Short-term effect of targeted drugs on quality of life in patients with radioactive iodine-refractory differentiated thyroid cancer / 中华核医学与分子影像杂志

Objective:To analyze the short-term effect of targeted drugs on quality of life in patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC).Methods:From February 2020 to April 2022, 19 RAIR-DTC patients (10 males, 9 females; age (54.5±14.5) years) who received targeted drugs therapy (sorafenib, lenvatinib or anlotinib) in Tianjin Medical University General Hospital were prospectively enrolled. The thyroglobulin (Tg) levels prior and 1, 3, 6 months post the targeted treatment, and the adverse events were measured and recorded. Response evaluation criteria in solid tumors (RECIST) 1.1 version was used to evaluate the treatment response. The quality of life based on five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) was monitored prior and 3 months post the targeted treatment, and the prevalence rates of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression were analyzed, and the scores of health assessment were assessed. Paired t test, Kruskal-Wallis rank sum test and χ2 test were used to analyze data. Results:The prevalence rates of mobility (8/19), self-care (6/19), usual activities (10/19), pain/discomfort (10/19), and anxiety/depression (12/19) in 3 months post treatment were higher than those prior treatment (1/19, 1/19, 1/19, 2/19, 2/19; χ2 values: 4.38-11.31, all P<0.05). The score of health assessment prior treatment was (84.37±6.25), which was higher than that at 3 months post treatment (71.63±9.14; t=5.02, P=0.001). After targeted treatment, 10 patients were with skin toxicity, 8 patients were with hypertension, 8 patients were with weight loss, 7 patients were with diarrhea, 6 patients were with fatigue, 5 patients were with hepatic dysfunction, 2 patients were with proteinuria, 2 patients were with muscle pain and 1 patient was with oral ulcer. Of 19 patients, 17 insisted on continuing treatment, and the other two stopped treatment. The Tg levels at 1, 3 and 6 months post treatment were 56.26(44.60, 210.50), 53.36(41.25, 203.07) and 54.35(34.71, 223.52) mg/L, respectively, which were lower than the level prior treatment with no significant difference (110.16(49.63, 294.50) mg/L; H=2.42, P=0.490). After 3 months of targeted treatment, the progression-free survival (PFS) rate was 16/17, including 7 patients with partial response (PR), 9 patients with stable disease (SD), and 1 patient with progression of disease (PD). After 6 months of targeted treatment, the PFS rate was 10/17, including 5 patients with PR, 5 patients with SD, and 7 patients with PD. Conclusion:After 3-6 months of targeted treatment, the tumor markers of most patients are decreased with metastases improved, but the adverse events of targeted drugs have a great impact on quality of life in patients with RAIR-DTC.

Related factors for early neonatal deaths born to pregnant women with syphilis / 中华传染病杂志

Objective:To investigate early neonatal deaths born to pregnant women with syphilis and the risk factors.Methods:Data were obtained from the maternal syphilis surveillance system in Zhejiang Province. Pregnant women with syphilis who delivered ≥28 weeks during January 2014 to December 2020 were included. Demographic characteristics (age, education level, occupation, gravidity, parity, adverse pregnancy history, etc.), maternal and perinatal health records, syphilis laboratory test results, syphilis treatment regimen, delivery information, and infant information were collected. Trend chi-square analysis was conducted to track the early neonatal mortality over years. Pearson correlation coefficient was used to estimate the relationship between maternal syphilis treatment and early neonatal mortality. Logistic analysis was conducted to investigate the risk factors for early neonatal death.Results:Among the 71 cases with early neonatal death, 49 cases (69.01%) were aged from 21 to 34 years old, 52 cases (73.24%) had middle school education, 39 cases (54.93%) had no fixed occupation, 39 cases (54.93%) had more than three gravidities, 48 cases (67.61%) were multiparas. There were eight cases (11.27%) of stillbirth abortion. Forty-nine cases (69.01%) with rapid plasma reagin circle card test (RPR) or tolulized red unheated serum test (TRUST) titer ≥1∶4. Among the 72 early neonatal deaths, 40 were males and 32 were females. The leading cause of death was preterm birth/low birth weight (56 cases, 77.78%). From 2014 to 2020, the early neonatal mortality rate of pregnant women with syphilis in Zhejiang Province decreased from 10.37‰ (24/2 314) to 1.49‰(3/2 007) (trend χ2=20.05, P<0.001). The rate of maternal antisyphilitic treatment was negatively correlated with early neonatal mortality ( r=-0.895, P=0.006). Multivariate analysis showed that standard treatment reduced the risk of early neonatal death (Wald=24.845, P<0.001, odds ratio ( OR)=0.181). However, RPR or TRUST titer ≥1∶4 in the last trimester (Wald=72.026, P<0.001, OR=10.112) increased the risk of early neonatal death. Conclusions:Preterm birth and low birth weight are the leading causes of early neonatal death in pregnant women with syphilis. Strengthening the treatment of syphilis in pregnancy women, especially the standard treatment, is beneficial to reduce the risk of early neonatal death.

Comparison of efficacy and safety of microwave ablation and radiofrequency ablation for benign thyroid nodules / 中国医师杂志

Objective:To compare the efficacy and safety of ultrasound-guided microwave ablation(MWA) and radiofrequency ablation (RFA) in the treatment of benign thyroid nodules.Methods:The clinical data of 119 patients (187 nodules in total) with benign thyroid nodules who were treated with ultrasond-guided MWA (56 cases) and RFA (63 cases) in Shenzhen Third People′s Hospital from January 2018 to January 2020 were retrospectively analyzed. The ablation time, ablation time per unit volume, volume reduction rate of thyroid nodules after treatment, changes in thyroid function before and after treatment, and incidence of complications were compared between the two groups.Results:The ablation time and ablation time per unit volume in the MWA group were significantly shorter than those in the RFA group (all P<0.05). At 3, 6, and 12 months after treatment, the reduction rate of nodule volume in MWA group was higher than that in RFA group, and the difference was statistically significant in the subgroup with nodule >10 ml (all P<0.05). The incidence of temporary hoarseness in RFA group [6.35%(4/63)]was lower than that in MWA group [12.5%(7/56)], with no statistically significant difference ( P>0.05). Conclusions:Microwave ablation is more effective than radiofrequency ablation in the treatment of large thyroid nodules. Radiofrequency ablation is safer than microwave ablation for thyroid nodules near the risk triangle, but further research is needed to confirm.

Research progress on metabolites of intestinal flora and food addiction in diabetic patients / 中华临床营养杂志

Appetite is a physiological and psychological factor that governs food intake and food selection. It is regulated by central nerve nuclei, transmitters, peripheral receptors and appetite related factors. Food addiction(FA) and diabetes are related physiologically and pathologically, and are reciprocal independent risk factors. According to research, food addiction is categorized within the subgroup of metabolic diseases such as obesity and diabetes and is regulated by the mesolimbic dopamine system in the brain, driving extreme hedonic overeating behavior. Food addiction is closely associated with genetic and environmental factors. Many products of intestinal flora metabolism are also involved in the occurrence and development of food addiction. In turn, food addiction also causes changes in intestinal flora metabolites. This article focuses on the correlation between intestinal microbial metabolites and food addiction in diabetic patients.

To explore the characteristics of nerve injury in patients with diabetic peripheral neuropathy and the predictive value of current perception threshold combined with nerve conduction velocity / 中国医师进修杂志

Objective:To analyze the characteristics of nerve injury in patients with diabetic peripheral neuropathy (DPN) and explore the diagnostic value of current perception threshold (CPT) and nerve conduction velocity (NCV) for DPN.Methods:One hundred and thirty-six DPN patients admitted to Beijing Puren Hospital from June 2017 to December 2019 were selected, and 130 diabetic non-DPN patients admitted during the same period were used as controls. All the subjects were tested by CPT and NCV. Among them, the detection of NCV included sensory nerve conduction velocity (SCV) and motor nerve conduction velocity (MCV). Statistical analysis was performed on the relevant indicators of the two groups of subjects.Results:The CPT values of the upper limb median nerve and ulnar nerve at 2 000 Hz, 250 Hz, and 5 Hz, the superficial peroneal nerves at 250 Hz, and 5 Hz, and the CPT values of the sural nerve at 2 000 Hz and 250 Hz were higher than those of non-DPN patients, DPN injury mainly occurred in myelinated nerve fibers in the lower extremities [60.29%(82/136)], and the difference were statistically significant ( P<0.05). The SCV and MCV of the median nerve, ulnar nerve, and common peroneal nerve in the DPN group were lower than those in the non-DPN group, the SCV abnormal rate was higher than the MCV: 55.88%(76/136) vs. 37.50%(51/136); 58.82%(80/136) vs. 41.18% (56/136); 67.65%(92/136) vs. 50.00%(68/136), and the differences were statistically significant ( P<0.05). The area under the predictive value curve (AUC) of CPT for DPN was 0.815 (95% CI 0.735 ~ 0.895). The AUC of NCV for DPN was 0.875 (95% CI 0.813 ~ 0.944). The AUC of CPT and NCV for DPN was 0.923 (95% CI 0.876 ~ 0.970). Conclusions:DPT patients have abnormal CPT and NCV, and nerve damage occurs mostly in myelinated nerve fibers and SCV. Diagnosing DPN by combining CPT and NCV is helpful to improve the detection rate of DPN.

Identification and preservation of arm lymphatics in axillary lymph node dissection to prevent arm lymphedema: a single center randomized controlled trial / 中华肿瘤杂志

Objective: To evaluate the feasibility of identification and preservation of arm lymphatics (DEPART) in axillary lymph node dissection (ALND) for breast cancer to prevent arm lymphedema. Methods: A randomized controlled study method was used. Two hundred and sixty-five patients who underwent breast cancer surgery at the Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University from November 2017 to June 2018 were included, and the patients were randomly divided into ALND+ DEPART group (132 patients) and standard ALND group (133 patients) by random number table method. In the ALND+ DEPART group, indocyanine green and methylene blue were injected as tracers before surgery, and the arm sentinel nodes was visualized by staged tracing during intraoperative dissection of axillary lymph nodes. Partial frozen sections were made of arm lymph nodes >1 cm in length and hard and suspicious of metastasis, and arm lymph nodes and lymphatic vessels were selectively preserved. Patients in the standard ALND group underwent standard ALND. Objective and subjective indexes of arm lymphedema were evaluated by 5-point circumference measurement and Norman questionnaire. Results: Among 132 breast cancer patients in the ALND+ DEPART group, 121 (91.7%) completed DEPART. There were no statistically significant differences in age, body mass index, pathological type, dissection number of axillary lymph node, N stage, TNM stage, molecular typing, and regional radiotherapy between the ALND+ DEPART and standard ALND groups (P>0.05). At a median follow-up of 24 months, assessment by the 5-point circumference measurement showed that the incidence rates of lymphedema in the ALND+ DEPART and standard ALND groups were 5.0% (6/121) and 15.8% (21/133), respectively, with statistically significant differences (P=0.005). Assessment by the Norman questionnaire showed that the incidence rates of lymphedema in the ALND+ DEPART and standard ALND groups were 5.8% (7/121) and 21.8% (29/133), respectively, with a statistically significant difference (P<0.001). No local regional recurrence was observed in either group during the follow-up period. Conclusion: For breast cancer patients with positive axillary lymph nodes, the administration of DEPART during ALND can reduce or avoid the occurrence of arm lymphedema without compromising oncology safety.

Observational study of macular capillary perfusion with branch retinal vein occlusion by using DART-OCTA / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the imaging characteristics of dense automatic real time B-scan optical coherence tomography angiography(DART-OCTA)in macular-involved branch retinal vein occlusion(BRVO)and the diagnostic value of capillary perfusion imaging in the macular area.METHODS: From June 2020 to December 2020, there were 51 cases of 51 eyes with BRVO diagnosed in Eye Hospital, Wenzhou Medical University. Imaging characteristics of the BRVO macular area were observed by fluorescein angiography(FA), optical coherence tomography angiography(OCTA)and DART-OCTA examination, respectively. According to the retinal capillary perfusion status, the included patients were divided into capillary and non-imaging groups, comparing the results of capillary perfusion imaging in the BRVO macular area among the three examination methods.Furthermore, quantitative analysis of capillary perfusion density in the lesion involved area and the lesion non-involved area was performed in DART-OCTA images. RESULTS: Patients with 51 eyes were included in this study, FA identified 10 eyes of capillary perfusion imaging, OCTA identified 14 eyes of capillary perfusion imaging, DART-OCTA identified 34 eyes of the capillary perfusion imaging.Comparison of the three test methods for capillary perfusion imaging findings in the BRVO macular area showed that DART-OCTA was more sensitive compared to FA and OCTA for capillary perfusion imaging in the ischemic area. In DART-OCTA examination, retinal capillary blood flow density was lower in the lesion-involved areas in both the capillary perfusion imaging group and the non-imaging groups(0.65±0.20/mm vs 1.16±0.31/mm,0.41±0.16/mm vs 1.06±0.38/mm, all P<0.0001).CONCLUSION: DART-OCTA can provide clearer tomographic imaging of retinal capillary perfusion. And the imaging with its observation of BRVO involving the macular area is least affected by macular hemorrhage and it is an important complementary method for BRVO patients with significant retinal hemorrhage.

Comparison of perioperative result and complications of robot-assisted radical cystectomy with intracorporeal and extracorporeal urinary diversion / 中华泌尿外科杂志

Objective:To explore and compare the perioperative result and complications of robot-assisted radical cystectomy with intracorporeal and extracorporeal urinary diversion.Methods:Clinical data of bladder cancer patients undergoing robot-assisted radical cystectomy with ileal conduit in Zhejiang Provincial People's Hospital from January 2015 to March 2020 were retrospectively analyzed. Eighty-two patients underwent extracorporeal urinary diversion (ECUD group), and 122 underwent intracorporeal urinary diversion (ICUD group). In the ECUD group, the median age was 70(61, 76)years old, including 67 male (81.7%), the median BMI was 26.1(24.3, 28.5), 67 cases(81.7%) was ASA score 0-2, 15 cases (18.3%)was 3 or higher, 15 cases (18.3%) were high risk non-muscular invasive bladder cancer. 67 cases (81.7%) were muscular invasive bladder cancer. 16 cases (19.5%) received neoadjuvant chemotherapy. Past medical history included smoking in 35 cases (43.2%), hypertension in 31 cases (37.5%), diabetes in 17 cases (21.3%), heart disease in 13 cases (15.7%), and abdominal surgery in 15 cases (17.8%). In the ICUD group, the median age was 68 (62, 75), 95 male (77.9%), the median BMI was 25.6 (23.4, 27.8)kg/m 2, 105 cases(86.1%) was ASA score 0-2, 17 cases (13.9%)was 3 or higher, 29 cases (24.9%) were high risk non-muscular invasive bladder cancer, and 93 cases (75.1%) were muscular invasive bladder cancer. There were 22 cases (18.0%) undergoing neoadjuvant chemotherapy. Past medical history included smoking in 58 cases (47.3%), hypertension in 44 cases (32.6%), diabetes in 33 cases (22.8%), heart disease in 28 cases (26.7%), and abdominal surgery in 17 cases (14.2%). No significance was detected in characteristics between the two groups. For ileal bladder making and ureteral implantation method in ICUD group, 15 cm ileum was taken using stapler at the 15 cm from ileocecum to make ileal conduit and restore the continuity of the ileum. The proximal end of the ileal conduit was closed. The bilateral ureteral were implanted 3 cm apart on the ileal bladder. F6 single J tube was placed into both of the ureters to drain urine. For ECUD group, the subumbilical 5 cm incision was taken to enter the abdominal cavity. The ileocecum was found and the terminal ileum was taken out of the body. A segment of 15 cm in length ileocecum 15 cm away from the cecum was cut off with a linear cutting stapler and the blood vessels of arterial arch were ligated, then a small opening at the same ileum position was cut. The continuity of the ileocecum was restored. The ileal conduit was irrigated, and the bilateral ureters were placed into a single J tube and anastomosed to the ileal conduit 3 cm apart. The operation time, intraoperative blood loss, postoperative exhaust time, postoperative feeding time, postoperative hospital stay, postoperative incision pain score, postoperative readmission rate, peri-operative mortality, postoperative complications and pathology results were compared between the two groups. Results:All cases were successfully performed robotically without conversion or major intraoperative complications. There was no significant difference in operation time between ICUD group and ECUD group [260(230, 310) min and 235(220, 290) min, P=0.078]. The estimated blood loss in ECUD group was more than that in ICUD group [300(200, 400) ml and 150(100, 300), P=0.037], but there was no difference in blood transfusion rate between the two groups [7(8.6%) and 9(7.4%), P=0.196]. The exhaust time [4(2-6) days and 2(1, 3) days] and postoperative solid food feeding time [7(4, 9) days and 4(3, 5) days] in the ECUD group were longer than those in the ICUD group (all P<0 05). The exhaust time[4(2-6)day and 2(1, 3)day] and solid food feeding time[7(4, 9)day and 4(3, 5)day] in ECUD group were longer than those in ICUD group. There was no significant difference in postoperative hospital stay between ECUD group and ICUD group[8(5, 11)day and 6(5, 9)day, P=0.212]. Clavien-Dindo Ⅰ-Ⅱ grade was defined mild complication, Ⅲ grade or above was defined serious complication, early complication was defined within 30 days after operation, and late complication was defined 30-90 days after operation. The overall early postoperative complication rate were 19.6%(24) and 34.2%(28)(ICUD vs.ECUD), the mild complications rate were 13.9%(17) and 25.6%(21)(ICUD vs.ECUD), and the late severe complication rate were 4.1%(5)and 10.1%(8)(ICUD vs.ECUD). ICUD group were significantly lower than those of ECUD group (all P<0.05). There was no difference in the early severe complication rate [5.7%(7) and 8.5%(7)], the total late complication rate [15.6%(19) and 16.1%(13)], and the late mild complication rate [11.5% (14) and 6.0% (5)] (all P>0.05). There was no significant difference between ICUD group and ECUD group, in term of the number of lymph nodes dissected [21(14, 25) and 19(15, 24)], the positive rate of lymph nodes [10.7%(13) and 10.0%(8)], the positive rate of surgical margin [3.3%(4) and 4.8%(4)] and postoperative pathological stage T 1-T is [25(20.3%) and 14(17.1%)], and T 2-T 3 [97(79.7%) and 68(82.9%)]. The number of patients with postoperative incision pain (pain score >5) was 43 (35.6%) in ICUD and 46 (56.5%) in ECUD( P< 0.05). The 30-day and 90-day readmission rates were 1.6% (2/82) and 4.9% (6/82) in ICUD group, and 1.2% (1/122) and 9.8% (8/122) in ECUD group, respectively. There was no peri-operative mortality in both groups. Conclusions:Robot-assisted radical cystectomy with ileal conduit is a safe and repeatable method for the treatment of muscular invasive or high-risk non-muscular invasive bladder cancer. Complete intracorporeal bladder reconstruction is feasible and has the advantages of less intraoperative bleeding, faster postoperative intestinal function recovery and less complications.

Targeting TSHR and ICAM-1 for treatment of Graves′ disease in BALB/c mice / 中华核医学与分子影像杂志

Objective:To explore new methods of treating Graves′ disease (GD) by targeting thyroid stimulating hormone receptor (TSHR) and intercellular adhesion molecule-1 (ICAM-1).Methods:The small interfering RNA (siRNA) targeting TSHR and the ICAM-1 monoclonal antibody (mAb) were designed and synthesized. Thirty GD model mice were randomly divided into siRNA treatment group, ICAM-1 mAb treatment group, and untreated GD group (10 mice in each group), and 10 normal mice were taken as blank control. Serum thyroxine (T 4), thyroid stimulating hormone (TSH), TSH receptor-stimulating antibody (TSAb) and TSH-stimulation blocking antibody (TSBAb) were measured before and after treatment. At the end of the treatment, body mass and heart rate of mice in each group were measured, and thyroid uptake of 99Tc mO 4-, thyroid size and pathological changes were evaluated. Independent-sample t test, paired t test and one-way analysis of variance were used to analyze data. Results:After three treatments, the body mass of mice in siRNA group and ICAM-1 mAb group were significantly lower than that of normal mice ( F=3.50, P=0.025); the heart rates of the mice in two groups were significantly lower than that of untreated GD mice ( F=24.73, P<0.001). Heart rate of mice treated with siRNA decreased significantly, close to that of normal mice. After treatment, the serum T 4((27.58±1.94) vs (65.71±6.89) μg/L, (27.24±3.50) vs (70.84±8.46) μg/L), TSAb ((331.44±43.38) vs (457.33±45.85) mU/L, (275.16±45.80) vs (443.91±42.32) mU/L) and TSBAb ((13.94±1.11) vs (15.83±5.92) mU/L, (14.59±1.02) vs (17.05±6.16) mU/L) levels of mice in both siRNA group and ICAM-1 mAb group significantly decreased ( t values: 4.45-10.87, all P<0.05), while the serum TSH levels of mice in two groups significantly increased ((0.13±0.05) vs (0.04±0.05) mU/L, (1.46±0.34) vs (0.06±0.03) mU/L; t values: -2.22, -5.87, P values: 0.007, <0.001). The elevated TSH level and decreased TSAb level of mice treated with ICAM-1 mAb were significantly different from those treated with siRNA ( t values: 1.03, -1.63, P values: 0.002, 0.031). After treatment, the uptake of 99Tc mO 4- in part of the thyroid lobes of mice was decreased, and the enlargement degree of the corresponding lobes was reduced. The thyroid pathology of mice in the treated groups showed that the absorption vacuoles of thyroid follicles were reduced, and the phenomenon of thinner colloids was improved. No obvious damage was observed in the heart, liver and kidneys of the mice. Conclusions:Both the siRNA targeting TSHR and ICAM-1 mAb have therapeutic effects on GD model mice. The siRNA is better at controlling heart rate, and ICAM-1 mAb is better at increasing TSH and decreasing TSAb. Each of the above treatment methods is safe and effective, which can provide new ideas for GD targeted therapy.

Effect of spinal manipulation therapy on chronic nonspecific neck pain: a meta-analysis / 中国康复理论与实践

@#Objective To evaluate the effects of spinal manipulation therapy (SMT) on chronic nonspecific neck pain (CNSNP) by using World Health Organization Family International Classifications (WHO-FICs). Methods Randomized controlled trials (RCTs) about the effects of SMT on CNSNP were searched from PubMed, Web of Science, Cochrane Library, EMBASE, EBSCO, CBM and CNKI from database establishment to December 31st, 2021. At least two researchers extracted the data. Cochrane bias risk assessment tool and Physiotherapy Evidence Database Scale were used to evaluate the quality of the included articles. Revman 5.4 software and Stata 16.0 software were used for meta-analyses and publication bias analysis respectively. Results A total of 15 RCTs that represented 1 067 participants were evaluated. In terms of body functions, compared with the control group, SMT significantly reduced Visual Analog Score for pain (MD = -0.85, 95%CI -1.06 to -0.63, P < 0.00001) and Numerical Rating Scale (MD = -0.92, 95%CI -1.29 to -0.55, P < 0.001), increased pressure pain thresholds (SMD = 0.67, 95%CI 0.47 to 0.86, P < 0.001), cervical range of motion (ROM) of flexion/extension (SMD = 0.51, 95%CI 0.33 to 0.68, P < 0.001) and rotation (SMD = 0.20, 95%CI 0.01 to 0.38, P = 0.04), improved root mean square of cervical muscles electromygraphy (MD = 2.17, 95%CI 0.06 to 4.29, P = 0.04), but not significantly in cervical ROM of lateral flexion (SMD = 0.19, 95%CI -0.00 to 0.38, P = 0.06), cervical strength (SMD = -0.18, 95%CI -0.84 to 0.49, P = 0.60) and endurance (SMD = 0.18, 95%CI -0.39 to 0.75, P = 0.53). In term of activities and participation, SMT significantly improved cervical disability (MD = -0.96, 95%CI -1.55 to -0.38, P = 0.001), but not significantly in health status of patients with CNSNP (SMD = 0.08, 95%CI -0.03 to 0.20, P = 0.15). Conclusion SMT could improve pain intensity, pain sensitivity, cervical ROM and disability in patients with CNSNP, but its efficacy on muscle function, proprioception and health status is unclear.

Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice / 国际口腔科学杂志·英文版

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4 (Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2 and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore, Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.

Effectiveness of interventions for human papillomavirus vaccine hesitancy among female university students based on the precaution adoption process model / 预防医学

Objective @#To evaluate the effectiveness of interventions for human papillomavirus ( HPV ) vaccine hesitancy among female university students based on the precaution adoption process model (PAPM), so as to provide the evidence for improving the coverage of HPV vaccine in this population. @*Methods @#HPV vaccine hesitant female students were selected using a cluster sampling method from Zhejiang Chinese Medical University, and randomly assigned to the PAPM group and control group. Students in the PAPM group received PAPM-based interventions for HPV vaccine hesitancy, while students in the control group were given routine interventions. The HPV-related knowledge, HPV vaccine-related knowledge and HPV vaccine hesitancy scores were collected from both groups prior to interventions ( T0 ), 0 ( T1 ), 1 ( T2 ) and 3 months post-interventions ( T3 ), and the effectiveness of interventions was evaluated using analysis of variance for repeated measures.@*Results @#There were 147 students in the PAPM group and 141 students in the control group. In the PAPM group, 36.73% of the students majored in medical sciences, and 48.23% were freshmen; in the control group, 39.72% majored in medical sciences, and 50.35% were freshmen. The mean scores of HPV- and HPV vaccine-related knowledge were significantly greater in the PAPM group than in the control group, respectively ( T1, 5.29 vs. 4.91; T2, 4.27 vs. 4.22; T3, 4.22 vs. 4.04; P<0.05 ); however, no significant differences were detected in the HPV vaccine hesitancy scores between the two groups, respectively ( T1, 2.98 vs. 2.95; T2, 3.07 vs. 3.07; T3, 3.08 vs. 2.97; P>0.05 ). The mean scores of the confidence dimension ( T1, 3.37 vs. 3.23; T2, 3.48 vs. 3.40; T3, 3.38 vs. 3.25 ) and the dimension of influence by others ( T1, 3.44 vs. 3.33; T2, 3.42 vs. 3.37; T3, 3.46 vs. 3.27 ) were significantly greater in the PAPM group than in the control group (P<0.05), while the mean scores of the complacency dimension were significantly lower in the PAPM group than in the control group ( T1, 1.98 vs. 2.03; T2, 2.06 vs. 2.20; T3, 2.18 vs. 2.15; P<0.05 ).@*Conclusions @#PAPM-based interventions for HPV vaccine hesitancy may effectively improve the awareness of HPV and HPV vaccines, reduce complacency, and enhance the influence by others among female university students.

Effects of different routes of heparin on instant blood-mediated inflammatory reaction after portal vein islet transplantation / 中南大学学报(医学版)

OBJECTIVES@#Heparin is mainly used as an anticoagulant in clinic, and it also has a certain anti-inflammatory effect. At present, after portal vein islet transplantation in diabetic patients, heparin is mainly infused through the peripheral veins of the limbs to achieve the purpose of anticoagulation and protection of the graft, rather than through the portal vein. In this study, animal experiments were conducted to investigate the effect of heparin infusion via the portal vein and marginal ear vein on the instant blood-mediated inflammatory reaction (IBMIR) after portal vein islet transplantation, which is the choice of anticoagulation methods for clinical islet transplantation to provide a basis for decision-making.@*METHODS@#A total of 50 neonatal pigs (Xeno-1 type, 3-5 days) were selected. Islets were isolated and purified from the pancreas of neonatal pigs. Ten non-diabetic Landrace pigs (1.5-2.0 months) served as recipients, and 12 000 IEQ/kg neonatal porcine islets were transplanted into the liver through the portal vein. All recipients received bolus injection of 50 U/kg of heparin 10 minutes before transplantation. After the bolus injection of heparin, the experimental group received heparin via the portal vein [10 U/(kg·h), 5 recipients], and the control group received heparin via the marginal ear vein [10 U/(kg·h), 5 recipients]. The superior vena cava blood was collected from the 2 groups pre-operation at 1, 3, 24 h post-operation of the transplantation. The portal vein blood was collected from the experimental group at 1 and 3 h after the transplantation as well. The levels of complement C3a, C5a, thrombin-antithrombin complex (TAT), β-thromboglobulin (β-TG), and D-dimer as well as activated partial thromboplastin time (APTT) in superior vena cava blood from 1 and 3 h post-transplantation were detected in the 2 groups, and the levels of anti-Xa and anti-IIa in the portal vein and superior vena cava blood from 1 and 3 h post-transplantation in the experimental group were detected. Twenty four hours after the transplantation, the liver tissues in the 2 groups were collected for pathological examination to observe the inflammatory cell infiltration and peripheral thrombosis around the islets graft in liver.@*RESULTS@#Before transplantation, there was no statistically significant difference in C3a, C5a, TAT, β-TG, D-dimer levels and APTT between the 2 groups (all P>0.05). At 1 and 3 h after transplantation, the C3a, TAT, and D-dimer levels in the experimental group were significant decreased than those in the control groups (all P<0.05), and at 3 h after transplantation the C5a was significant decreased than that in the control group (P<0.05). At 1 and 3 h after transplantation, the anti-Xa and anti-IIa levels in the portal vein blood were significantly increased than those in the superior vena cava blood in the experimental group (all P<0.05). Pathological results showed the presence of islet cell clusters in the liver blood vessels. The thrombus formation and neutrophil infiltration around islet graft was not obvious in the experimental group, while massive thrombus formation and neutrophil infiltration in the control group.@*CONCLUSIONS@#Compared with marginal ear vein infusion of heparin, the direct infusion of heparin in the portal vein has a certain inhibitory effect on complement system, coagulation system activation and inflammatory cell infiltration in portal vein islet transplantation, which may attenuate the occurrence of IBMIR.

Effect of computer virtual technique combined with pelvic reduction frame in the treatment of type C pelvic fracture / 中国骨伤

OBJECTIVE@#To investigate the short-term clinical effect of the computer virtual technique combined with pelvic reduction frame in the treatment of complex pelvic fractures.@*METHODS@#Thirty patients with Tile C pelvic fractures treated by percutaneous minimally invasive pelvic reduction frame from April 2018 to April 2020 were retrospectively analyzed, including 21 males and 9 females, aged from 19 to 57 (39.40±9.85) years old. The patient's pelvic CT DICOM data were imported into Mimics software to reconstruct the virtual fracture model. Virtual reduction and nail placement were carried out on the fracture model, and then simulated fluoroscopy was carried out to record the ideal fluoroscopy orientation and angle to guide the correct fluoroscopy during operation. The operation time, fluoroscopy times and intraoperative blood loss were recorded. The quality of fracture reduction was evaluated by Matta image score standard, and the postoperative function was evaluated by Majeed function score standard.@*RESULTS@#All 30 patients achieved closed reduction and percutaneous screw fixation. According to Matta score, the excellent and good rate of fracture reduction was 93.3%(28/30). A total of 67 channel screws were inserted, and the excellent and good rate was 98.5%(66/67). The operation time was (173.54±79.31) min, fluoroscopy time was (90.81±41.11) times, intraoperative blood loss was (81.21±43.97) ml. All incisions healed at one stage without broken nails or re-displacement of fractures. All patients were followed up for 12 months. At the final follow-up, Majeed function score was 73 to 94(85.66±5.33) scores.@*CONCLUSION@#Computer virtual technology combined with pelvic reduction frame could rapidly, accurately and safely reduce and fix unstable pelvic fractures. Computer virtualization could help surgeons to recognition and understanding pelvic fractures, pelvic reduction frame could improve the surgeon's ability to manage complex and unstable pelvic injuries.

Network Meta-analysis of oral blood-activating and stasis-removing Chinese patent medicines in treatment of hypertensive left ventricular hypertrophy / 中国中药杂志

This study was designed to assess the clinical efficacy of oral blood-activating and stasis-removing Chinese patent medicines in treating hypertensive left ventricular hypertrophy(LVH) based on network Meta-analysis. The clinical randomized controlled trials(RCTs) concerning the treatment of hypertensive LVH with oral blood-activating and stasis-removing Chinese patent medicines were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, and Cochrane Library from their inception to September 2021. Two researchers independently completed the literature screening, data extraction, and quality evaluation. The data were then analyzed by RevMan 5.3, Stata 15.1, and ADDIS 1.16.8. Finally, a total of 31 RCTs were included, involving 3 001 patients and four oral blood-activating and stasis-removing Chinese patent medicines. In terms of the alleviation of heart damage, the Chinese patent medicines combined with conventional western medicine groups were superior to the conventional western medicine groups in lo-wering the left ventricular mass index(LVMI). There was no significant difference in LVMI, left ventricular ejection fraction(LVEF), or the ratio of early diastolic peak flow velocity to late diastolic peak flow velocity(E/A) between different Chinese patent medicines combined with conventional western medicine groups. Xinnao Shutong Capsules/Tablets combined with conventional western medicine had the best efficacy in reducing LVMI and elevating LVEF, while Xinkeshu Capsules/Tablets combined with conventional western medicine had the best effect in improving E/A. In the control of blood pressure, when all Chinese patent medicines except for Xinnao Shutong Capsules/Tablets were combined with conventional western medicine, the resulting systolic blood pressure(SBP) and diastolic blood pressure(DBP) were significantly lower than those in the conventional western medicine group. Xinkeshu Capsules/Tablets combined with conventional western medicine produced the best effect in reducing SBP and DBP, followed by Xinnao Shutong Capsules/Tablets. In terms of safety, no serious adverse reactions occurred in all trials. The four oral blood-activating and stasis-removing Chinese patent medicines included in this study exhibited obvious advantages in the treatment of hypertensive LVH when they were combined with conventional western medicine, with the best effects observed in the Xinnao Shutong Capsules/Tablets combined with conventional western medicine group. However, due to the limitation of the quantity and quality of the included articles, the conclusion of this study still needs to be verified by more high-quality, multi-center, and large-sample RCTs.

MiR-322-5p Alleviates Cell Injury and Impairment of Cognitive Function in Vascular Dementia by Targeting TSPAN5

Purpose@#As the population ages, the incidence of clinical dementia has been rising around the world. It has been reported that microRNAs act as key diagnostic biomarkers and targets for various neurological conditions, including dementia. MiR-322-5p has been revealed to play an important role in multiple diseases. In this study, we aimed to investigate the role and regulatory mechanism of miR-322-5p in vascular dementia. @*Materials and Methods@#In this study, neonatal rat neurons (NRNs) were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to induce cell injury. The animals were subjected to permanent bilateral occlusion of the carotid arteries (2-vessel occlusion, 2VO) to induce the model of chronic brain hypoperfusion. @*Results@#MiR-322-5p expression was significantly downregulated in the neurons exposed to OGD/R and the hippocampi of 2VO rats. Overexpression of miR-322-5p ameliorated cell apoptosis and the inflammatory response in vitro. In a mechanistic study, miR-322-5p was confirmed to directly target and negatively regulate tetraspanin 5 (TSPAN5) in cultured NRNs. Moreover, overexpression of TSPAN5 could counteract the effects of miR-322-5p overexpression on cell apoptosis and the inflammatory response in OGD/Rtreated neurons. More importantly, miR-322-5p improved cognitive ability and inhibited inflammatory production in 2VO rats. @*Conclusion@#Overall, the results suggest that miR-322-5p alleviates vascular dementia development by targeting TSPAN5. This discovery may provide a potential therapeutic target for dementia.

Longitudinal study on the trajectory and influencing factors of cancer-related fatigue in breast cancer patients during chemotherapy / 中国实用护理杂志

Objective:To investigate the longitudinal trajectory and influencing factors of cancer-related fatigue (CRF) in breast cancer patients during chemotherapy.Methods:From March 2019 to January 2020, breast cancer patients in Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine and Peking Union Medical College Hospital were selected as the research objects to conduct follow-up investigation. The survey tools included general information questionnaire, Cancer-related Fatigue Assessment Scale, International Physical Activity Questionnaire, and the Pittsburgh Sleep Quality Index Scale.Results:A total of 91 patients were included in the study. The incidence of severe CRF at each time point before chemotherapy, 3 weeks after chemotherapy and 6 weeks after chemotherapy were 1.1% (1/91), 8.8% (5/57) and 2.1% (1/48), respectively. The results of the generalized estimation equation showed that the trajectory of the total score CRF firstly increased and then decreased, reaching a peak at 3 weeks after chemotherapy (35.45±13.07), and mild CRF change showed statistical difference ( P<0.05). In addition, BMI and sleep and daytime dysfunction were the influencing factors of the total score of CRF. Disease stage, sleep disturbance and daytime dysfunction were the influencing factors of CRF with different severity. Conclusions:CRF is a prominent problem in breast cancer patients during chemotherapy. Attention should be paid to high-risk individuals with abnormal BMI and daytime function by medical staff.

Nucleomodulin BspJ as an effector promotes the colonization of Brucella abortus in the host

Background@#Brucella infection induces brucellosis, a zoonotic disease. The intracellular circulation process and virulence of Brucella mainly depend on its type IV secretion system (T4SS) expressing secretory effectors. Secreted protein BspJ is a nucleomodulin of Brucella that invades the host cell nucleus. BspJ mediates host energy synthesis and apoptosis through interaction with proteins. However, the mechanism of BspJ as it affects the intracellular survival of Brucella remains to be clarified. @*Objectives@#To verify the functions of nucleomodulin BspJ in Brucella's intracellular infection cycles. @*Methods@#Constructed Brucella abortus BspJ gene deletion strain (B. abortus ΔBspJ) and complement strain (B. abortus pBspJ) and studied their roles in the proliferation of Brucella both in vivo and in vitro. @*Results@#BspJ gene deletion reduced the survival and intracellular proliferation of Brucellaat the replicating Brucella-containing vacuoles (rBCV) stage. Compared with the parent strain, the colonization ability of the bacteria in mice was significantly reduced, causing less inflammatory infiltration and pathological damage. We also found that the knockout of BspJ altered the secretion of cytokines (interleukin [IL]-6, IL-1β, IL-10, tumor necrosis factor-α, interferon-γ) in host cells and in mice to affect the intracellular survival of Brucella. @*Conclusions@#BspJ is extremely important for the circulatory proliferation of Brucella in the host, and it may be involved in a previously unknown mechanism of Brucella's intracellular survival.

The influence of age and thyroglobulin antibody positive level on the prognosis of differentiated thyroid cancer / 中华内分泌代谢杂志

Objective:To investigate the prognostic factors of differentiated thyroid cancer (DTC) patients with positive thyroglobulin antibody (TgAb) and varying ages after operation and 131I treatment. To explore the value of TgAb level and its change in the prognosis of DTC patients. Methods:Clinical data of 131 TgAb positive DTC patients were retrospectively analyzed. According to age, they were divided into young group(age<55 years, n=95) and elder group (age≥55 years, n=36). According to response, it was divided into excellent response group (110 cases) and non-excellent response group (21 cases). χ2 test and t test were used to compare the clinicopathological features between excellent response group and non-excellent response group. By logistic regression analysis, the independent risk factors affecting the prognosis of patients were analyzed. The receiver operating characteristic curve was used to determine the TgAb value of persistent or recurrent DTC, and the Kaplan-Meier regression curve was used to analyze the time of TgAb becoming negative. P<0.05 was statistically significant. Results:In young patients, the higher serum TgAb level before 131I treatment and the lateral lymph node metastasis were the independent influencing factors of poor prognosis [ OR=0.89(95% CI 0.83-0.95), OR=0.15(95% CI 0.05-0.52); both P<0.05]. In elder group, extraglandular invasion and higher serum TgAb before 131I treatment were associated with poorer prognosis [ OR=0.05(95% CI 0-0.83), OR=0.91(95% CI 0.76-1.13); P<0.05]. The serum TgAb thresholds for predicting DTC persistence/recurrence were 315.5 IU/mL(246.0 IU/mL in the young group and 516.5 IU/mL in the elder group). The mean time TgAb sera turned negative was (26.37±2.22) months [(23.28±2.37) months for young group and (32.64±4.07) months for elder group]. The TgAb decreased >50% in one year of the patients who had a lower probability of disease persistence/recurrence than the group without ( P<0.05). Conclusions:The high level of serum TgAb before 131I treatment and lateral lymph node metastasis were independent factors of poor prognosis in young patients, while in elder patients, extraglandular tumor invasion and the high level of serum TgAb before 131I treatment were independent factors of poor prognosis. The rate of TgAb change one year after treatment may be used as an early marker for predicting the disease status of TgAb positive patients.