Exploration on ALT threshold for initiating antiviral therapy in chronic HBV-infected patients based on results of 707 liver puncture cases / 中国热带医学

@#Abstract: Objective To explore the threshold of ALT for initiating antiviral therapy in HBV infected patients, and to provide a basis for initiating antiviral therapy in chronic HBV-infected patients. Methods This retrospective cohort study recruited 707 consecutive treatment-naïve chronic hepatitis B (CHB) patients undergoing diagnostic liver biopsy in the department of infectious diseases of the Affiliated Hospital of Yan′an University from October 2013 to August 2018. Liver biopsy specimens were obtained under ultrasound guidance using Menghini 16G disposable needles. The METAVIR scoring system, which is commonly used internationally, was used to divide the patients into the group with mild liver tissue injury and the group with significant liver tissue injury, and the alanine aminotransferase (ALT) levels were measured separately. Receiver operating characteristic (ROC) curve and Mann-Whitney U test were used to evaluate the diagnostic value of ALT for significant liver tissue injury under different demographic characteristics. Results Of 707 patients, 292 (41.30%) had significant liver tissue injury confirmed by liver biopsy (METAVIR ≥A2 and/or F2). When the ULN of ALT was set to NICE criteria (30 U/L for males, 19 U/L for females), AASLD criteria (35 U/L for males, 25 U/L for females) and EASL or APASL criteria (40 U/L for males and females), CHB patients with <ULN accounted for 32.38%, 35.03% and 36.07% of significant liver tissue injury, respectively. And significant liver tissue injury in CHB patients with 1-2×ULN accounted for 41.99%, 41.85% and 50.30%, respectively. The optimal ALT critical values were 33 U/L for overall patients, 25 U/L for females, 45 U/L for males, 45 U/L for ≤30 years olds, 33 U/L for>30 years olds, 22 U/L for HBeAg negative and 31 U/L for HBeAg positive patients. Conclusions The threshold of ALT for initiating antiviral therapy in chronic HBV patients should be individualized, especially should be down-regulated for the females, olders and HBeAg-negative patients.

"Graded early warning system" of RET germline mutation carriers in MEN2A/MEN2B families and total thyroidectomy (report of 7 cases) / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the reasonable time of prophylactic thyroidectomy for RET gene carriers in multiple endocrine neoplasia(MEN) 2A/2B families. Methods: From May 2015 to August 2021, RET gene carriers in MEN2A/MEN2B families were dynamically followed up at the Department of Thyroid Head and Neck Surgery, Beijing Tongren Hospital of Capital Medical University. The high-risk patients were encouraged to undergo prophylacitc total thyroidectomy according to the principle of "graded early warning system", namely the evaluation of gene detection, calcitonin value and ultrasound examination successively. Seven cases underwent the surgery, including 3 males and 4 females, aged from 7 to 29 years. According to the risk stratification listed in the guidelines of the American Thyroid Association in 2015, there were 2 cases of the highest risk, 2 cases of the high risk and 3 cases of the modest risk. Calcitonin index remained within the normal range in 3 cases and elevated in 4 cases before operation. All 7 patients underwent thyroidectomy with lymph node dissection of the level Ⅵ performed in 4 patients. Results: The time from suggestion to operation was 2 to 37 months, with an average of 15.1 months. The 6 patients were medullary thyroid carcinoma and 1 case with C-cell hyperplasia. The follow-up time was 2 to 82 months, with an average of 38.4 months. Postoperative serum calcitonin levels of all cases decreased to normal level, with biochemical cure. There was no sign of recurrence on ultrasound examination. All 7 patients had no serious complications, no obvious thyroid dysfunction. Their height, weight and other indicators of pediatric patients were similar to those of their peers, with normal growth and development. Conclusion: For healthy people with MEN2A/MEN2B family history, prophylactic thyroidectomy can be carried out selectively based on the comprehensive evaluation of "graded early warning system" with strict screening and close monitoring.

Clinicopathological features of gastric carcinomas with NTRK-rearrangement/amplification: report of four cases / 中华病理学杂志

Objective: To investigate the clinicopathological, immunohistochemical and molecular genetic characteristics of gastric carcinoma with NTRK-rearrangement/amplification. Methods: The clinicopathological data of gastric carcinoma cases with NTRK-rearrangement/amplification diagnosed from January 2011 to September 2020 at the Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, China, were collected. The clinicopathological, immunophenotypic and molecular pathological features were analyzed. The relevant literature was reviewed. Results: There were 4 cases of gastric carcinoma with NTRK-rearrangement/amplification. All 4 patients were male, aged 57-67 years (average, 63 years). Tumor sizes ranged from 3.5 to 5.2 cm (average, 4.8 cm). All tumors were in the antrum. All 4 patients underwent radical gastrectomy and were followed up after the surgery. Morphologically, all tumors showed histological features with enteroblastic-differentiated gastric carcinoma. Tumor cells showed predominantly tubular/papillary architecture, with conspicuous vesicular nuclei and pale staining or transparent cytoplasm. Immunohistochemistry showed pan-TRK expression in all cases, with various degrees of positivity in the cytoplasm. All cases were subject to NTRK1/2/3 detection using fluorescence in situ hybridization. There were NTRK translocations in 2 cases and NTRK amplifications in 2 cases. These cases were further verified by RNAseq next generation sequencing which confirmed that NTRK1 gene translocation (TPM3-NTRK1) and NTRK2 gene translocation (NTRK2-SMCHD1) occurred in two cases, respectively. Conclusions: NTRK mutation occurs less frequently in gastric cancer. In this study, the cases mainly occur in the antrum. The morphology has the characteristics of enteroblastic differentiation. The tumors have unique histological, immunophenotypic and molecular characteristics, which require much attention from pathologists to effectively guide clinicians to choose the best treatment.

Circular RNA expression profiles and circRNA-miRNA-mRNA crosstalk in pre-eclamptic placenta / 中华妇产科杂志

Objective: To identify the expression profile of circular RNA (circRNA) in placenta of pre-eclampsia (PE) pregnant women by high-throughput sequencing, and to construct the circRNA-microRNA (miRNA)-messenger RNA (mRNA) interaction network, so as to reveal the related pathways and regulatory mechanisms of PE. Methods: The clinical data and placentas of 42 women with PE (PE group) and 30 normal pregnant women (control group) who delivered in West China Second University Hospital from November 2019 to June 2021 were collected. (1) High-throughput sequencing was used to establish the differentially expressed circRNA profiles in placental tissues of 5 pairs of PE group and the control group. (2) Real-time quantitative PCR (qRT-PCR) was used to verify the expression levels of 6 differentially expressed circRNAs in placental tissues of PE group and control group. (3) Bioinformatics analysis was used to predict the target miRNA and analyze the co-expressed mRNA to construct a competitive endogenous RNA (ceRNA) network. The differentially expressed circRNAs were analyzed by Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways. (4) Logistic regression analysis, Pearson correlation and Kendall's tau-b correlation analysis were used to test the correlation between the three differentially expressed circRNAs and the risk of PE and clinical characteristics. (5) circRNA_05393 was selected for subsequent functional study. Small interfering RNA (siRNA) and overexpression plasmid were used to knock down or increase the expression level of circRNA_05393 in trophoblast cell line HTR-8/SVneo cells, respectively. Transwell assay was used to detect the migration and invasion ability of the trophoblasts in vitro. Cell counting kit-8 assay was used to detect the proliferation ability of the trophoblasts. Results: (1) Seventy-two differentially expressed circRNAs were identified by high-throughput sequencing, of which 35 were up-regulated and 37 were down-regulated. (2) qRT-PCR showed that compared with the control group, circRNA_00673 (1.306±0.168 vs 2.059±0.242; t=2.356, P=0.021) and circRNA_07796 (1.275±0.232 vs 1.954±0.230; t=2.018, P=0.047) were significantly increased, while circRNA_05393 (1.846±0.377 vs 0.790±0.094; t=3.138, P=0.002) was significantly decreased. (3) The circRNA-miRNA-mRNA interaction network contained 3 circRNAs, 8 miRNAs and 53 mRNAs. GO functional annotation analysis showed that the biological process was mainly enriched in iron ion homeostasis, membrane depolarization during action potential and neuronal action potential. In terms of cellular components, they were mainly enriched in cytoskeleton and membrane components. In terms of molecular function, they were mainly enriched in the activity of voltage-gated sodium channel and basic amino acid transmembrane transporter. KEGG pathway enrichment analysis showed that mRNAs in the interaction network were mainly enriched in complement and coagulation cascade, glycine, serine and threonine metabolism, p53 signaling pathway and peroxisome proliferators-activated receptors (PPAR) signaling pathway. (4) Logistic regression analysis showed that down-regulation of circRNA_05393 expression was a risk factor for PE (OR=0.044, 95%CI: 0.003-0.596; P=0.019). Correlation analysis showed that circRNA_05393 was significantly correlated with systolic blood pressure and diastolic blood pressure in PE pregnant women (both P<0.05). (5) Knock down or overexpression of circRNA_05393 significantly reduced or increased the migration and invasion abilities of HTR-8/SVneo cells (all P<0.05), but had no significant effect on the ability of tube formation and proliferation (all P>0.05). Conclusions: The construction of circRNA expression profile in placenta and the exploration of circRNA-miRNA-mRNA interaction network provide the possibility to reveal the regulatory mechanism of specific circRNA involved in PE. Inhibition of circRNA_05393 may induce the progression of PE by reducing the migration and invasion of trophoblasts.

Relationship between the gross motor function classification system and hip and lumbar spine development in children with spastic cerebral palsy / 中国骨伤

OBJECTIVE@#To investigate the relationship among the gross motor function classification system (GMFCS)and the development of hip joint and lumbar spine in children with spastic cerebral palsy.@*METHODS@#The clinical data of 125 children with spastic cerebral palsy admitted from January 2018 to July 2021 were retrospectively analyzed. There were 85 males and 40 females, aged from 4 to 12 years old with an average of (8.4±2.9) years. According to GMFCS, the patients were divided into gradeⅠ, Ⅱ, Ⅲ and Ⅳ groups. There were 27 cases in gradeⅠgroup, 40 cases in gradeⅡgroup, 35 cases in grade Ⅲ group and 23 cases in grade Ⅳ group. The migration percentage(MP), central edge angle(CE), neck-shaft angle(NSA), acetabular index(AI) were measured by the radiograph of pelvis, abnormal parameters were selected to evaluate the relationship between different GMFCS grades and hip joint development. Lumbar sagittal Cobb angle, lumbar sacral angle, lumbar lordosis index and apical distance were measured by lateral lumbar radiographs to evaluate the relationship between different GMFCS grades and lumbar spine development.@*RESULTS@#①Among the 125 spastic cerebral palsy children, there were 119 cases of pelvic radiographs that met the measurement standards. In the four groups with gradeⅠ, Ⅱ, Ⅲ, Ⅳ, MP was (22.72±3.88), (26.53±4.36), (33.84±4.99), and (49.54±7.87)%, CE was(30.10±6.99) °, ( 22.92±4.19) °, ( 17.91±5.50) °, and (-0.70±17.33)°, AI was (16.41±2.77) °, (20.46±4.63) °, (23.76±5.10) °, and ( 29.15±7.35)°, respectively, there were significant differences between the two comparisons (P<0.05). And the higher GMFCS grade, the greater MP and AI, and the smaller CE.The NSA was(142.74±10.03) °, (148.66±9.09) °, (151.66±10.52) °, and (153.70±8.05)° in four groups with gradeⅠ, Ⅱ, Ⅲ, Ⅳ, respectively. The differences between the two comparisons of the GMFCS gradeⅠgroup and the other three groups were statistically significant (P<0.05). NSA of GMFCSⅠgroup was significantly lower than that of the others, there was no significant difference among other groups(P>0.05). ② Among the 125 spastic cerebral palsy children, there were 88 cases of lumbar spine radiographs that met the measurement standards. ③The lumbar sagittal Cobb angle was(32.62±11.10) °, (29.86±9.90) °, (31.70±11.84) °, and (39.69±6.80)° in the four groups with gradeⅠ, Ⅱ, Ⅲ, Ⅳ, respectively;GMFSS of grade Ⅳ group was significantly higher than that of other three groups, there was significant difference between the two comparisons (P<0.05);there were no significant differences between other groups (P>0.05). In the four groups with gradeⅠ, Ⅱ, Ⅲ, Ⅳ, the lumbosacral angle was (31.02±9.91) °, ( 26.57±9.41) °, (28.08±8.56) °, and ( 27.31±11.50)°, the lumbar lordosis index was (4.14±12.89), (8.83±13.53), (13.00±11.78), and (10.76±9.97) mm, the arch apex distance was (9.50±6.80), (6.68±3.20), (7.16±4.94), and (6.62±4.13) mm, respectively, there were no significant differences between the two comparisons(P>0.05).@*CONCLUSION@#①In children with GMFCS gradeⅠ-Ⅳ, the higher the GMFCS grade, the worse the hip develops. ② Children with GMFCS grade Ⅲ-Ⅳ may be at greater risk for lumbar kyphosis.

Mutation of dentin sialophosphoprotein and hereditary malformations of dentin / 中华口腔医学杂志

The classification as well as the clinical manifestations of hereditary malformations of dentin are of great concern and have been deeply elucidated. The understanding of its genetic basis also increases progressively. Dentin sialophosphoprotein (DSPP) is the pathogenic gene of dentinogenesis imperfecta type Ⅱ, dentinogenesis imperfecta type Ⅲ and dentin dysplasia type Ⅱ. In this article, the classification of DSPP mutations as well as the resultant dysfunction of the mutant DSPP are summarized respectively and the corresponding clinical manifestations are analyzed. This work will provide a reference for the diagnosis and treatment of hereditary malformations of dentin.

Advances in animal models of chronic heart failure and its applications in traditional Chinese medicine / 中国中药杂志

Chronic heart failure(CHF) is a series of clinical syndromes in which various heart diseases progress to their end stage. Its morbidity and mortality are increasing year by year, which seriously threatens people's life and health. The diseases causing CHF are complex and varied, such as coronary heart disease, hypertension, diabetes, cardiomyopathy and so on. It is of great significance to establish animal models of CHF according to different etiologies to explore the pathogenesis of CHF and develop drugs to prevent and treat CHF induced by different diseases. Therefore, based on the classification of the etiology of CHF, this paper summarizes the animal models of CHF widely used in recent 10 years, and the application of these animal models in traditional Chinese medicine(TCM) research, in order to provide ideas and strategies for studying the pathogenesis and treatment of CHF, and provide ideas for TCM modernization research.

Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version) / 中国中药杂志

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

Implementation Status of Palliative Care for Patients Died in Peking Union Medical College Hospital,2019 / 中国医学科学院学报

Objective To reveal the current situation of palliative care for patients who died in Peking Union Medical College Hospital,so as to guide the practice of palliative care for patients in terminal stage. Methods A retrospective study was conducted on patients who died in Peking Union Medical College Hospital from January 1,2019 to December 31,2019.The general clinical data of the patients,whether they received palliative care,and the treatment details including invasive rescue measures,symptom controlling,and psychological,social,and spiritual care status before dying were collected for descriptive analysis. Results A total of 244 inpatients died in 2019,including 135 males and 109 females,with an average age of (65.9±16.4) years (1 day to 105 years).Among the 244 patients,112 (45.9%) died of neoplastic diseases and 132 (54.1%) died of non-neoplastic diseases.Sixty-one (25.0%) patients received palliative care before death,and they were mainly distributed in internal medicine departments such as nephrology (100.0%),gastroenterology (80.0%),and geriatrics (72.7%).Twenty-nine patients received sound palliative care,with all symptoms under control and no invasive treatment before death,and twenty-six patients received psychological,social,and spiritual care.Compared with the patients who were not exposed to the concept of palliative care,the patients who received palliative care showed decreased probabilities of cardiopulmonary resuscitation (0 vs 20.2%;χ2=13.009,P<0.001),tracheal intubation (3.3% vs 48.6%;χ2=38.327,P<0.001),and invasive mechanical ventilation (4.9% vs 47.5%;χ2=33.895,P<0.001) and an increased probability of psychological,social,and spiritual care (54.1% vs 2.4%;χ2=91.486,P<0.001). Conclusion The concept of palliative care has a positive impact on the death of end-stage patients.Palliative care services can increase the probability of end-stage patients receiving psychological,social,and spiritual care and reduce the use of invasive treatment.

Standard Process for Palliative Sedation in Peking Union Medical College Hospital / 中国医学科学院学报

End-stage patients experience unbearable pain because of refractory symptoms.Palliative sedation is a form of palliative care which relieves patients' agony by lowering their consciousness.Standard palliative sedation can help patients die with dignity.It is distinct from euthanasia and does not alter the survival of patients.Sufficient palliative care is the premise of palliative sedation.Repeated and detailed clinical evaluation,as well as multidisciplinary involvement,is necessary for the standardized implementation of palliative sedation.Here,we proposed the standard process and specifications of palliative sedation in Peking Union Medical College Hospital.Furthermore,we reported a case of palliative sedation for an advanced cancer patient with refractory delirium and living pain to demonstrate its application in clinical practice.

Research progress on structure, function and disease correlation of solute carrier family 4 / 生理学报

The solute carrier family 4 (SLC4) includes 10 members (SLC4A1-5, SLC4A7-11), which are expressed in multiple tissues in the human body. The SLC4 family members differ in their substrate dependence, charge transport stoichiometry and tissue expression. Their common function is responsible for the transmembrane exchange of multiple ions, which is involved in many important physiological processes, such as erythrocyte CO2 transport and the regulation of cell volume and intracellular pH. In recent years, many studies have focused on the role of SLC4 family members in the occurrence of human diseases. When SLC4 family members have gene mutations, a series of functional disorders will occur in the body, leading to the occurrence of some diseases. This review summarizes the recent progress about the structures, functions and disease correlation of SLC4 members, in order to provide clues for the prevention and treatment of related human diseases.

Yinlai Decoction Protects Microstructure of Colon and Regulates Serum Level of D-Lactic Acid in Pneumonia Mice Fed with High-Calorie and High-Protein Diet / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD).@*METHODS@#Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice.@*RESULTS@#The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05).@*CONCLUSIONS@#YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.

Prevalence and clinical implications of polypharmacy and potentially inappropriate medication in elderly patients with heart failure: results of six months' follow-up / 老年心脏病学杂志（英文版）

OBJECTIVES@#To investigate the prevalence of polypharmacy and potentially inappropriate medication (PIM) in elderly patients with heart failure (HF) and their impact on readmission and mortality.@*METHODS@#We conducted a study of 274 participants aged 60 years or older with HF. The prevalence of polypharmacy (defined as the use of five or more medications) was calculated, and the 2019 American Geriatrics Society Beers criteria were applied to access PIMs. Medications and PIMs were characterized at admission and discharge, and changes in prescriptions during hospitalization were compared. The impact of polypharmacy and PIM on readmission and mortality were investigated.@*RESULTS@#The median age of this study population was 68 years old. The median number of prescribed drugs was 7 at admission and 10 at discharge. At discharge, 99.27% of all patients were taking five or more drugs. The incidence of composite endpoint and cardiovascular readmission increased with the number of polypharmacy within 6 months. The use of guideline-directed medical therapy reduced the incidence of composite endpoint events and cardiovascular readmission, while the use of non-cardiovascular medications increased the composite endpoint events. The frequency of PIMs was 93.79% at discharge. The incidence of composite endpoint events increased with the number of PIMs. "PIMs in older adults with caution" increased cardiovascular readmission and "PIMs based on kidney function" increased cardiovascular mortality. Several comorbidities were associated with cardiovascular mortality or non-cardiovascular readmission.@*CONCLUSIONS@#Polypharmacy and PIM were highly prevalent in elderly patients with HF, and their use was associated with an increased risk of composite endpoint events, readmission and mortality. Non-cardiovascular medications, "PIMs in older adults with caution", "PIMs based on kidney function" and several comorbidities were important factors associated with hospital readmission and mortality. Our findings highlight the importance of medication optimization in the management of HF in elderly patients.

Postmortem Interval Estimation Using Protein Chip Technology Combined with Multivariate Analysis Methods / 法医学杂志

OBJECTIVES@#To estimate postmortem interval (PMI) by analyzing the protein changes in skeletal muscle tissues with the protein chip technology combined with multivariate analysis methods.@*METHODS@#Rats were sacrificed for cervical dislocation and placed at 16 ℃. Water-soluble proteins in skeletal muscles were extracted at 10 time points (0 d, 1 d, 2 d, 3 d, 4 d, 5 d, 6 d, 7 d, 8 d and 9 d) after death. Protein expression profile data with relative molecular mass of 14 000-230 000 were obtained. Principal component analysis (PCA) and orthogonal partial least squares (OPLS) were used for data analysis. Fisher discriminant model and back propagation (BP) neural network model were constructed to classify and preliminarily estimate the PMI. In addition, the protein expression profiles data of human skeletal muscles at different time points after death were collected, and the relationship between them and PMI was analyzed by heat map and cluster analysis.@*RESULTS@#The protein peak of rat skeletal muscle changed with PMI. The result of PCA combined with OPLS discriminant analysis showed statistical significance in groups with different time points (P<0.05) except 6 d, 7 d and 8 d after death. By Fisher discriminant analysis, the accuracy of internal cross-validation was 71.4% and the accuracy of external validation was 66.7%. The BP neural network model classification and preliminary estimation results showed the accuracy of internal cross-validation was 98.2%, and the accuracy of external validation was 95.8%. There was a significant difference in protein expression between 4 d and 25 h after death by the cluster analysis of the human skeletal muscle samples.@*CONCLUSIONS@#The protein chip technology can quickly, accurately and repeatedly obtain water-soluble protein expression profiles in rats' and human skeletal muscles with the relative molecular mass of 14 000-230 000 at different time points postmortem. The establishment of multiple PMI estimation models based on multivariate analysis can provide a new idea and method for PMI estimation.

Risk factors for infections after arthroscopic rotator cuff repair / 中国骨伤

OBJECTIVE@#To explore risk factors for infections after arthroscopic rotator cuff repair, and improve the under standing for reducing infection.@*METHODS@#Clinical data of 2 591 patients who underwent arthroscopic rotator cuff repair from January 2019 to January 2022 were retrospectively analyzed, including 1 265 males and 1 326 females, aged from 25 to 82 years old with an average age of (51.5±15.6) years old. They were divided into infection group(n=18) and uninfected group(n=2 573) according to whether or not patients had postoperative infection. Gender, age, smoking, diabetes, body mass index, local closure within 1 month before operation, operation time, preventive use of antibiotics, and internal fixation implantation between two groups were recorded. Univariate Logistic regression analysis screened factors associated with infections after arthroscopic rotator cuff repair. Theresultswere entered into the multivariate logistic regression analysis, screening the high risk factors for infections after arthroscopic rotator cuff repair.@*RESULTS@#In 2 591 patients, 18 patients were infected after operation, infection rate was 0.69%. Univariate Logistic regression analysis showed that gender, age, operation time, antibiotic prophylaxis, internal fixation implantation were risk factors for infections after arthroscopic rotator cuff repair. Multivariate Logistic regression analysis showed male(OR=14.227), age≥65 years(OR=34.313), operation time≥2 h (OR=15.616), without antibiotic prophylaxis(OR=4.891), and internal fixation implantation(OR=5.103) were major risk factors for infection after arthroscopic rotator cuff repair(P<0.05).@*CONCLUSION@#Male, age≥65 years, operation time≥2 h, without antibiotic prophylaxis and internal fixation implantation were independent risk factors for infection after arthroscopic rotator cuff repair. Early diagnosis and timely treatment should be carried out to reduce the incidence of infection.

Mechanism of gigantol in transmembrane transport in human lens epithelial cells / 中国中药杂志

Gigantol is a phenolic component of precious Chinese medicine Dendrobii Caulis, which has many pharmacological activities such as prevent tumor and diabetic cataract. This paper aimed to investigate the molecular mechanism of gigantol in transmembrane transport in human lens epithelial cells(HLECs). Immortalized HLECs were cultured in vitro and inoculated in the laser scanning confocal microscopy(LSCM) medium at 5 000 cells/mL. The fluorescence distribution and intensity of gigantol marked by fluorescence in HLECs were observed by LSCM, and the absorption and distribution of gigantol were expressed as fluorescence intensity. The transmembrane transport process of gigantol in HLECs were monitored. The effects of time, temperature, concentration, transport inhibitors, and different cell lines on the transmembrane absorption and transport of gigantol were compared. HLECs were inoculated on climbing plates of 6-well culture plates, and the ultrastructure of HLECs was detected by atomic force microscopy(AFM) during the transmembrane absorption of non-fluorescent labeled gigantol. The results showed that the transmembrane absorption of gigantol was in time and concentration-dependent manners, which was also able to specifically target HLECs. Energy and carrier transport inhibitors reduced gigantol absorption by HLECs. During transmembrane process of gigantol, the membrane surface of HLECs became rougher and presented different degrees of pits, indicating that the transmembrane transport of gigantol was achieved by active absorption of energy and carrier-mediated endocytosis.

Clinical Significance of Thrombospondin Type 1 Domain-Containing 7A and Neural Epidermal Growth Factor-Like 1 Protein in M-Type Phospholipase A2 Receptor-Negative Membranous Nephropathy / 中国医学科学院学报

Objective To investigate the clinical significance of thrombospondin type 1 domain-containing 7A (THSD7A) and neural epidermal growth factor-like 1 protein (NELL1) in phospholipase A2 receptor (PLA2R)-negative membranous nephropathy (MN). Methods A total of 116 PLA2R-negative MN patients treated in Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University from 2014 to 2021 were enrolled in this study.Immunohistochemistry was employed to detect THSD7A and NELL1 in the renal tissue.The pathological characteristics,treatment,and prognosis were compared between positive and negative groups. Results The 116 PLA2R-negative MN patients included 23 THSD7A-positive patients and 9 NELL1-positive patients.One patient was tested positive for both proteins.The THSD7A-positive group showed higher positive rate of IgG4 (P=0.010),more obvious glomerular basement membrane (GBM) thickening (P=0.034),and higher proportion of stage Ⅱ MN and lower proportion of stage I MN (P=0.002) than the THSD7A-negative group.The NELL1-positive group had lower positive rates of C1q and IgG2 (P=0.029,P=0.001),less obvious GBM thickening (P<0.001),more extensive inflammatory cell infiltration (P=0.033),lower proportion of deposits on multi-locations (P=0.001),and lower proportion of atypical MN (P=0.010) than the NELL1-negative group.One patient with THSD7A-positive MN was diagnosed with colon cancer,while none of the NELL1-positive patients had malignancy.Survival analysis suggested that THSD7A-positive MN had worse composite remission (either complete remission or partial remission) of nephrotic syndrome than the negative group (P=0.016),whereas NELL1-positive MN exhibited better composite remission of nephrotic syndrome than the negative group (P=0.015).The MN patients only positive for NELL1 showed better composite remission of nephrotic syndrome than the MN patients only positive for THSD7A (P<0.001). Conclusions THSD7A- and NELL1-positive MN is more likely to be primary MN,and there is no significant malignancy indication.However,it might have a predictive value for the prognosis of MN.

Expression and Detection Value of 6 Chlamydia Trachomatis Protein Antibodies in Tubal Factor Infertility / 中山大学学报(医学科学版)

ObjectiveTo further study the pathogenic role of different types of Chlamydia trachomatis （CT） proteins in tubal factor infertility， evaluate the clinical detection value of Chlamydia trachomatis protein antibody in predicting tubal factor infertility. MethodsA total of 58 cases of tubal factor infertility （TFI）， 41 cases of fertile controls （FC） and 18 cases of infertile controls （IFC） were included. For serum detection， first， CT-IgG ELISA kit was used to detect the expression of CT-IgG in serum of three groups of people； then， 6 kinds of Chlamydia trachomatis proteins were expressed and purified in the early stage to establish the antibody test for these proteins， and ELISA detection method was used to detect the expression of their antibodies in the serum of TFI group， FC group and IFC group， respectively； and finally， the antibody OD value of the 6 kinds of Chlamydia trachomatis proteins in the three groups of subjects were statistically described， and CT-IgG was used as the reference standard to draw the receiver operating characteristic curve （ROC curve） of each CT antibody. The Youden Index determines the cutoff value for each antibody. Taking TFI as the reference class， two disordered multiple classification logistic regression models were established with the FC and IFC groups， respectively； and the reference class was used to explore the value of various antibodies and age in predicting TFI， FC and IFC of Chlamydia trachomatis. The back-off method was used to screen the variables. ResultsThe OD value of CT376 antibody in the TFI group was higher than that in the FC group （0.86 vs. 0.60， P=0.026）. The CT376 antibody OD value in the TFI group was higher than that in the IFC group （0.86 vs. 0.64， P=0.026）. The CT443 antibody OD value in the IFC group was higher than that in the TFI group （0.59 vs. 0.34， P=0.036） and higher than that in the FC group （0.59 vs. 0.30， P=0.02）. The multiple classification logistic regression analysis established between TFI and FC showed that CT-IgG ［P<0.001， OR=0.084， 95%CI （0.025， 0.284）］， CT376 antibody ［P=0.068， OR=0.359， 95%CI （0.120， 1.078）］. CT-IgG is an independent risk factor for tubal infertility， and CT376 antibody cannot be an independent risk factor for tubal infertility. The multiple classification logistic regression analysis established between TFI and IFC showed that among infertile patients， CT-IgG ［P<0.05， OR=0.194， 95%CI （0.046， 0.817）］， CT376 antibody ［P<0.05， OR=0.176， 95%CI （0.038， 0.818）］ and CT381 antibody ［P<0.05， OR=0.112， 95%CI （ 0.016， 0.796）］ were independent risk factors for tubal infertility. ConclusionThe expression of CT376 antibody in tubal infertility patients is higher than that in fertile and infertile controls， suggesting that CT-induced tubal factor infertility may be related to CT376. CT-IgG， and CT376 antibodies are meaningful in predicting CT-induced tubal factor infertility.

Clinical Value of Translocator Protein Gene in Evaluating the Efficacy of FLT3-ITD/DNMT3A R882 Double-Mutated Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML).@*METHODS@#Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation).@*RESULTS@#The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011).@*CONCLUSION@#TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.

miR-142-3p alleviates house dust mite induced airway inflammation among children / 中国学校卫生

Objective@#To investigate the role of miR-142-3p in alleviation of house dust mite induced allergic airway inflammation among children, so as to provide insights into unraveling the pathogenesis of allergic airway inflammation.@*Methods@#Serum samples were collected from 15 patients with house dust mite induced allergic asthma and 15 healthy children in Jiangnan University Medical Center from September to November 2022, and serum miR-142-3p expression was quantified using a fluorescent quantitative real time PCR (qPCR) assay. The levels of interleukin 6 (IL 6) and tumor necrosis factor α (TNF α) were measured in the cell culture supernatant using enzyme linked immunosorbent assay (ELISA), and the expression of high mobility group box 1 (HMGB1) was detected at transcriptional and translational lvels using qPCR and Western blotting assays. The negative regulation of the HMGB1 gene by miR 142 3p was identified using a dual luciferase gene reporter assay, and the expression of downstream regulatory proteins was determined in human normal lung epithelial cells (BEAS 2B) cells transfected with miR 142 3p using Western blotting. In addition, female C57BL/6 mice at ages of 6-8 weeks were randomly assigned to the phosphate buffer saline (PBS) group, house dust mite sensitized airway inflammation group and house dust mite sensitized airway inflammation + miR 142 3p intervention group. Mouse airway inflammation was evaluated using hematoxylin eosin staining, and the expression of inflammatory cells and inflammatory cytokines were detected in mouse bronchoalveolar lavage fluid (BALF) using Giemsa staining and ELISA.@*Results@#Lower serum miR-142-3p expression was quantified among children with house dust mite induced allergic asthma than among healthy controls (1.33±0.21 vs. 4.74±0.62, t=5.22, P <0.05). Stimulation with dermatophagoides farinae extract (DFE) resulted in a reduction in miR-142-3p expression in BEAS-2B cells (0.82±0.25), while transfection with miR-142-3p mimics resulted in a rise in miR-142-3p expression in BEAS-2B cells (0.55±0.14)( t=3.31, 3.94, P <0.05). Pre treatment with miR-142-3p reduced the expression of IL 6(2.25±0.46)and TNF α(6.58±1.95) ( t=4.86, 3.38, P <0.05) in BEAS 2B cells stimulated with DFE, and treatment with miR-142-3p mimics resulted in a reduction in TLR4 and NF-κB expression in BEAS-2B cells via negative regulation of the HMGB1 expression. In addition, treatment with miR-142-3p was found to alleviate inflammatory cell infiltration in lung tissues of house dust mite sensitized mice, and results in a reduction in interleukin 4 (IL-4)[(107.60±10.43)pg/mL], interleukin 5 (IL 5)[(95.78±13.14)pg/mL] and HMGB1[(2.52±0.87)pg/mL] expression in BALF ( t=10.32, 7.29, 2.90, P <0.05).@*Conclusion@#miR-142-3p alleviates house dust mite induced allergic airway inflammation among children via negative regulation of the HMGB1/TLR4/NF-κB pathway.