OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

There was a 61-year-old male patient with cutaneous metastatic lung adenocarcinoma inoculated along a thoracic drainage tube treated in Zhongshan Hospital,Fudan University.The duration of disease was over 2 weeks.The skin lesions were extensive and appeared as purplish red nodules ranging in size from mung bean to small walnut.The nodules were tough and solid,smooth in surface,with infiltration while without ulceration,pruritus or tenderness.The patient developed chest tightness and pain without obvious causes,dull pain in nature and less white sputum 6 weeks before the eruption,and then was diagnosed as malignant tumors of the left lung(poorly differentiated adenocarcinoma),cT1cN3M1c stage Ⅳ B(pleura,bone).Gene tests showed that epidermal growth factor receptor(EGFR)21 exon point mutation L858r,Ros1(-),anaplastic lymphoma kinase(ALK)(-),and physical status score(PS)of 0.The treatment was Dactinib 45mg once each day,supplemented the bone preservation therapy by ibandronic acid.As the patient's condition did not significantly improve and skin nodules increased,also the abdominal B-ultrasound examination showed that multiple metastases in liver,the treatment was changed to Ectinib hydrochloride tablets(Kemena)of 125 mg 3 times a day,combined with Crizotinib capsules(Secor)of 200 mg twice a day.Unfortunately,the patient has now been lost to follow-up.

Objective To study the effects of the intelligent hearing-assistive system incorporated in Nuro-tron cochlear implants(CI),including the autonomic acoustic scene recognition(ASR),intelligent strategy config-uration as well as the objective and subjective hearing improvements on recipients.Methods ① To evaluate the per-formance of the ASR matule,in a sound-proof room,the preset five kinds of test audios,including speech,noise,speech in noise,pure music(without human voice)and non-pure Music(with human voice)were played.Each type of scenes included 6 to 9 5 min test files.The prediction accuracy and scene switching times were calculated.② In order to evaluate the noise-reduction performance of the ABeam technology in the speech enhancement module,13 Nurotron? CI recipients were recruited and their speech recognition rate when ABeam was"ON"and"OFF"with noise coming from 90°,180°or 270°were tested,individually.Also,their subjective hearing feedback was evaluated through visual analogue scale(VAS)evaluation.Results The ASR module achieved high prediction performance,with prediction accuracy 99％±4％,96％±9％,94％±12％,94％±15％,92％±13％for speech,noise,noisy speech,pure music and non-pure music,respectively.The scene transation times for each individual scene were 1.1 ±0.3,1.4±0.7,1.3±0.5,1.4±0.8 and 1.3±0.5,indicating that the prediction was also stable.When noise came from the sides and behind of recipients and speech signal from the front,the adaptive dual microphone noise re-duction algorithm ABeam significantly increased the speech recognition score(SRS)in 5 dB signal-to-noise(SNR)environment(P＜0.001),with an average increase of 15.92％.Especially when the noise came from 180 degree backward,the SRS increased 28.68％when ABeam was"0N",which was significantly higher than when ABeam was"OFF"(P＜0.01).Conclusion The intelligent hearing-assistive system can help CI recipients automatically configure appropriate SPSs under different environments,improving the speech intelligibility and hearing comfort.

The treatment of inner ear disease is developing towards local drug delivery to avoid drawbacks of systemic approach.The cochlear implants with drug delivery functions,a newly developed method of drug delivery into inner ear for treatment,has become the focus of research in recent years.In this review,we will describe recent advances in characteristics,product developments and applications of different types of drug loaded cochlear implants for local therapy.

Objective: To describe the epidemiological distribution characteristics of peripheral blood mosaic chromosomal alteration (mCA) in community adults aged 30-79 years in 10 regions of China. Methods: A total of 100 297 participants with complete baseline information (demographic characteristics, lifestyle, physical examination, etc.) and genotyping data of blood-derived DNA in ten regions of the China Kadoorie Biobank study were included. The mCAs were detected with the Mosaic Chromosomal Alterations pipeline, and logistic regression models were used to compare the differences in the detection rate of mCAs in different regions and populations. Results: A total of 5 810 mCA carriers were detected, with the detection rate of 5.8%. The standardized detection rate was 5.1%. The baseline detection rate of mCA increased with age, which were 3.4%, 5.0%, and 9.4% in those aged 30-, 51-, and >60 years, respectively (trend test P<0.001). A more significant proportion of mCAs were found in men (8.0%) than women (4.0%), as well as in urban areas (6.4%) than in rural areas (5.3%), the difference was significant (P<0.001). After adjusting for age and gender, the detection rate of mCA was higher in current smokers or people quitting smoking due to illness and people with low physical activity level, and the mCA detection rate was lower in obesy people (5.3%) than that in people with normal body weight (5.9%) (P=0.006). Conclusions: The detection rate of mCAs varied with region and population in community adults aged 30-79 years in 10 regions of China. The study results might contribute to the molecular identification of aging populations and guide precision prevention of age-related diseases such as cancers.
Adult ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Life Style ; Risk Factors ; Smoking/epidemiology* ; Aged

Objective: To verify the feasibility and accuracy of the transanal multipoint full-layer puncture biopsy (TMFP) technique in determining the residual status of cancer foci after neoadjuvant therapy (nCRT) in rectal cancer. Methods: Between April 2020 and November 2022, a total of 78 patients from the Beijing Chaoyang Hospital of Capital Medical University, the Beijing Friendship Hospital of Capital Medical University, the Qilu Hospital of Shandong University, the Zhongnan Hospital of Wuhan University with advanced rectal cancer received TMFP after nCRT participated in this prospective multicenter trial. There were 53 males and 25 females, aged (M(IQR)) 61 (13) years (range: 35 to 77 years). The tumor distance from the anal verge was 5 (3) cm (range: 2 to 10 cm). The waiting time between nCRT and TMFP was 73 (26) days (range: 33 to 330 days). 13-point transanal puncture was performed with a 16 G tissue biopsy needle with the residual lesion as the center. The specimens were submitted for independent examination and the complications of the puncture were recorded. The consistency of TMFP and radical operation specimen was compared. The consistency of TMPF with clinical remission rates for the diagnosis of complete pathological remission was compared by sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Statistical analysis between groups was performed using the χ² analysis, and a paired χ² test was used to compare diagnostic validity. Results: Before TMFP, clinical complete response (cCR) was evaluated in 27 cases. Thirty-six cases received in vivo puncture, the number of punctures in each patient was 13 (8) (range: 4 to 20), 24 cases of tumor residue were found in the puncture specimens. The sensitivity to judgment (100% vs. 60%, χ²=17.500, P<0.01) and accuracy (88.5% vs. 74.4%, χ²=5.125, P=0.024) of TMFP for the pathologic complete response (pCR) were significantly higher than those of cCR. Implement TMFP based on cCR judgment, the accuracy increased from 74.4% to 92.6% (χ²=4.026, P=0.045). The accuracy of the in vivo puncture was 94.4%, which was 83.3% of the in vitro puncture (χ²=1.382, P=0.240). Overall, the accuracy of TMFP improved gradually with an increasing number of cases (χ²=7.112, P=0.029). Conclusion: TMFP is safe and feasible, which improves the sensitivity and accuracy of rectal cancer pCR determination after nCRT, provides a pathological basis for cCR determination, and contributes to the safe development of the watch and wait policy.

Objective: To Summarize the safety, clinical outcome and technical evolution of laparoscopic gastric cancer surgery. Methods: A retrospective cohort study was carried out. Clinical data of 3012 patients who underwent laparoscopic radical gastrectomy for gastric cancer from January 2010 to March 2022 at Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University were retrospectively collected and analyzed. Case inclusion criteria were gastric malignancies confirmed by pathology, without distant metastasis by examination before operation and exploration during operation, patients undergoing laparoscopic radical gastrectomy, intact function of important organs and with complete data. Exclusion criteria were patients who underwent emergency gastric cancer resection due to gastric bleeding, perforation or obstruction, etc., tumor found to invade adjacent organs such as pancreas or transverse colon during the operation, conversion to open surgery during the operation, those who had other malignant tumors (except thyroid cancer) within 5 years, and those had severe cardiopulmonary, liver, or kidney insufficiency before surgery. Outcomes included: (1) baseline information of patients; (2) trend of the quantity of laparoscopic radical gastrectomy year by year; (3) evolution of the mode of digestive tract reconstruction; (4) periopertive outcome short-term complication was defined as complication occurring within 30 days after operation and classified accordiny to the clavien-Dindo criteria; and (5) 5-year overall survival. SPSS software was used for statistical analysis. Continuous variables that obeyed the normal distribution were expressed in the form of Mean±SD. Days of hospital stay that did not follow a normal distribution were expressed as median (Q₁,Q₃), and the Mann-Whiney U test was used for comparison. Discrete variables were expressed as cases (%), and chi-square test or rank sum test was used for comparison between groups. Linear regression analysis was used to analyze the relationship between the amount of surgery and the year of surgery. Kaplan-Meier method and log-rank test were used for survival analysis. Two-tailed P<0.05 was considered as statistically significant. Results: Among the 3012 cases, 2114 were male and 898 were female. The patients' average age at surgery was (61.1±10.7) years old. According to the number of cumulative cases, the patients were divided into three groups: early, intermediate and late, with 1004 patients in each group. The early group consisted of patients undergoing operation from January 2010 to October 2018, the intermediate group consisted of patients undergoing operation from October 2018 to January 2021, and the late group consisted of patients undergoing operation from January 2021 to March 2022. (1) General information: There were 691 (68.8%), 699 (69.6%) and 724 (72.1%) male patients in early, intermediate and late groups respectively; the average age increased from 56.6 years in 2010 to 62.8 years in March 2022. As for the tumor stage T1, T2, T3, T4, there were 49.0%, 14.4%, 23.9% and 12.6% in the early group; 47.5%, 12.9%, 26.9% and 12.6% in the intermediate group; 39.7%, 14.6%, 30.0%, and 15.6% in the late group, respectively. Patients with N0, N1, N2, N3a, N3b stage were 56.8%, 13.7%, 13.4%, 11.0%, and 5.0% in the early group; 55.7%, 12.9%, 12.8%, 11.6%, and 6.9% in the intermediate group; 51.0%, 16.1%, 12.8%, 12.5%, and 7.5% in the late group, respectively. (2) Year-by-year change in the number of gastric cancer operations: From 19 cases per year in 2010 to 786 per year in 2021, the annual number of gastric cancer operations was proportional to the year of operation (y=47.505x, R²=0.67). The proportion of patients with stage I disease showed a fluctuating downward trend over time, while the proportion of patients with stage III disease increased slightly, accounting for 34% until March 2022. (3) Evolution of digestive tract reconstruction methods: Except in 2010, the digestive tract reconstruction method of distal gastrectomy focused on Billroth-II+Braun anastomosis among patients undergoing laparoscopic gastric cancer surgery in other years, whose proportion had gradually increased from less than 20% in 2016 to about 70% after 2021; the gastrointestinal reconstruction methods after total gastrectomy had gradually increased in π anastomosis and overlap anastomosis since 2016, of which π anastomosis reached about 65% in 2019, and overlap anastomosis reached almost 30% in 2020; the anastomosis methods after proximal gastrectomy had been mainly double-channel anastomosis (54%) and esophagogastric anastomosis (30%) since 2016, and double-channel anastomosis accounted for up to 70% in 2019. (4) Operation time: The operation time of early, intermediate and late group was (193.3±49.8) min, (186.9±44.3) min and (206.7±51.4) min respectively. Intermediate group was significantly shorter than early group (t=3.005, P=0.003), while late group was significantly longer than early group (t=5.875, P<0.001) and intermediate group (t=9.180, P<0.001). (5) Postoperative hospital stay: The median length of hospital stay for gastric cancer patients in early, intermediate and late groups was 9 (8, 11) d, 8 (7, 10) d, and 8 (7.5, 10) d respectively. The postoperative hospital stay of intermediate group and late group was significantly shorter than that of early group (Z=-12.467, Z=-5.981, both P<0.001), but there was no significant difference between intermediate group and late group (Z=0.415,P=0.678). (6) Postoperative complication: The morbidity of short-term complication in early, intermediate and late group was 20.4% (205/1004), 16.2% (163/1004), and 16.2% (162/1004) respectively, and above morbidity of intermediate group and late group was significantly lower than that of early group (χ²=5.869, P=0.015; χ²=6.165, P=0.013), while there was no significant difference between intermediate group and late group (χ²=0.004,P=0.952). The morbidity of short-term complication of grade IIIor higher was 8.0% (80/1004), 7.6% (76/1004), and 4.9% (49/1004) in early, intermediate and late group respectively, and above morbidity of late group was significantly lower than that of early and intermediate group (χ²=7.965, P=0.005; χ²=6.219,P=0.013), while there was no significant difference between intermediate group and early group (χ²=0.111,P=0.739). (7) Survival analysis: The follow-up deadline for survival data was December 31, 2021, and the median follow-up time was 29.5 months. The overall 5-year survival rate of all the patients was 74.7%. The 5-year survival rates of stage I, II and III patients were 92.0%, 77.2%, and 40.3% respectively and 5-year survival rates of patients with stage IA, IB, IIA, IIB, IIIA, IIIB and IIIC were 93.2%, 87.8%, 81.1%, 72.7%, 46.2%, 37.1%, and 34.0% respectively. Conclusions: The number of laparoscopic gastric cancer operation in our center is increasing year by year. With the maturity of laparoscopic technology, the morbidity of complication in laparoscopic gastric cancer surgery is decreasing.
Aged ; Data Analysis ; Female ; Gastrectomy/methods* ; Humans ; Laparoscopy/methods* ; Male ; Middle Aged ; Retrospective Studies ; Stomach Neoplasms/surgery* ; Treatment Outcome

In this study, a novel oral drug delivery system based on linolenic acid-modified chitosan (CS-LA) micelle was developed to improve the oral bioavailability of doxorubicin (DOX), which was proven by its in vivo intestinal absorption in rats. The DOX-loaded CS-LA micelles (CS-LA@DOX) were prepared by the dialysis method. The synthesized micelle material was identified by proton nuclear magnetic resonance spectroscopy (¹H-NMR) and Fourier transform infrared spectroscopy (FT-IR). A series of the micelle properties, including particle size distribution, zeta potential, encapsulation efficiency (EE), drug loading (DL), micromorphology, polymorphy, and critical micelle concentration (CMC) were characterized or tested. The in vitro release of micelles was observed by the dialysis method, and the absorption-promoting effect of micelles was investigated by intestinal circulation experiments in rats. The animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Guilin Medical University. The results of ¹H-NMR and FT-IR showed that CS and LA were covalently bound via an amide linkage. The DOX encapsulated in the micelle core was in an amorphous state. The as-prepared micelles in the transmission electron microscope (TEM) image showed regular spherical shapes and uniform sizes with a series of excellent characteristics including (119.2 ± 2.1) nm of mean particle size [polymer dispersity index (PDI), 0.190 ± 0.08], +12.1 mV of zeta potential, (70.23 ± 0.74) % of EE, (8.77 ± 0.02) % of DL and 51.75 μg·mL^-1 of CMC. Compared with the reference, DOX hydrochloride, the proposed micelle drug delivery system showed an obvious sustained-release effect in vitro release; and enhanced drug absorption in the small intestine of rats.

Intertrochanteric fractures have become a severe public health problem in elderly patients. Proximal femoral nail anti-rotation (PFNA) is a commonly used intramedullary fixation device for unstable intertrochanteric fractures. Pelvic perforation by cephalic screw is a rare complication. We reported an 84-year-old female who fell at home and sustained an intertrochanteric fracture. The patient underwent surgery with PFNA as the intramedullary fixation device. Routine postoperative examination revealed medial migration of the helical blade that eventually caused pelvic perforation. We performed a cemented total hip arthroplasty as the savage procedure. At the latest follow-up of 12 months after total hip arthroplasty, the patient had no pain or loosening of the prosthesis in the left hip. Pelvic perforation should be considered when choosing PFNA as the intramedullary fixation device, especially in patients with severe osteoporosis wherein the helical blade can be easily inserted during the operation. The lack of devices to avoid oversliding of the helical blade in PFNA is an unreported cause of this complication and should be considered in such cases.
Aged ; Aged, 80 and over ; Bone Nails/adverse effects* ; Female ; Femur ; Fracture Fixation, Intramedullary/adverse effects* ; Hip Fractures/surgery* ; Humans ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To investigate the clinical effect of NRD assisted Ilizarov technique in the treatment of infected bone and soft tissue defect of tibia. METHODS: All 48 patients with infected bone and soft tissue defect of tibia were randomly divided into study group and control group from March 2013 to December 2020. There were 34 males and 14 females, aged from 24 to 55 years old with an average of (40.54±11.64) years old. There were 25 patients in the study group, including 17 males and 8 females, aged from 31 to 55 years old with an average of (41.36±9.69) years old. The study group were treated with NRD assisted with Ilizarov bone transport technique. There were 23 patients in control group, including 17 males and 6 females, aged from 24 to 53 years old with an average of(38.61±8.76) years old. The control group were treated with traditional bone transport technique. The curative rate, recurrence rate, incidence rate of pin track infection, time of using antibiotics, time of wound healing, time of carrying external fixation, time of bone transport, time of bone healing and postoperative function were used to evaluate the therapeutic effect of the two groups. RESULTS: The follow-up period was from 12 to 62 months with an average of (33.0±7.2) months. At the final follow-up, there was no significant difference in the curative rate between the two groups (P>0.05). The recurrence rate in the study group was lower than that in the control group(P<0.05). The incidence of pin track infection in the study group was lower than that in the control group (P<0.05). The time of using antibiotics and wound healing in the study group was shorter than that in the control group(P<0.05). There was no significant difference in the time of bone transport and carrying of external fixation between the two groups(P>0.05). There was no significant difference in bone healing and postoperative function between the two groups(P>0.05). CONCLUSION NRD assisted Ilizarov technique can achieve satisfactory results in the treatment of infected bone and soft tissue defect of tibia and shorten the treatment period and the time of using antibiotics. It is worthy of development in clinic.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Ilizarov Technique ; Tibia/surgery* ; Tibial Fractures/surgery* ; Wound Healing ; Anti-Bacterial Agents ; Treatment Outcome ; Retrospective Studies ; External Fixators