CHINA PH ARMACY Volume 33，Number 12，June 30，2022 Semimonthly Table of Contents Construction of total q uality managemen t system of clinica l comprehens ive evaluation of drugs in China / 中国药房

OBJECTIVE To provide reference for scientifi c and standardized development of clinical comprehensive evaluation of drugs in China. METHODS Guided by the theory of total quality management （TQM），drawing lessons from the successful experience of the British and German conducting evaluation ，combining with plan-do-check-act cycle and other quality management methods and tools ，drug clinical comprehensive evaluation of total quality management system was constructed in accordance with the requirements for our country related policy and local practice. RESULTS & CONCLUSIONS To construct total quality management system of clinical comprehensive evaluation of drugs in China from 5 aspects of organization system ，management process，assessment system ，evaluation and supervision platform ，support and guarantee mechanism. The organization system included national ，provincial and medical institutions ；management process should focus on the key links in the 3 stages of theme selection，evaluation and implementation ，and result transformation and application ；assessment system ，evaluation and supervision platform，support and guarantee mechanism should be established together so as to further improve the scientificity ，rationality， practicality and standardization of total quality management of clinical comprehensive evaluation of drugs. The development of total quality management is an effective starting point to promote the continual improvement of the drug clinical comprehensive evaluation；relevant government departments and the implementation of evaluation of medical institutions should further set up quality management consciousness ，establish report quality feedback mechanism and the results co-constructing and sharing mechanism and strengthen professional personnel training and innovation synergy regulation mode to ensure that the authenticity and reliability of evaluation results.

Contrast-enhanced ultrasound as a valuable imaging modality for characterizing testicular lesions / 亚洲男科学杂志(英文版)

Contrast-enhanced ultrasound (CEUS) is a new form of ultrasound (US) that can dynamically display microvessels in a highly sensitive manner. The purpose of this study was to investigate the efficacy of CEUS for characterizing testicular lesions in comparison with conventional US. Forty-seven patients with testicular lesions were enrolled. The histopathology results revealed that 31 cases were neoplastic (11 cases of seminomas, 8 nonseminomatous germ cell tumors, 8 lymphomas, 2 Leydig cell tumors, and 2 nonspecific tumors), and 16 cases were nonneoplastic (8 cases of infarctions, 3 epidermoid cysts, and 5 inflammation). The indicators of shallow lobulated morphology and cystic-solid echogenicity on conventional US were suggestive of germ cell tumors. More indicators on CEUS were found to be useful for characterizing testicular lesions. All the neoplastic lesions showed hyperenhancement on CEUS. Moreover, germ cell tumors presented with heterogeneous enhancement (73.7%, 14/19), a twisted blood vessel pattern, rapid wash-in and wash-out, and peripheral rim hyperenhancement signs. Lymphoma was characterized by nonbranching linear vessel patterns (87.5%, 7/8), rapid wash-in and slow wash-out. In nonneoplastic lesions, infarction and epidermoid cysts showed no enhancement, and abscesses were observed with marginal irregular enhancement. The sensitivity, specificity, and accuracy of CEUS for differentiating between neoplastic and nonneoplastic lesions were 100%, 93.8%, and 97.9%, respectively, and these values were higher than those for conventional US (90.3%, 62.5%, and 80.9%, respectively). CEUS can sensitively reflect the microvascular perfusion in testicular lesions and offers high accuracy for characterizing them.

T lymphocyte subsets combined with inflammatory indicators for auxiliary diagnosis and prognosis evaluation of sepsis / 中华预防医学杂志

Objective: To explore the application value of T lymphocyte subsets combined with procalcitonin (PCT), C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR) and white blood cell count (WBC) in the auxiliary diagnosis and prognosis evaluation of sepsis. Methods: In a retrospective study, seventy-two patients with sepsis diagnosed and treated in Tianjin First Central Hospital from June 2018 to April 2021 were selected as the research objects, and included in the sepsis group were 46 males and 26 females, aged 68 (57.3, 80.3) years. In addition, 111 patients with local infection admitted to hospital during the same period were included in the local infection group, including 62 males and 49 females, aged 68 (51, 77) years. Sepsis patients were divided into survival group (43 cases) and death group (29 cases) according to the 28-day outcome. CD3+, CD4+, CD8+, CD4+/CD8+ ratio were detected by flow cytometry within 24 h after admission, PCT was detected by ELISA, CRP was detected by immunoturbidimetry, blood routine examination, blood lactic acid (Lac) and oxygen partial pressure (PO2) were detected by instrumental method. Multivariate Logistic regression analysis was used to evaluate the correlation between each indicator and sepsis, and receiver operating characteristic curve (ROC) was drawn to evaluate the diagnostic value of each indicator for sepsis. Multivariate Logistic regression analysis and Kaplan Meier survival analysis were used to evaluate the prognostic value of each index for patients with sepsis. Results: Peripheral blood CD3+, CD4+, CD8+, CD4+/CD8+ ratio and PLT in sepsis group were significantly lower than those in local infection group(Z=-8.184,P<0.001;Z=-7.210,P<0.001;Z=-5.936,P<0.001;Z=-2.700,P=0.007;Z=-6.381,P<0.001); PCT, CRP, NLR and Lac levels were significantly higher than those in local infection group(Z=-8.262,P<0.001;Z=-3.094,P=0.002;Z=-9.004,P<0.001;Z=-4.770,P<0.001). Multivariate Logistic regression model showed that PCT, NLR, CD3+, CD8+, CD4+/CD8+ were independent risk factors for sepsis. According to ROC curve analysis, AUC of sepsis patients diagnosed by each indicator were 0.862, 0.894, 0.858, 0.760 and 0.618, respectively. The cut-off values were 3.075 ng/ml, 10.715, 44.935×109/L, 27.463×109/L and 0.750, respectively. The NLR sensitivity was 80.6%, and the CD3+ specificity was 94.6%. The AUC of combined detection of PCT and NLR was 0.947, sensitivity was 87.5% and specificity was 91.9%. The combined detection AUC of PCT, NLR, CD3+, CD4+/CD8+ was 0.958, the sensitivity and specificity were 90.3% and 91.0% respectively(P<0.001). PCT and Lac in death group were significantly higher than those in survival group(Z=-2.302,P=0.021;Z=-3.095,P=0.002);Peripheral blood CD4+/CD8+ levels were significantly lower than those in survival group(Z=-3.691,P<0.001),Multivariate Logistic regression model showed that CD4+/CD8+ ratio was an independent risk factor for 28 d mortality in patients with sepsis (P<0.001). The ROC curve showed that the AUC was 0.758, and the Youden index reached the maximum when the cut-off value was 1.27, the sensitivity and specificity were 79.3% and 60.5%, respectively. Compared with patients with CD4+/CD8+ ≥1.27, 28-day mortality was significantly increased in patients with CD4+/CD8+<1.27 (P=0.032). Conclusion: The combined detection of PCT, NLR, CD3+ and CD4+/CD8+ can improve the auxiliary diagnostic efficiency of sepsis, and the ratio of CD4+/CD8+ in peripheral blood may have certain predictive value for the prognosis of sepsis.

Characteristics of neuralgia in patients with Fabry disease in China / 中华神经科杂志

Objective:To summarize the characteristics of neuralgia in Fabry disease and explore the effects of genders and alpha-galactosidase A (GLA) gene mutation types on neuralgia.Methods:Questionnaires and Brief Pain Inventory evaluations were conducted on the recruited patients diagnosed as Fabry disease in Department of Neurology, Peking University First Hospital from January 2001 to April 2020. The characteristics of the neuralgia were summarized, and the portrait of neuralgia between male and female patients, and the patient groups carrying truncated mutations and non-truncated mutations of GLA gene was compared.Results:A total of 93 patients with Fabry disease were enrolled. The incidence of neuralgia was 91.4% (85/93),and the average onset age of pain was 9 years. The average remission age was 20 years with the remission incidence of 22.8% (18/79). Pain attack on extremities [96.5%(82/85)] was the most common form. The neuralgia relieving rate of male patients [17.5%(11/63)] was lower than that of females (7/16, χ2=5.01, P=0.025).Brief Pain Inventory scores showed that the degree of most severe pain attack within 24 hours of male patients (4.16±3.20) was higher than that of females (2.07±2.02, t=3.03, P=0.004),and the impact of pain on daily life [male 4 (7) vs female 0 (4), Z=-2.33, P=0.020], walking ability [male 5 (8) vs female 0 (2), Z=-2.87, P=0.004], daily work [male 5 (8) vs female 0 (2), Z=-3.10, P=0.002], relationship [male 2 (6) vs female 0 (3), Z=-2.67, P=0.008] and interests [male 4 (8) vs female 0 (3), Z=-2.81, P=0.005] of male patients was also higher than female patients. The truncated mutation group [1 (2)] only showed higher score on the current pain level than the non-truncated mutation group [0(0), Z=-2.89, P=0.003]. Conclusions:The neuralgia in Chinese patients with Fabry disease showed high incidence and early onset. Male patients presented more severe pain than female which led to a greater impact on life, while the type of GLA gene mutation had less impact on neuralgia.

Effect of enteral nutrition support on hematological complications in children with malignant solid tumor during chemotherapy / 中华全科医师杂志

Objective:To investigate the effect of enteral nutrition on hematological complications in children with malignant solid tumors during chemotherapy.Methods:A total of 103 children with malignant solid tumor admitted to our hospital from March 2020 to December 2020 were enrolled in the study. The children were randomly divided into enteral nutrition group ( n=51) and control group ( n=52). Children in enteral nutrition group were given enteral nutrition support on the basis of routine diet, while children in control group were only given routine diet. The levels of leukocytes, neutrophils, hemoglobin and platelets in peripheral blood of children during chemotherapy were analyzed. The incidence of infection and the transfusion of red blood cells and platelets after chemotherapy were documented and compared between two groups. Results:The levels of white blood cells, neutrophils, hemoglobin and platelets before chemotherapy were significantly higher than those after chemotherapy both in enteral nutrition group ( Z=-5.91, -5.59, -5.54, -5.66, all P<0.05) and in control group ( Z=-6.14, -5.84, -5.75, -4.75, all P<0.05). The overall hemoglobin levels in enteral nutrition group before and after chemotherapy was significantly higher than those in control group ( t=5.68, 5.62, P<0.05), and there were no significant differences in the levels of white blood cells, neutrophils and platelets between the two groups before chemotherapy ( Z=-0.71, -0.12, -1.29, all P>0.05) and after chemotherapy ( Z=-0.39, -0.86, -0.94, all P>0.05). Compared with the control group, the degree of anemia during chemotherapy was significantly improved in enteral nutrition group (χ2=10.45,6.12, all P<0.05), but there was no significant difference in the reduction degree of white blood cells, neutrophils and platelets between the two groups (before chemotherapy: χ2=1.17, 0.10, 0.49; after chemotherapy: χ2=0.18, 1.10, 0.97, all P>0.05). The number of children receiving red blood cell transfusion in enteral nutrition group was significantly lower than that in control group (χ2=14.06, P<0.05), and there was no significant difference in the number of children with infection and platelet transfusion between the two groups (χ2=1.20, 0.29, all P>0.05).There was no significant difference in the duration of neutrophil deficiency between enteral nutrition group and control group ( t=-1.75, P>0.05). Conclusion:Enteral nutrition support can significantly improve the hemoglobin level in children during chemotherapy, effectively alleviate the severity of anemia, and reduce the incidence of red blood cell transfusion after chemotherapy, which has high clinical application value.

Preoperative Nomogram prediction model for lymph node metastasis in patients with renal cell carcinoma / 中华泌尿外科杂志

Objective:To identify preoperative clinical predictors of positive lymph nodes in patients with renal cell carcinoma (RCC)and provide a preoperative predictive model.Methods:The data of 173 RCC patients who underwent either retroperitoneal lymph node dissection or biopsy at a single institution from January 2016 to December 2020 were retrospectively analyzed. There were 109 males and 64 females, with an average age of (53.29±13.58) years, median tumor diameter of 70 (23-150) mm, 68 patients with local symptoms, 24 patients with systemic symptoms, and 56 patients with ECOG score ≥1. There were 96 patients with tumor pseudocapsule, 23 patients with renal vein or inferior vena cava tumor thrombus, 114 patients in stage T 1-2, 59 patients in stage T 3-4, 22 patients with distant metastasis and 88 patients with lymph node metastasis by preoperative imaging examination. Univariate analysis was performed by Mann-Whitney U test or Chi-square test, and multivariate logistic regression analysis was used to determine preoperative predictors of pathologic lymph node positivity. The significant variables were then included in a novel Nomogram to predict the probability of lymph node invasion.C-index and Bootstrap self-sampling methods were used to evaluate the discrimination and consistency of the model. Results:Of the 173 patients, 49(28.32%)and 124(71.68%)had pN 1 and pN 0 disease, respectively. Among 88 patients with suspected lymph node involvement (cN 1) assessed by preoperative imaging, only 47.73%(42/88) were confirmed to be pathologically positive. However, 8.24% (7/85) of the 85 patients with negative lymph nodes (cN 0) assessed by preoperative imaging were pathologically positive. Age, ECOG score, symptoms at presentation, tumor pseudocapsule, metastasis at diagnosis, clinical tumor stage, clinical nodal status, clinical nodal size, D-dimer, lactate dehydrogenase, microscopic hematuria were significant in the univariate analysis ( P<0.05). On multivariable analyses, the most informative independent predictors were age, clinical tumor stage, clinical nodal status, clinical nodal size and microscopic hematuria ( P<0.05). A Nomogram with good performance was developed to predict the probability of lymph node metastasis. The C-index of the model was 0.954, the calibration curve of forecasting curve with the ideal curve fit was good, indicating that the model has a good consistency. Conclusions:Younger age, microscopic hematuria, suspected lymph node involvement in imaging, larger lymph node diameter and higher T stage were independent risk factors for renal cell carcinoma with lymph node metastasis. The Nomogram based on the above factors has good identification and calibration ability, which can help predict the probability of lymph node metastasis of renal cell carcinoma before surgery.

Meta-analysis of the correlation between growth and thyroid volume in children / 中华地方病学杂志

Objective:To systematically evaluate the relationship between growth and thyroid volume (Tvol).Methods:Chinese and English papers were searched in CNKI, Wanfang Data, VIP Database, PubMed, EMbase, Springerlink, Medline database, articles on the correlation between Tvol and growth in children published from the establishment of these databases to October 2021 were collected. Meta-analysis was conducted with R language 4.0. I2 and Q test were used for heterogeneity test. According to the heterogeneity test results, the fixed effect model or random effect model was selected, and sensitivity analysis was conducted. Egger's method was used to test publication bias. Results:A total of 17 papers were incorporated in this study, including 11 Chinese papers and 6 English papers. The correlation between body surface area (BSA) and Tvol was the strongest[estimated effect value ( COR) = 0.44, 95% confidence interval ( CI): 0.39 - 0.50], followed by weight ( COR = 0.39), height ( COR = 0.37) and age ( COR = 0.29). Sensitivity analysis showed that the estimated effects COR were all within 95% CI of the total effects after deleting any paper, which indicated that the results of Meta-analysis were reliable. Egger's method result showed P > 0.05, indicating that there was no obvious publication bias in this study. Conclusion:Age, height, weight and BSA all have effects on Tvol, among which BSA has the greatest effect.

Analysis on the diagnosis of 47 cases of Kala-azar in Gansu Province / 中华地方病学杂志

Objective:To learn about the diagnosis of Kala-azar in Gansu Province, and to provide a basis for formulating corresponding prevention and control measures.Methods:The data (age, gender, onset time, diagnosis time, diagnosis unit, etc.) of Kala-azar cases in Gansu Province from January to December 2018 were collected from the China Disease Prevention and Control Information System. At the same time, a case report questionnaire was designed to collect information such as the initial diagnosis unit and initial diagnosis results; a diagnosis and treatment questionnaire of medical institutions was designed to investigate the knowledge of diagnosis and treatment of Kala-azar (main epidemic areas, main symptoms, common detection methods, main therapeutic drugs and drug use methods) among doctors in county and township hospitals, and the pass rate and awareness rate were calculated.Results:A total of 47 Kala-azar cases were included, with an average age of 17 years. Among them, men accounted for 57.45% (27/47) and women accounted for 42.55% (20/47). Among the initial diagnosis hospitals, the proportions of provincial, municipal, county and township hospitals were 2.13% (1/47), 12.77% (6/47), 42.55% (20/47) and 42.55% (20/47), respectively; among the hospitals with confirmed cases, provincial, municipal, county and township hospitals accounted for 48.94% (23/47), 31.91% (15/47), 19.15% (9/47) and 0 (0/47), respectively. The shortest time from initial diagnosis to diagnosis of the 47 cases was 1 day; the longest was 124 days, with an average of 27 days. A total of 96 valid questionnaires were collected from doctors in county and township hospitals, of which 30 scored 60 points or above, and the pass rate was 31.25% (30/96). Among the five surveys on diagnosis and treatment knowledge of Kala-azar, doctors in county and township hospitals had the highest awareness rate of "main therapeutic drugs", which was 77.08% (74/96), and there was significant difference (χ 2 = 9.86, P = 0.002) between doctors in the two-level hospitals [90.00% (45/50), 63.04% (29/46)]. The awareness rate of "main symptoms" was the lowest, which was 25.00% (24/96), and there was significant difference (χ 2 = 4.51, P = 0.034) between doctors in the two-level hospitals [34.00% (17/50), 15.22% (7/46)]. Conclusions:The awareness rate of diagnosis and treatment knowledge of Kala-azar among doctors in county and township hospitals in Gansu Province is low, and their diagnostic ability is weak. It is recommended to strengthen the training of clinicians, improve the timeliness of diagnosis, and achieve early diagnosis, early report and early treatment of Kala-azar.

Species identification and phylogenetic analysis of canine Leishmania in Diebu County, Gansu Province / 中华地方病学杂志

Objective:To investigate the species types and phylogenetic relationship of canine Leishmania in Diebu County, Gansu Province, so as to provide a basis for exploring new methods of prevention and control of canine visceral leishmaniasis. Methods:DNA was extracted from blood samples of eight asymptomatic Leishmania-infected dogs in Luoda administrative village in Diebu County, Gansu Province. Ribosomal internal transcribed spacer 1 (ITS-1) gene fragments were amplified and isolated by PCR, and then the amplified target fragments were sequenced. The MEGA 7.0 software was used for multiple sequence alignment, and a phylogenetic tree was constructed by neighbor-joining method to analyze the phylogenetic relationship of canine Leishmania in Diebu County, Gansu Province. Results:Fragments of about 320 bp corresponding in size to the target sequence ITS-1 were isolated from all of the eight asymptomatic Leishmania-infected dogs blood samples. ITS-1 sequence alignment showed that the sequence homology between 8 samples and Leishmania infantum MG969403, MN648755 strains was 99.1% - 100.0%; phylogenetic tree showed that all 8 samples were clustered into one branch with Leishmania infantum. Conclusion:Leishmania infantum is identified from all of the eight asymptomatic Leishmania-infected dogs blood samples in Diebu County, Gansu Province.

Application value of Da Vinci robotic transanal minimally invasive surgery for local resection of rectal neoplasms / 中华消化外科杂志

Objective:To investigate the application value of Da Vinci robotic transanal minimally invasive surgery (R-TAMIS) for local resection of rectal neoplasms.Methods:The retros-pective and descriptive study was conducted. The clinicopathological data of 7 rectal neoplasms patients undergoing R-TAMIS in Daping Hospital of Army Medical University from June 2017 to March 2021 were collected. There were 3 males and 4 females, aged (60±7)years. Observation indicators: (1) intraoperative situations; (2) postoperative recovery; (3) postoperative histopatholo-gical examinations; (4) follow-up. Follow-up was conducted using telephone interview or outpatient examination to detect readmission of patients within postoperative 30 days, tumor recurrence and metastasis and survival of patients. Follow-up was performed at postoperative 1, 3, 6 months and once every 6 months thereafter up to April 2021. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Intraoperative situations. All the 7 patients underwent R-TAMIS successfully without conversion to laparotomy or laparoscopic surgery. Of the 7 patients, 2 cases underwent full-thickness rectal resection and 5 cases underwent submucosal dissection of tumor. The rectal wounds were not sutured in 2 cases because of large lesions, and the rectal wounds were sutured with synthetic sutures in 5 cases after resection of lesions. Transanal drainage tube was placed in 2 cases and not in 5 cases. The volume of intra-operative blood loss of the 7 patients was 15(range, 2?50)mL. The total operation time of the 7 patients was (91.4±18.4)minutes, including (19.1±2.3)minutes for transanal platform placement and Da Vinci robotic surgical system installation, and (72.3±16.6)minutes for operation. There was no intraoperative complication such as urethral injury. (2) Postoperative recovery. All the 7 patients started water drinking and out-of-bed activities at postoperative day 1 and liquid food intake at postoperative day 2. The time to postoperative first flatus of the 7 patients was 1(range, 1?3)days. The two cases with transanal drainage underwent removing of transanal drainage at postoperative day 2. There was no postoperative complication and the duration of postoperative hospital stay of the 7 patients was 3(range, 3?9)days. (3) Postoperative histopathological examinations. Of the 7 patients, 3 cases had villous adenoma, 2 cases had villous adenoma combined with high grade intraepithelial neoplasia, local canceration and tumor invasion into submucosa (stage SM1), 1 case had villous adenoma combined with high grade intraepithelial neoplasia, local canceration and tumor localized in the inner mucosa (stage Tis) and 1 case had moderately differentiated adeno-carcinoma with tumor invasion into superficial muscle layer (stage T2). All the 7 patients had negative surgical margins with none of tumor cell remained in the base. (4) Follow-up. All the 7 patients were followed up for 18(range, 1?42)months. One of the 7 patients showed rectal adenocarcinoma with tumor invasion into superficial muscle layer by the postoperative histopathological examina-tion and was recommended for remedial radical surgery. The patient refused further surgery and underwent 3 courses of oral capecitabine chemotherapy. The other 6 patients did not receive postoperative chemotherapy. None of 7 patients underwent readmission within postoperative 30 days, and no patient had tumor local recurrence, distant metastasis or death during the follow-up.Conclusion:R-TAMIS for local resection of rectal neoplasms is safe and feasible for patients with rectal adenoma and early rectal cancer, with reliable short-term efficacy and short-term oncological efficacy.

Strengthening the prevention and treatment of hungry bone syndrome, parathyroid hyperfunction and hyperparathyroidism of thyroid cancer patients after thyroidectomy / 中华内分泌外科杂志

Differentiated thyroid cancer is one of the most common endocrine malignant tumors, and thyroidectomy is its basic treatment measures. Insufficient attention is paid to its postoperative bone hungry syndrome and parathyroid hyperfunction or hyperparathyroidism, which will seriously affect the patient’s life quality and prognosis. This paper will explore the etiology, dangers, diagnosis, prevention, and treatment for hungry bone syndrome, parathyroid hyperfunction and hyperparathyroidism of thyroid cancer patients after thyroidectomy.

Integrating 16S sequencing and metabolomics study on anti-rheumatic mechanisms against collagen-induced arthritis of Wantong Jingu Tablet / 中国天然药物

Wantong Jingu Tablet (WJT), a mixture of traditional Chinese medicine, was reported to relieve the symptoms of rheumatoid arthritis (RA), but its pharmacological mechanism was not completely understood. The aim of this study was to investigate the therapeutic mechanisms of WJT for RA in vivo. The effects of WJT on joint pathology, as well as the levels of Bax, Bcl-2, caspase-3, cleaved-caspase-3, ERK1/2, pERK1/2, TNF-α, IL-1β, and IL-6 were measured using collagen-induced arthritis (CIA) rats. The intestinal flora composition and the metabolites alteration were analyzed by 16S rDNA sequencing and metabolomics method, respectively. We found that WJT ameliorated the severity of the CIA rats which might be mediated by inducing apoptosis, inactivating the MEK/ERK signals and reducing the production of pro-inflammatory cytokines. WJT, in part, relieved the gut microbiota dysbiosis, especially bacterial phylum Bacteroidetes, Tenericutes and Deferribacteres, as well as bacterial genus Vibrio, Macrococcus and Vagococcus. 3'-N-debenzoyl-2'-deoxytaxol, tubulysin B, and magnoline were significantly associated with the specific genera. We identified serotonin, glutathione disulfide, N-acetylneuraminic acid, naphthalene and thromboxane B2 as targeted molecules via metabolomics. Our findings contributed to the understanding of RA pathogenesis, and WJT played essential roles in gut microbiota health and metabolite modulation in the CIA rats.

Diethylhexyl phthalate induces anxiety-like behavior and learning and memory impairment in mice probably by damaging blood-brain barrier / 南方医科大学学报

OBJECTIVE@#To investigate the effects of diethylhexyl phthalate (DEHP) exposure on anxiety-like behaviors and learning and memory ability in mice and explore the underlying mechanism.@*METHODS@#Forty male ICR mice were randomized equally into control group (0 mg/kg) and 10, 50 and 100 mg/kg DEHP exposure groups, in which the mice were exposed to DEHP at the indicated doses by gavage for 4 weeks. After the treatments, the mice were assessed for behavioral changes using open filed test, elevated plus-maze and Morris water maze test. Brain tissues were collected from the mice for determination of malondialdehyde (MDA) content, pathologies and expressions of ZO-1 and occludin in the hippocampus.@*RESULTS@#Compared with the control group, the mice with DEHP exposure for 4 weeks exhibited no significant body weight change (P>0.05) but presented with obvious behavioral changes, manifested by reduced movement distance (P < 0.05) and time spent in the center of the open field (P < 0.05), reduced movement distance (P < 0.05) and time spent in the open arm of the elevated maze (P < 0.05), significantly increased latency of searching for the platform (P < 0.05), and decreased frequency of crossing the platform (P < 0.05). HE staining showed obvious vertebral cell death in the hippocampal CA1 to CA3 regions of the mice with DEHP exposure. The exposed mice showed significantly increased MDA content and decreased expressions of ZO-1 and occludin at both the mRNA and protein levels in the hippocampus (P < 0.05 or 0.01). Multivariate linear regression analysis suggested a close correlation between anxiety-like behaviors and learning and memory abilities in DEHP-exposed mice.@*CONCLUSION@#DEHP exposure may cause damages of the blood-brain barrier and the pyramidal cells in the hippocampus of mice, thereby inducing anxiety-like behaviors and learning and memory impairment.

Clinical characteristics of 18 children with chronic nonbacterial osteomyelitis / 中华儿科杂志

Objective: To investigate the clinical features of children with chronic nonbacterial osteomyelitis (CNO), and raise awareness among clinicians. Methods: In this retrospective study, 18 patients with CNO who were diagnosed in Children's Hospital of Fudan University from January 2015 to December 2021 were included. Results: Eighteen children with CNO (12 males, 6 females) were identified. Their age at onset was 9 (5, 11) years, the delay in diagnosis was 2 (1, 6) months, and follow-up-was 17 (8, 34) months. The most common symptoms were fever in 14 children, as well as bone pain and (or) arthralgia in 14 children. In terms of laboratory results, normal white blood cell counts were observed at onset in 17 patients; increased erythrocyte sedimentation rate (ESR) in all patients; increased C reactive protein (CRP) over the normal value in 14 patients. Of the 18 patients, 2 had positive antinuclear antibodies, while none had positive human leukocyte antigen-B27 or rheumatoid factor. Imaging examination revealed that all the patients had symmetrical and multifocal skeletal lesions. The number of structural lesions detected by imaging investigation was 8 (6, 11). The most frequently affected bones were tibia in 18 patients and femur in 17 patients. Bone biopsy was conducted in 14 patients and acute or chronic osteomyelitis manifested with inflammatory cells infiltration were detected. Magnetic resonance imaging (MRI) found bone lesions in all the patients and bone scintigraphy were positive in 13 patients. All the patients were treated with nonsteroidal anti-inflammatory drugs, among whom 10 cases also treated with oral glucocorticoids, 9 cases with traditional disease modifying anti-rheumatic drugs, 8 cases with bisphosphonates and 6 cases with tumor necrosis factor inhibitors. The pediatric chronic nonbacterial osteomyelitis disease activity score, increased by 70% or more in 13 patients within the initial 6-month follow-up. Conclusions: The clinical manifestations of CNO are lack of specificity. The first symptom of CNO is fever, with or without bone pain and (or) arthralgia, with normal peripheral blood leukocytes, elevated CRP and (or) ESR. Whole body bone scanning combined with MRI can early detect osteomyelitis at subclinical sites, and improve the diagnostic rate of CNO.

Effect of Body Mass Index on the Prognosis of Mantle Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To explore the correlation between different body mass index (BMI) and prognosis of mantle cell lymphoma (MCL).@*METHODS@#The clinical characteristics and biological indices of 108 patients with MCL treated in Fujian Medical University Union Hospital were retrospectively analyzed, and the effects of different BMI on overall survival (OS) and progression-free survival (PFS) were analyzed. The correlation between BMI and B symptoms, LDH and Ki-67 was further observed. Furthermore，the differences of BMI between Autologous peripheral blood stem cell transplantation(Auto-PBSCT) and conventional chemotherapy groups were explored.@*RESULTS@#Among 108 patients, the median age at diagnosis was 59（25-79） years old, and the male to female ratio was 4.4∶1. 88.89% of patients with Ann Arbor staging III-IV, 63.89% with bone marrow involvement, and 49.07% with splenic infiltration. Patients with BMI ≥ 24 kg/m2 were divided into two groups: the high BMI group and the low BMI group. The 5-year PFS and OS of patients in the low BMI group were 31.9% and 47.0%, respectively, while those in the high BMI group were 64.6% and 68.7%, respectively. The incidence of death in the high BMI group was lower than that of the low BMI group (P＜0.01). In multivariate analysis, BMI was an independent predictor of PFS (HR=0.282; 95% CI: 0.122-0.651; P=0.003) and an independent predictor of OS (HR=0.299; 95% CI: 0.129-0.693; P=0.005). Also, patients with B symptoms had a lower BMI than those without B symptoms (P=0.01), but BMI had no effect on patients' LDH and Ki-67. The prognosis of 16 patients treated with Auto-PBSCT was significantly better than that of the conventional chemotherapy group. There was no significant difference in BMI between Auto-PBSCT group and conventional chemotherapy group.@*CONCLUSION@#BMI is an independent prognostic factor for PFS and OS in MCL, and may be influenced by the effect of B symptoms on BMI.

The Latest Research Progress on Myelodysplastic Syndrome Patient-derived Mesenchymal Stem Cell--Review / 中国实验血液学杂志

Myelodysplastic syndrome (MDS) are a heterogeneous group of hematological malignancies. Currently, in addition to demethylated chemotherapy and hematopoietic stem cell transplantation, MDS patient-derived mesenchymal stem cells (MDS-MSC) play an important role in understanding the pathogenesis of MDS and related therapeutic targets. For example, abnormal expression of DICER1 gene, abnormalities of PI3K/AKT and Wnt/β-catenin signaling pathways provide new therapeutic targets for MDS. In addition, MDS-MSC is also affected by abnormal microenvironment of the body, such as inflammatory factor S100A9, as well as hypercoagulation and iron overload. In this review, genes, signaling pathways, cytokines, hematopoietic microenvironment, and the effect of therapeutic drugs for MDS-MSC were briefly summarized.

Association of maternal adverse childhood experiences and parenting styles with emotional behavior problems in preschool children / 中国学校卫生

Objective@#To explore the role of parenting style in the association of maternal adverse childhood experiences (ACEs) and emotional behavior problems (EBPs) in preschool children, so as to provide a reference for the prevention and control of EBPs in children.@*Methods@#A total of 6 111 children aged 3-6 years old from 36 kindergartens in 3 areas of Anhui Province in June 2021, follow up data were collected in December 2021. Maternal ACEs, mother child relationship and children EBPs were respectively assessed using the Adverse Childhood Experiences International Questionnaire(ACEs-IQ), Parental Rearing Style Scale and the difficulty score factor in the Chinese Strength and Difficulty Questionnaire(SDQ). The Bootstrap was used to examine the mediation effect of maternal parenting styles.@*Results@#Maternal ACEs were positively associated with child SDQ difficulty scores( r = 0.28, P <0.01). Negative parenting (indulgent, permissive, authoritarian and inconsistent) were positively correlated with maternal ACEs scores( r =0.28, 0.30, 0.21, 0.31) and child SDQ difficulty scores( r =0.25, 0.20, 0.20, 0.28)( P <0.01). Positive parenting (democracy) was negatively correlated with maternal ACEs and SDQ difficulty scores( r =-0.09, -0.29, P <0.01). After adjusting for confounding factors, the results of the mediation effect test of Bootstraping procedure showed that maternal parenting styles (indulgent, democracy, permissive, authoritarian and inconsistent) played a mediation role in maternal ACEs and EBPs of preschool children, and the mediation effects were respectively 19.13%, 7.34%, 24.88%, 12.05% and 26.83%.@*Conclusion@#Parenting styles play a mediating role in the association of maternal ACEs and EBPs in preschool children, and improving mothers negative parenting styles is of great significance to reduce EBPs in the offspring of maternal ACEs.

Preliminary application and efficacy analysis of transumbilical single-incision plus one port robotic total mesorectal excision / 中华胃肠外科杂志

Objective: To investigate the feasibility of transumbilical single-incision plus one port (SIPOP) robotic total mesorectal excision. Methods: Clinical data of a 70-year-old male patient with BMI 22.1 kg/m(2) who successfully underwent transumbilical single-incision plus 1 port robotic total mesorectal resection of upper rectal cancer at the General Surgery Department of Daping Hospital of Army Military Medical University on September 18, 2019 were retrospectively analyzed. Preoperative colonoscopy revealed that the distance of upper rectal cancer to anal edge was 14 cm, and the tumor size was 2.5 cm×1.5 cm×1 cm. Pathological result confirmed rectal moderately differentiated adenocarcinoma. The preoperative abdominal CT showed thickened bowel-wall of upper rectum and the blurred perirectal fat, suggesting tumor infiltration. Results: The operation was successful. There were no conversion to laparotomy or abdominal auxiliary incision, and the mesorectum of the specimen was intact. The operation time was 165 minutes, the blood loss was about 20 ml, and there were no complications such as injury to peripheral organs. Postoperative pathology showed ulcerative moderately differentiated adenocarcinoma of the upper rectum with TNM stage IVA (T4N2b). The postoperative recovery was smooth. Patient ambulated on the 1st day, the catheter was removed on the 7th day, and discharged from the hospital on the 8th day. Conclusion: The transumbilical SIPOP robotic total mesorectal excision is safe, effective and feasible.

Analysis of middle ear function of the patients with cleft palate after palatoplasty / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the middle ear function of the patients with cleft palate pre and post palatoplasty. Methods: 76 patients with cleft palate were investigated by clinical history and audiology examinations including electric otoscopy,tympanometry and click-ABR threshold. Results: The risk for middle ear function decreased with advancing age in the first 5 years. It was noticed that the otologic outcomes was related to the CP type. During long time follow-up, the frequency with the middle ear function disorder was always high within the CP patients but the proportion of the patients received tympanostomy tubes was low relatively. The prevalence of middle ear dysfunction did not differ with the time of cleft palate repair. Conclusion: The patients with cleft palate have middle ear function dysfunction in a long period of time,therefore a standard long-time follow-up system is necessary.

Efficacy analysis of Da Vinci robotic assisted and laparoscopic assisted complete mesocolic excision for right hemicolon cancer / 中华消化外科杂志

Objective:To investigate the clinical efficacy of Da Vinci robotic assisted and laparos-copic assisted complete mesocolic excision (CME) for right hemicolon cancer.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopatho-logical data of 119 patients with right hemicolon cancer who were admitted to Daping Hospital, Army Medical University from July 2016 to July 2019 were collected. There were 63 males and 56 females, aged (61±11)years. All the 119 patients underwent CME of right hemicolon. Of 119 patients, 37 cases undergoing Da Vinci robotic assisted CME of right hemicolon were divided into robotic group and 82 cases undergoing laparoscopic assisted CME of right hemicolon were divided into laparoscopic group. Observation indicators: (1) the propensity score matching conditions and comparison of general data between the two groups after propensity score matching; (2)intraoperative and postoperative situations; (3) postoperative pathological examination; (4)follow-up. Follow-up was conducted by outpatient examination or telephone interview to detect tumor metastasis and survival of patients after surgery up to August 2019. The propensity score matching was conducted by 1∶1 matching using the nearest neighbor method. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Count data were represented as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to calculate survival rate and the GraphPad Prism 5 software was used to draw survival curve. The Log-rank test was used for survival analysis. Results:(1) The propensity score matching conditions and comparison of general data between the two groups after propensity score matching: 68 of 119 patients had successful matching, including 34 cases in each group. Before propensity score matching, cases undergoing surgery by surgeon A or surgeon B were 32, 5 of the robotic group, versus 49, 33 of the laparoscopic group, showing a significant difference between the two groups ( χ2=8.381, P<0.05). After propensity score matching, the gender (males or females), age, body mass index (BMI), cases with tumor classified as stageⅠ, stage Ⅱ or stage Ⅲ of TNM staging, cases with tumor located at ileocecal region, ascending colon, hepatic flexor of colon or transverse colon, cases undergoing surgery by surgeon A or surgeon B were 17, 17, (62±10)years, (22.4±2.7)kg/m 2, 4, 14, 16, 3, 15, 10, 6, 29, 5 of the robotic group, versus 15, 19, (62±11)years, (22.4±2.8)kg/m 2, 4, 18, 12, 2, 19, 7, 6, 30, 4 of the laparoscopic group, showing no significant difference between the two groups ( χ2=0.236, t=0.127, 0.044, χ2=1.071, 1.200, 0.000, P>0.05). (2) Intraoperative and postoperative situations: after propensity score matching, the operation time, volume of intraoperative blood loss, cases undergoing conversion to open surgery, time to postoperative initial out-of-bed activities, time to postoperative first flatus, time to postoperative initial liquid food intake, duration of postoperative hospital stay and treatment expenses were (235±50)minutes, (73±45)mL, 0, (1.9±0.7)days, (2.9±1.2)days, (3.1±2.4)days, (9.1±4.9)days, (9.6±1.8)×10 4 yuan of the robotic group, versus (183±35)minutes, (74±74)mL, 1, (2.1±0.6)days, (3.3±1.4)days, (3.5±4.2)days, (9.1±3.9)days, (6.3±1.6)×10 4 yuan of the laparoscopic group, respectively. There were significant differences in the operation time and treatment expenses between the two groups ( t=5.050, 8.165, P<0.05) while there was no significant difference in the volume of intraoperative blood loss, time to postoperative initial out-of-bed activities, time to postoperative first flatus, time to postoperative initial liquid food intake or duration of postoperative hospital stay between the two groups ( t=0.118, ?0.462, ?1.129, ?1.291, 0.027, P>0.05). There was no significant difference in the conversion to open surgery between the two groups ( P>0.05). Five patients of the robotic group and 7 patients of the laparoscopic group had postoperative complications. There was no significant difference in the postoperative complications between the two groups ( χ2=0.405, P>0.05). (3) Postoperative pathological examination: after propensity score matching, cases with R 0 resection, the number of lymph node dissected, cases with lymph node metastasis and cases with tumor differentiation as well differentiated adenocarcinoma, moderately differentiated adeno-carcinoma, poorly differentiated adenocarcinoma or mucinous adenocarcinoma were 34, 17±5, 14, 1, 22, 6, 5 of the robotic group, versus 34, 17±5, 12, 2,20, 2, 10 of the laparoscopic group, respectively. There was no significant difference in the R 0 resection between the two groups ( P>0.05) and there was no significant difference in the number of lymph node dissected, lymph node metastasis and tumor differentiation between the two groups ( t=0.488, χ2=0.249, 4.095, P>0.05). (4) Follow-up: after propensity score matching, 68 patients were followed up for 1?36 months, with a median follow-up time of 24 months. The follow-up time was (20±13)months of the robotic group, versus (21±13)months of the laparoscopic group, showing no significant difference between the two groups ( t=0.409, P>0.05). During the follow-up, 3 cases of the robotic group and 4 cases of the laparoscopic group had tumor distant metastasis. The disease-free survival rate and overall survival rate at postoperative 3 years were 83.9% and 86.8% of the robotic group, versus 82.0% and 86.6% of the laparoscopic group, showing no significant difference between the two groups ( χ2=0.188, 0.193, P>0.05). Conclusion:Da Vinci robotic assisted CME for right hemicolon cancer is safe and feasible.