Objective: In in vitro systems for differentiating and expanding natural killer (NK) cells, feeder cells provide essential cell-cell contact and paracrine signals that drive precursor proliferation and terminal maturation. However, existing xenogeneic feeder cells or tumor-derived genetically modified feeder cells pose risks of residual immunogenicity and malignant transformation, limiting clinical use. This study aims to develop a humanized mesenchymal-like stromal cell (hematopoietic organoid-derived human mesenchymal stromal cells, HO-hMSCs) derived from iPSC-based hematopoietic organoids, and elucidate its mechanisms of NK-supportive activity to enable a safe, efficient platform for clinical-grade NK cell production. Methods: Human induced pluripotent stem cells (iPSCs) were differentiated into hematopoietic organoids, from which HO-hMSCs were isolated. Flow-cytometric phenotyping and bulk RNA-sequencing were performed to compare HO-hMSCs with umbilical cord-derived MSCs (UC-hMSCs). The effect of HO-hMSCs on NK cell differentiation efficiency (CD3 CD56 ) and effector maturation (CD16 expression) were assessed by co-culture experiments, using UC-hMSCs as control. Results: 1) Hematopoietic organoid induction and NK differentiation: iPSCs were induced to form hematopoietic organoids using cytokine cocktails, which further differentiated into high-purity CD45 CD56 NK cells [(82.8%±12.07)% efficiency on day 21]. 2) HO-hMSC characteristics: HO-hMSCs exhibited upregulated expression of Notch pathway ligands (DLL4, JAG1, 4.06-8.04-fold), homeobox genes (HOXA3, HOXA5, log FC=1.28 and 1.44), and key regulators of NK development (GATA3, BCL11A) and cytokine receptors (IL7R, IL27RA, 6.76 to 13.34-fold increase). 3) Functional validation: Compared to UC-hMSCs, HO-hMSCs co-culture significantly enhanced NK cell proportion by 30.5% (P<0.05) and increased CD16 positivity (+20.5%). Conclusion: This study for the first time reveals that human hematopoietic organoid-derived HO-hMSCs possess potent hematopoietic niche-supportive activity. It provides a humanized, feeder-free platform for robust clinical-grade NK cell production and expands the translational utility of organoid technologies in cell therapy.

Objective To investigate the application of synchronized immersion course(SIC)in teaching of clinical practice of surgery for eight-year program students.Methods A total of 94 eight-year program students in French class and 4+4 class who received SIC in the study of surgery in Ruijin Clinical School,Shanghai Jiao Tong University from September 2017 to June 2019 were selected as the pilot group.A total of 91 students in English class who were taught in the traditional way in the same period were selected as a horizontal control group.A total of 84 students in French class and 4+4 class who were studying from September 2015 to June 2017 were selected as the longitudinal control group.Teaching satisfaction evaluation,examination results and specialization choice were compared among students in each group to assess teaching effectiveness.Results The total score(3.8±0.3)and satisfaction rate(98.9%)of the questionnaire in the pilot group were better than those in the horizontal control group(3.6±0.4,90.1%)(P=0.001,P=0.008).For the case analysis station in objective structured clinical examination(OSCE),the mean score(86.2±6.9)and pass rate(97.9%)in the pilot group were better than those in the horizontal control group(79.7±11.4,89.0%)(P=0.001,P=0.014),as well as better than those in the longitudinal control group(79.5±13.5,88.1%)(P=0.001,P=0.009).For the history inquiry station,the mean score(86.3±10.7)and pass rate(96.8%)in the pilot group were better than those in the horizontal control group(81.4±11.6,86.8%)(P=0.003,P=0.013).The proportion of students choosing the surgical specialty was higher in the pilot group(55.3%)than in the horizontal control group(46.2%)and the longitudinal control group(44.0%)without statistically significant difference.Conclusions SIC can help eight-year program students strengthen their clinical thinking and practice skills.Meanwhile,SIC can increase students'satisfaction with teaching and their interest in surgery.

Objective:To investigate the feasibility of conducting active surveillance (AS) for low risk papillary thyroid microcarcinoma (PTMC) in China and to examine the factors in association with disease progression during AS.Methods:This study was a prospective observational research conducted from Jun. 2018 to Aug. 2022 at Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine. Seventy-three patients with cytologically confirmed low-risk PTMC were enrolled in this study. They were followed up by ultrasonography, and the observed nodules were re-assessed whether or not to have disease progression. Disease progression was defined as having nodule enlarged more than 3 mm in any of diameters measured on ultrasound, or/and presence of suspicious lymph node metastasis.Results:The median follow-up time was 33 months. At the time of last follow-up, 16 cases (21.9%) exhibited disease progression, including 9 cases (12.3%) with suspicious lymph nodes detected by ultrasound, and 8 cases (11.0%) with lesion enlargement; one case (1.3%) exhibited both situations. The univariate chi-square analysis revealed that young patients (≤45 years old, P=0.041), presence of microcalcifications ( P=0.032), initial larger nodule (diameter greater than 7 mm, P=0.003), and elevated thyroid autoantibody levels ( P=0.008) were associated with disease progression. Multiple regression analysis showed elevated thyroid autoantibodies ( OR=4.311, P=0.030) and initial larger nodule ( OR=6.196, P=0.034) were independent risk factors for PTMC progression,respectively. Conclusions:AS for low-risk PTMC is a feasible and effective. During the observation, ultrasound can reveal suspicious lymph nodes and nodule enlargement, which are crucial indicators for assessing disease progression. Patients with initially larger nodule size and elevated thyroid autoantibody level are more likely to exhibit disease progression and should receive closer attention.

【Objective】 To study the clinical practice and early outcome of percutaneous full-endoscopic modified posterior lumbar interbody fusion（mPLIF）combined with pedicle screw fixation through paraspinal muscle clearance. 【Methods】 A retrospective study was conducted to analyze the clinical data of patients with lower lumbar spinal diseases treated from May 2019 to April 2020. All the enrolled patients received mPLIF combined with pedicle screw fixation through paraspinal muscle clearance. The follow-up period was more than 1 year； the general parameters included age， gender， duration of disease， diagnosis of disease， surgery segment， and postoperative hospitalization time. Operation parameters included operation time and blood loss. We obtained the clinical parameters such as visual analogue scale （VAS） score for back and lower extremity， Oswestry disability index （ODI） score， and Macnab satisfaction score at the last follow-up. We evaluated the imaging parameters including intervertebral disc height， segmental lordosis angle， lumbar lordosis angle， as well as fusion outcome of patients with single segmental lumbar disease. In addition， intraoperative and postoperative complications were recorded. 【Results】 Totally 18 patients met the inclusion criteria， among whom 8 were male and 10 were female， with the average age of （53.3±8.3） years old and the average duration of disease being （28.9±36.6） months. Among them 16 patients were diagnosed as lumbar degenerative disease and the other 2 had lumbar disc infection. One patient received L3-L4 and L4-L5 intervertebral fusion； the others had one-segmental fusion， among which 11 cases were L4-L5 and 6 cases were L5-S1. The average operation time was （207.8±31.7） min， and the average blood loss was （25.6±7.8） mL， and the mean postoperative hospitalization time was （6.56±2.30） days. VAS scores of back and lower extremities at postoperative 1 week， 6 months and the last follow-up were statistically significantly improved from the preoperative scores. ODI scores at postoperative 6 months and the last follow-up were also statistically significantly improved. The rate of excellent and good according to the Macnab criteria was 94.4%. For the 17 single-level fusion patients， intervertebral height was significantly higher postoperatively and at the last follow-up compared with that of the preoperative one （P<0.05）. Segmental lordosis angle was bigger postoperatively and at the last follow-up （P>0.05）， which was not statistically significant. Lumbar lordosis angle was significantly bigger postoperatively （P<0.05） and bigger at the last follow-up， but with no statistical significance （P>0.05）. The fusion rate at the last follow-up was 88.2%. The cage broke in the process of implantation in one patient. A cage retroposition occurred in one patient at the follow-up. 【Conclusion】 Percutaneous full-endoscopic modified posterior lumbar interbody fusion combined with pedicle screw fixation through bilateral paraspinal muscle clearance by one incision showed excellent clinical outcomes in treating many kinds of lower lumbar diseases. This operation should be an excellent option for lower lumbar fusion.

Objective: To describe the epidemiological characteristics of a cluster of COVID-19 cases reported in Baodi district of Tianjin as of 18 February, 2020, which might be associated with the exposure in a local department store, and provide suggestions for prevention and control strategy development. Methods: The basic characteristics, time and area distributions, clinical manifestations, epidemiological history and transmission mode of the COVID-19 cases associated with the department store exposure were analyzed. Results: A total of 40 COVID-19 cases were associated with the department store exposure, accounting for 75.47% of the total confirmed cases (53 cases) reported in Baodi district. The cases were mainly at the age of 60 years or older (35.00%) and farmers (40.00%). The main clinical manifestations included fever (95.00%), cough (35.00%), and diarrhea (15.00%). The proportion of confirmed severe cases was 32.50%. The incidence curve showed that the incidence peak occurred on 31 January, 2020. Among the 40 cases, 6(15.00%) were department store employees, 19(47.50%) were customers and 15(37.50%) were close contacts (secondary cases). The first case occurred on 21 January, 2020, this case was a department store employee who had a purchasing history at whole sale markets in other provinces and cities before the onset, and 3 employees were still on duty after symptom onsets. The median of the incubation period of customer cases was 6 days, and the median of the interval between onset and medical treatment of customer cases was 7 days. Conclusion This was a cluster epidemic of COVID-19, which might be associated with the exposure in the department store. By now, the current prevention and control measures have achieved satisfied effects.

Objective:To observe the clinical efficacy of Ziyin-Heyang Decoction on the treatment of glucocorticoid-dependent primary immune thrombocytopenia. Methods:A total of 70 patients with ITP in Xiyuan Hospital of China Academy of Chinese Medical Sciences from November 2015 to November 2017 who met the inclusion criteria were divided into two groups according to the random number table method. 33 cases in the treatment group and 32 cases in the control group completed the reaserch. The control group received standard dose of prednisone acetate orally, and the dose was gradually reduced according to platelet count; and the treatment group was given Ziyin-Heyang Decoction on the basis of the control group. Both groups had one course of treatment for 8 weeks, with a total of 2 courses of treatment. Before and after treatment, TCM syndrome score was performed, PLT was detected by impedance method, bleeding score was calculated, daily dosage of prednisone acetate tablets was recorded, and platelet related antibodies (PAIgA, PAIgG, PAIgM, PAIgD) were detected by flow cytometry. Then clinical and syndrome efficacy were evaluated. Results:The total effective rate was 75.8% (25/33) in the treatment group and 53.1% (17/32) in the control group, and the difference in efficacy was statistically significant ( Z=2.846, P<0.05). For the TCM syndromes, the total effective rate was 100.0% (33/33) in the treatment group and 75.0% (24/32) in the control group, and there was a statistical difference between them ( Z=3.841, P<0.05). After treatment, the platelet count improvement [(97.6 ± 39.9)×10 9/L vs. (70.9 ± 16.6)×10 9/L, t=3.540] of the treatment group was significantly higher than that of the control group ( P<0.05). The TCM syndrome score [6.00 (4.00) vs. 10.00 (6.00), Z=3.510] of the treatment group was significantly lower than that of the control group ( P<0.05). After the treatment, the dose of prednisone acetate tablets [5.00 (17.50) mg/d vs. 27.66 (11.98) mg/d, Z=4.186] of the treatment group was significantly lower than that of the control group ( P<0.05). Bleeding score decreased in both groups, but there was no significant difference between them ( P>0.05). There was no statistically significant change in platelet related antibody levels in the treatment group before and after treatment ( P>0.05). Conclusions:The Ziyin-Heyang Decoction has advantages in improving platelet count, with drawing glucocorticoid and improving symptoms.

Objective:To compare the clinical effects of oblique lumbar interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) in the treatment of lumbar degenerative scoliosis.Methods:A retrospective study was performed in 116 patients with lumbar degenerative scoliosis and spinal stenosis, who were admitted to Beijing Jishuitan Hospital from January 2015 to May 2018. The patients were divided into two groups according to the surgical method. Among them, 56 patients underwent the OLIF approach (OLIF group), consisting of 21 men and 35 women, with an average age of 65.2±8.7 years. According to Lenke-Silva classification, there were 41 cases of type II and 15 cases of type III in OLIF group. 60 cases underwent the TLIF approach (TLIF group), consisting of 19 men and 41 women, with an average age of 61.3±11.6 years. There were 43 cases of type II and 17 cases of type III in TLIF group. The preoperative and last follow up visual analogue scale (VAS) and Oswestry disability index (ODI) were compared between the two groups. The coronal and sagittal Cobb angle changing and the offset distance for apical midline of the lumbar vertebrae between pre-operation and last follow-up were measured. The respective complications of the two groups were collected.Results:For OLIF group, VAS decreased from 7.7±1.6 at pre-operation to 1.9±1.5 at the last follow up; for TLIF group, VAS decreased from 8.1±1.2 at pre-operation to 2.2±0.9 at the last follow up. Although there were obvious improve for both group compared pre-operation to last follow-up, there was no significant difference between the two groups. For OLIF group, ODI decreased from preoperative 47.5%±9.1% to last follow up 22.4%±6.7%; for TLIF group, ODI decreased from preoperative 52.6%±5.8% to last follow up 25.1%±8.4%. Obvious changes were foundin both group between pre-operation and last follow up, but there was no significant difference between the two groups. For sagittal lumbar cobb angle, OLIF group changed from preoperative 8.6°±5.7° to last follow-up 23.6°±4.3°. TLIF group changed from pre-operation 9.2°±4.2° to last follow-up 21.3°±4.8°. Obvious changes were found in both group between pre-operation and last follow up, while OLIF group had better improvement than TLIF group ( P=0.01). For lumbar coronal Cobb angle, OLIF group changed from preoperative 16.4°±9.6° to last follow-up 2.8°±2.1°, and TLIF group from preoperative 15.2°±7.8° to last follow-up 6.4°±2.7°. Obvious changes were found in both group comparing pre-operation to last follow up, while OLIF group had better improvement. The offset distance for apical midline of the lumbar vertebrae in OLIF group improved from preoperative 26.3±9.4 mm to 4.3±1.9 mm; TLIF group improved from preoperative 23.4±5.5 mm to 7.5±4.2 mm. Obvious changes were found between pre-operation and last follow up for both group, while OLIF group has better improvement compared to TLIF group ( t=-5.26, P=0.03). The fusion rate was 97.7% (127/130) in OLIF group, and 91.1% (164/180) in TLIF group. There was no statistically significant difference between the two groups ( χ2=1.15, P=0.097). The neural complication rate was 16.1% (9/56) in OLIF groupand 8.3% (5/60) in TLIF group. There was no statistical difference between the two groups ( χ2=1.63, P=0.201). The cage subsidence was 12.3% (16/130) in OLIF group and 21.9% (35/180) in TLIF group. There was statistically significant difference between the two groups ( χ2=4.53, P=0.03). Conclusion:OLIF can be considered as an effectivesurgical option for the treatment of lumbar degenerative scoliosis with spinal stenosis, since it can achieve similar clinical effects and better correction of coronal and sagittal imbalances compared to TLIF.

Objective To investigate the effect of ulinastatin on postoperative clinical outcomes in pa-tients undergoing elective laparoscopic colectomy. Methods 454 patients underwent elective laparoscopic colecto-my from January 2015 to September 2017 were included in this retrospective study. Patients were divided into 2 groups:ulinastatin group and control group. Propensity score matching was applied to balance the preoperative baseline differences between 2 groups. 155 patients in each group were successfully matched. Mixed linear model was used to exam the effect of ulinastatin on various clinical indicators within 3 days after the surgery,including in-flammation indicators(white blood cell counts,C reactive protein),liver function indicators(alanine transami-nase,aspartate transaminase,total bilirubin),renal function indicators(serum creatinine,blood urea nitrogen). Postoperative hospital length of stay was compared between 2 groups using student's t-test. Results Ulinastatin group showed significantly reduced postoperative white blood cell count and ? reactive protein level (P = 0.036 and 0.025)compared with the control group. The average mean inhibitory effects were 1.04×109/L and 23.93 mg/L respectively,which was 11.1% and 29.9% lower than that of the control group. Procalcitonin,transaminases,total bilirubin,serum creatinine,blood urea nitrogen levels and postoperative hospital length of stay showed no signifi-cant difference between the two groups(P > 0.05). Conclusion Ulinastatin can significantly reduce the level of inflammation response after laparoscopic colectomy,which is beneficial to the fast recovery.

OBJECTIVETo explore the factors affecting the operative difficulty of triple-port laparoscopic surgery (TLS) in anterior resection.

METHODSA retrospective case-control study was carried out. Clinical and MRI imaging data of 106 colorectal cancer cases undergoing TLS anterior resection at Department of Colorectal Surgery of Ruijin Hospital between 2013 and 2016 were retrospectively analyzed.

INCLUSION CRITERIA(1) patients receiving TLS anterior resection (Dixon operation); (2) preoperative stageI( to III( malignant tumor;(3) distance of 5-15 cm from inferior margin of tumor to anal verge; and (4) available preoperative rectal MRI.

EXCLUSION CRITERIA(1) patients receiving preoperative adjuvant therapy; (2) patients with low rectal cancer or with local advanced disease; (3) T4b tumor. Rectal MRI was introduced to measure the structure of pelvis. In sagittal view, superior margin of the first sacral vertebrae, superior margin of the third sacral vertebrae, apex of coccyx, and the line of superior margin of pubic symphysis were used to form a pentagon. The 5 lines were marked as N, O, P, Q, R, and the 5 included angles were marked as angle 1, 2, 3, 4, 5. Organs (uterus and prostate) and tumor (transverse diameter, longitudinal diameter, section area, lesion length, distance to circumference cutting edge) were also measured on MRI. The operative time was applied to be the indicator of operative difficulty and patients were divided into 2 groups according to median operative time. Baseline information (age, gender, BMI, distance from inferior margin of tumor to anal verge, operative history, length of tumor), preoperative tumor staging, and MRI measurements (pelvis, tumor, uterus, prostate), etc were compared between two groups. Factors affecting operative difficulty of TLS were analyzed with logistic regression model.

RESULTSOf 106 enrolled patients, 73 were male and 33 female with mean age of (59.8±12.2) years and mean BMI of (22.8±3.3) kg/m; 25 patients had previous abdominal surgery; distance from inferior margin of tumor to anal verge was (7.4±2.0) cm and the tumor diameter was (3.7±1.4) cm; 24, 36 and 46 patients were in stage I(, II( and III( respectively. All operations were completed successfully. The median number of harvested lymph node was 13(11-16); the median length of distal resection margin was 2.5(2.0-3.1) cm; the median operative time was 2.0(1.5-2.6) hours; the median intraoperative blood loss was 50(0-100) ml; the median time to liquid diet was 4(3-5) days; the median hospital stay was 7(6-10) days. Ten cases (9.4%) developed complications within 30 days after surgery. Patients were divided into ≤2 h group and > 2 h group according to median operative time, and both groups had 53 patients. As compared to ≤2 h group, >2 h group had shorter distance from inferior margin of tumor to anal verge [(6.8 ± 1.5) cm vs. (8.0 ± 2.4) cm, t = 3.174, P = 0.004], lower ratio of (R+N)/(O+P)(1.61±0.27 vs. 1.73±0.19, t = 2.494, P = 0.014), larger transverse distance of tumor [(3.45±0.72) cm vs. (3.05±0.89) cm, t = 0.224, P = 0.027]. Multivariate logistic regression analysis showed the distance from inferior margin of tumor to anal verge was the independent factor affecting operative difficulty(OR=0.584, 95%CI:0.429-0.796, P = 0.001).

CONCLUSIONSSurgeons may have less difficulty in performing TLS anterior resection for patients with longer distance from inferior margin of tumor to anal verge. In preoperative assessment of operative difficulty of TLS, comprehensive evaluation should be performed. Distance from inferior margin of tumor to anal verge should be regarded as the main factor, and MRI (R+N)/(O+P) and transverse diameter of tumor should be used as important reference, leading to reasonable choice of cases for TLS and smooth pass of study curve.

Aged ; Anal Canal ; Case-Control Studies ; Female ; Humans ; Laparoscopy ; methods ; Male ; Middle Aged ; Rectal Neoplasms ; diagnostic imaging ; surgery ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo explore the protective effect of acupuncture along meridians on rats with myocardial ischemia and its effect and action mechanism on cardiomyocyte energy metabolism.

METHODSA total of 104 healthy 12-week-old SD rats were fed adaptively for 1 week and included into study with no disease symptoms observed. Of them, 24 SD rats were selected regardless of gender, and were randomly divided into a blank group and a sham operation group, 12 rats in each one. The remaining 80 SD rats were treated with ligation of left anterior descending coronary artery to establish the model of myocardial ischemia. The successful rate of model establishment was 60%, and 48 rats survived. They were randomly divided into a model group, an acupuncture along meridian group, an acupuncture along another-meridian group and a non-acupoint group, 12 rats in each one. The blank group was not treated with operation, but only bundle fixation. The sham operation group was treated with sham operation (coronary artery was not ligatured). The model group bundle fixation. The acupuncture along meridian group were treated with electroacupuncture (EA) at "Neiguan" (PC 6), the acupuncture along another-meridian group were treated with EA at "Hegu" (LI 4), and the non-acupoints group were treated at a non-acupoint which located in the hollow of the 3rd and 4th metatarsal bones of the dorsal foot of fore rate limb. Each bundle fixation or EA was given for 30 min, once a day for consecutive 5 days. The electrocardiogram was tested in all groups; the apoptosis rate of cardiomyocytes was detected by Tunel; the contents of ATP, ADP and AMP in myocardium were detected by high performance liquid chromatography.

RESULTSThe ST segment voltage after model establishment was higher than that before modeling (all<0.05). Compared with the model group after intervention, the ST segment was elevated in the acupuncture along meridian group, acupuncture along another-meridian group and non-acupoint group (<0.01,<0.05), but the apoptosis rate of cardiomyocytes was significantly reduced (all<0.01). Compared with the acupuncture along another-meridian group and non-acupoint group, the apoptosis rate of cardiomyocytes in the acupuncture along meridian group was significantly decreased (both<0.01). Compared with the model group after intervention, the content of ATP was increased in acupuncture along meridian group (<0.05); compared with the non-acupoint group, the content of ATP was increased in the acupuncture along meridian group (<0.05); compared with the model group, the contents of ADP and AMP were reduced in the acupuncture along meridian group, acupuncture along another-meridian group and non-acupoint group (all<0.05); the energy charge EC in the acupuncture along meridian group was higher than that in the model group (<0.05).

CONCLUSIONAcupuncture along meridians can effectively relieve the damage of cardiac muscle tissue; the possible mechanism is to increase ATP and reduce ADP, AMP of cardiomyocytes, so EC level is elevated and myocardial cell apoptosis is inhibited, leading to protective effect on cardiac muscle tissue and cells.