respectively, which were higher than the preoperative values of 95.69°±11.64° and 90.29°±23.08°. Postoperative HSS scores were 89.50±4.19 points and 90.70±4.34 points, which were higher than 62.58±10.52 points and 61.09±12.66 points before operation, the differences were statistically significant ( P<0.05), and there was no significant difference between groups ( P>0.05). There were 6 cases of postoperative deep vein thrombosis of the lower extremities in the robot-assisted group and 2 cases in the traditional surgery group, and the difference was not statistically significant (χ 2=0.88, P=0.348). Conclusion:Compared with traditional TKA, robotic-assisted TKA increased perioperative blood loss, and there was no difference in postoperative knee function between the two groups.

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

Objective:To analyze the liver pathological characteristics of chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) and negative hepatitis B e antigen (HBeAg), and to evaluate the diagnostic value of different serological models for liver fibrosis.Methods:Retrospective analysis was conducted on the patients with HBeAg-negative CHB who had normal ALT and underwent liver biopsy from August 2016 to December 2019 in the Department of Infectious Diseases, Henan Provincial People′s Hospital. The clinical data, serum indicators of hepatitis B virus (HBV) and HBV DNA were collected. The liver fibrosis stages (S) was assessed by pathological examination. The diagnostic efficacies of gamma-glutamyl transpeptidase to platelet ratio (GPR), fibrosis 4 score (FIB-4), S index, aspartate aminotransferase to platelet ratio index (APRI) and gamma-glutamyl transpeptidase to albumin ratio (γ-GT/ALB) for liver pathological fibrosis were analyzed by the receiver operating characteristic curves. Two variable correlation test was used to explore the relationship between the different models and pathological fibrosis of liver tissue. Chi-square test was used for statistical comparison.Results:The age of 448 patients was (37.98±9.82) years, and the male to female ratio was 1.286 ∶1. The proportions of S≥2 in patients with age>30 years, hepatitis B surface antigen (HBsAg)<2 000 IU/mL and HBV DNA≥2 000 IU/mL were higher than those in patients with age ≤30 years, HBsAg ≥2 000 IU/mL and HBV DNA<2 000 IU/mL, respectively, and the differences were all statistically significant ( χ2=7.68, P=0.006; χ2=11.44, P=0.001; χ2=9.12, P=0.003, respectively). There were 250 cases with pathological fibrosis stage S<2, 162 cases with S=2 and 36 cases with S≥3. FIB-4 (correlation coefficient 0.250), APRI (correlation coefficient 0.218), GPR (correlation coefficient 0.186), S index (correlation coefficient 0.184) and γ-GT/ALB (correlation coefficient 0.127) were positively correlated with the severity of liver fibrosis (all P<0.050). S index had the highest sensitivity (64.1%) in the diagnosis of significant liver fibrosis (S≥2), while γ-GT/ALB had the highest specificity (80.8%). In the diagnosis of severe liver fibrosis (S≥3), γ-GT/ALB had the highest sensitivity (77.8%), while APRI had the highest specificity (78.6%). Conclusions:The incidence of liver fibrosis in CHB patients with normal ALT and negative HBeAg is relatively high. The current serological diagnostic models are not suitable for the evaluation of liver fibrosis in these patients, and timely liver puncture is still necessary.

Objective:To analyze the hepatic pathological inflammation and fibrosis condition in order to explore the relationship with related clinical indicators in patients with chronic hepatitis B patients with normal alanine aminotransferase (ALT).Methods:721 cases of chronic hepatitis B with normal ALT who were initially diagnosed in the Department of Infectious Diseases of Henan Provincial People's Hospital from August 2016 to December 2019 were retrospectively collected. Liver biopsy was performed in all patients. General data of patients such as gender, age, liver function indexes, blood routine indexes, HBsAg level, HBeAg status, HBV DNA level, spleen thickness and prothrombin time were collected. Univariate and multivariate analysis methods were used to determine the influencing factors of inflammation and fibrosis degree with liver biopsy. A receiver operating characteristic curve (ROC) was used to evaluate the established multi-factor prediction model. Alpha=0.05 was considered as a standard orientation of test.Results:The average age of 721 cases with chronic hepatitis B was 36.1±9.7 years, and the male to female ratio was 1.28/1, with inflammation and fibrosis grade mainly concentrated in G1S1 (349 cases), G1S2 (132 cases), G2S2 (119 cases), and G2S1 (57 cases). Among them, there were 349 (48.4%) cases of G1S1, and 372 (51.6%) cases of G/S≥2. The main manifestations were mild to moderate inflammation and fibrosis, and only 64 (8.88%) cases had severe G/S≥3. HBsAg level (stratified with 4 log10 IU/ml as the boundary) analyzed in 721 cases were correlated with the relevant clinical indicators stratification and liver pathological inflammation and fibrosis, and the difference was statistically significant (inflammation grade, χ2=6.182, P=0.013; Fibrosis grade, χ2=36.534, P=0.001). Univariate analysis of the relevant clinical indicators that may influence the patient's liver pathological G/S ≥2 showed the patient's age, albumin, γ- glutamyltransferase (GGT), platelet, prothrombin time (PT), spleen thickness and HBsAg level were all statistically significant ( P<0.05), while multivariate analysis showed that age, GGT, PT, and spleen thickness had statistical differences ( P<0.05). The prediction model was established in accordance to multivariate analysis, and the area under the ROC curve was 0.642. Maximization of the sum of sensitivity and specificity as cut-off value of Logit P=0.497, the diagnostic sensitivity, specificity, and Youden's index were 60.6%, 64.5%, and 0.252, respectively. Conclusion:More than half of patients with chronic hepatitis B with normal ALT have significant inflammation and fibrosis and require timely antiviral therapy. Age, GGT, PT and spleen thickness can help comprehensively evaluate the liver inflammation and fibrosis status among patients, but the lack of accurate prediction models suggests that more effective indicators that can help predict the inflammation and fibrosis status of such patients have yet to be discovered. Therefore, liver biopsy should still be actively performed in patients with normal ALT to confirm the diagnosis and timely treatment.