1.Single-cell RNA sequencing reveals Shen-Bai-Jie-Du decoction retards colorectal tumorigenesis by regulating the TMEM131-TNF signaling pathway-mediated differentiation of immunosuppressive dendritic cells.
Yuquan TAO ; Yinuo MA ; Limei GU ; Ye ZHANG ; Qinchang ZHANG ; Lisha ZHOU ; Jie PAN ; Meng SHEN ; Xuefei ZHUANG ; Linmei PAN ; Weixing SHEN ; Chengtao YU ; Dan DONG ; Dong ZHANG ; Tingsheng LING ; Yang SUN ; Haibo CHENG
Acta Pharmaceutica Sinica B 2025;15(7):3545-3560
Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc Min/+ mice and clinical patients. There was a marked accumulation of CCL22+ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22+ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22+ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.
2.Disease characteristics and costs of pediatric Mycoplasma Pneumoniae pneumonia hospitalization:a retrospective study at municipal hospitals from 2019 to 2023 in Shanghai
Ying-Wen WANG ; Feng WANG ; Li-Bo WANG ; Ai-Zhen LU ; Yi WANG ; Yong-Hao GUI ; Quan LU ; Yong YIN ; Jian-Hua ZHANG ; Ying-Zi YE ; Hong XU ; Bing SHEN ; Dan-Ping GU ; Xiao-Yan DONG ; Jia-Yu WANG ; Wen HE ; Xiao-Bo ZHANG
Fudan University Journal of Medical Sciences 2024;51(4):515-521
Objective To investigate disease characteristics and hospitalization costs of children with Mycoplasma Pneumoniae pneumonia(MPP)admitted to Shanghai municipal medical hospitals from 2019 to 2023.Methods Depending on the Shanghai Municipal Hospital Pediatric Alliance,we retrospectively investigated community acquired MPP pediatric patients hospitalized in 22 municipal hospitals with pediatric qualifications(including 4 children's hospitals)in Shanghai from Jan 2019 to Dec 2023.We collected the patients'diagnosis codes,gender,age,length of hospital stay,hospitalization costs,and whether they progressed to severe Mycoplasma pneumoniae pneumonia(SMPP).Results From 2019 to 2023,a total of 29 045 hospitalized children with MPP were treated,with 6 035 cases(20.8%)identified as SMPP in the 22 hospitals.Trend analysis revealed a rising trend with years in the proportion of SMPP patients(χ2trend=365.498,P<0.001).Among the 4 children's hospitals,there were 18 710 cases with MPP,including 4 078 cases(21.8%)of SMPP.The proportion of SMPP patients also showed an increasing trend with years(χ2trend=14.548,P<0.001),and the proportion in 2023(23.0%)was higher than that in previous years with statistical significance.There were statistical differences in the seasonal distribution of MPP cases between different years,with higher proportions in summer and autumn overall.The age distribution of hospitalized MPP children varied among different years,with school-age children accounting for the majority(56.8%)in 2023.There was no difference in the distribution of severe cases between different genders,but there were differences in the proportion of severe cases among different age groups in different years,with a gradual increase in severe cases among children aged 1 to 3 years(χ2trend=191.567,P<0.001).The average length of hospital stay for MPP during the epidemic was higher than that during non-epidemic periods,and there were statistically significant differences in the average length of hospital stay between different years(P<0.001).The individual hospitalization costs during the epidemic were higher than in other years,and there were statistically significant differences in individual hospitalization costs between different years(P<0.001).The total hospitalization costs were still higher in 2019 and 2023.The individual hospitalization costs for SMPP were higher than for non-SMPP cases.Conclusion MPP outbreaks occurred in Shanghai in 2019 and 2023,with the higher proportions in summer and autumn overall.Compared to previous years,the number of hospitalized MPP children in Shanghai was higher in 2023,with a higher proportion of SMPP cases,especially among children under 3 years old.The individual per capita hospitalization expenses for SMPP cases were higher than for non-SMPP cases.
3. Hippo-YAP pathway is involved in the effect of NaAsO
Song WU ; Dan GU ; Wen-Run KANG ; Yu LIU ; Cheng LI ; Hong-Jian WANG ; Dong-Yan WANG ; Ji-Gang PAN ; Xiao-Long ZHANG
Chinese Pharmacological Bulletin 2023;39(12):2325-2330
Aim To explore the effects of NaAsO
4.Hospitalization costs of pediatric community-acquired pneumonia in Shanghai.
Ying Zi YE ; Yong Hao GUI ; Quan LU ; Jian Guo HONG ; Rui FENG ; Bing SHEN ; Yue Jie ZHANG ; Xiao Yan DONG ; Ling SU ; Xiao Qing WANG ; Jia Yu WANG ; Dan Ping GU ; Hong XU ; Guo Ying HUANG ; Song Xuan YU ; Xiao Bo ZHANG
Chinese Journal of Pediatrics 2023;61(2):146-153
Objective: To investigate the epidemiology and hospitalization costs of pediatric community-acquired pneumonia (CAP) in Shanghai. Methods: A retrospective case summary was conducted on 63 614 hospitalized children with CAP in 59 public hospitals in Shanghai from January 2018 to December 2020. These children's medical records, including their basic information, diagnosis, procedures, and costs, were extracted. According to the medical institutions they were admitted, the patients were divided into the children's hospital group, the tertiary general hospital group and the secondary hospital group; according to the age, they were divided into <1 year old group, 1-<3 years old group, 3-<6 years old group, 6-<12 years old group and 12-18 years old group; according to the CAP severity, they were divided into severe pneumonia group and non-severe pneumonia group; according to whether an operation was conducted, the patients were divided into the operation group and the non-operation group. The epidemiological characteristics and hospitalization costs were compared among the groups. The χ2 test or Wilcoxon rank sum test was used for the comparisons between two groups as appropriate, and the Kruskal-Wallis H test was conducted for comparisons among multiple groups. Results: A total of 63 614 hospitalized children with CAP were enrolled, including 34 243 males and 29 371 females. Their visiting age was 4 (2, 6) years. The length of stay was 6 (5, 8) days. There were 17 974 cases(28.3%) in the secondary hospital group, 35 331 cases (55.5%) in the tertiary general hospital group and 10 309 cases (16.2%) in the children's hospital group. Compared with the hospitalizations cases in 2018 (27 943), the cases in 2019 (29 009) increased by 3.8% (1 066/27 943), while sharply declined by 76.2% (21 281/27 943) in 2020 (6 662). There were significant differences in the proportion of patients from other provinces and severe pneumonia cases, and the hospitalization costs among the children's hospital, secondary hospital and tertiary general hospital (7 146 cases(69.3%) vs. 2 202 cases (12.3%) vs. 9 598 cases (27.2%), 6 929 cases (67.2%) vs. 2 270 cases (12.6%) vs. 9 397 cases (26.6%), 8 304 (6 261, 11 219) vs. 1 882 (1 304, 2 796) vs. 3 195 (2 364, 4 352) CNY, χ2=10 462.50, 9 702.26, 28 037.23, all P<0.001). The annual total hospitalization costs of pediatric CAP from 2018 to 2020 were 110 million CNY, 130 million CNY and 40 million CNY, respectively. And the cost for each hospitalization increased year by year, which was 2 940 (1 939, 4 438), 3 215 (2 126, 5 011) and 3 673 (2 274, 6 975) CNY, respectively. There were also significant differences in the hospitalization expenses in the different age groups of <1 year old, 1-<3 years old, 3-<6 years old, 6-<12 years old and 12-18 years old (5 941 (2 787, 9 247) vs. 2 793 (1 803, 4 336) vs. 3 013 (2 070, 4 329) vs. 3 473 (2 400, 5 097) vs. 4 290 (2 837, 7 314) CNY, χ2=3 462.39, P<0.001). The hospitalization cost of severe pneumonia was significantly higher than that of non-severe cases (5 076 (3 250, 8 364) vs. 2 685 (1 780, 3 843) CNY, Z=109.77, P<0.001). The cost of patients who received operation was significantly higher than that of whom did not (10 040 (4 583, 14 308) vs. 3 083 (2 025, 4 747) CNY, Z=44.46, P<0.001). Conclusions: The number of children hospitalized with CAP in Shanghai decreased significantly in 2020 was significantly lower than that in 2018 and 2019.The proportion of patients from other provinces and with severe pneumonia are mainly admitted in children's hospitals. Hospitalization costs are higher in children's hospitals, and also for children younger than 1 year old, severe cases and patients undergoing operations.
Infant
;
Female
;
Male
;
Humans
;
Child
;
Retrospective Studies
;
China/epidemiology*
;
Hospitalization
;
Community-Acquired Infections/therapy*
;
Hospitals, Pediatric
;
Pneumonia/therapy*
5.Effectiveness of arthroscopic "hybrid" suture for delaminated rotator cuff tear: A prospective randomized controlled study.
Zhichao CHEN ; Zhiwei ZHANG ; Xie JIANG ; Yu DAN ; Zuchao GU
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(4):398-403
OBJECTIVE:
To investigate the effectiveness of "hybrid" suture with en masse combined with double-layer repair under arthroscopy in repair of delaminated rotator cuff tear by comparison with en masse suture.
METHODS:
Fifty-six patients with delaminated rotator cuff tears met selection criteria between June 2020 and January 2022 were included in the study. Patients were divided into two groups ( n=28) using a random number method. The patients in trial group underwent arthroscopic "hybrid" suture with the combination en masse and double-layer suture. The patients in control group underwent en masse suture under arthroscopy. There was no significant difference between the two groups ( P>0.05) in terms of gender, age, rotator cuff tear side, tear size, cause of injury, disease duration, and preoperative American Association of Shoulder and Elbow Surgeons (ASES) score, the University of California at Los Angeles (UCLA) shoulder scoring, visual analogue scale (VAS) score, and shoulder range of motion (forward flexion and lateral external rotation). The operation time, the difference of ASES score, UCLA score, VAS score, and shoulder range of motion (forward flexion and lateral external rotation) between pre- and post-operation were recorded and compared between the two groups ( P>0.05). The rotator cuff healing was examined by MRI and evaluated based on the classification criteria of rotator cuff healing proposed by Sugaya et al.
RESULTS:
Three cases (1 case in the trial group and 2 cases in the control group) were excluded from the study due to loss of follow-up. Twenty-seven cases in the trial group and 26 cases in the control group were included in the final study analysis. All operations of the two groups were completed successfully. There was no significant difference in the operation time between groups ( P>0.05). The follow-up time was 10-12 months (mean, 10.9 months) in the trial group and 10-13 months (mean, 11.4 months) in the control group. All incisions healed by first intention. No surgery-related complications occurred. The UCLA score, ASES score, VAS score, and shoulder range of motion (forward flexion and lateral external rotation) of both groups at 9 months after operation were significantly superior to those before operation ( P<0.05). The difference of UCLA score, ASES score, and VAS score between before and after operation in the trial group were significantly better than those in the control group ( P<0.05). There was no significant differences between the two groups in the difference of shoulder range of motion (forward flexion and lateral lateral rotation) ( P>0.05). At 9 months after operation, according to the classification criteria of rotator cuff healing proposed by Sugaya et al, MRI showed that the rotator cuff healing of the trial group was significantly better than that of the control group ( P<0.05).
CONCLUSION
Compared with en masse suture, arthroscopic "hybrid" suture for the repair of delaminated rotator cuff tear has advantages in relieving pain and improving shoulder joint function, and the rotator cuff healing is better.
Humans
;
Rotator Cuff Injuries/surgery*
;
Prospective Studies
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Shoulder Joint/surgery*
;
Treatment Outcome
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Arthroscopy/methods*
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Sutures
;
Range of Motion, Articular
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Magnetic Resonance Imaging
6.A combined regimen based on bortezomib and glucocorticoids for 6 patients with recurrent/refractory immune thrombotic thrombocytopenic purpura.
Jie YIN ; Hong TIAN ; Dan Qing KONG ; Yun LI ; Cheng Yuan GU ; De Pei WU ; Zi Qiang YU
Chinese Journal of Hematology 2023;44(5):413-417
Objective: To observe the efficacy and adverse reactions of a combination therapy regimen based on bortezomib and glucocorticoids in recurrent/refractory immune thrombocytopenic purpura (iTTP) . Methods: Six patients with recurrent/refractory TTP were included and treated with a glucocorticoid and two courses of bortezomib-based regimen. The clinical remission status of patients, changes in ADAMTS13 activity/ADAMTS13 inhibitor, and the occurrence of treatment-related adverse reactions were observed. Results: Of the 6 patients, 2 were males and 4 were females, with a median age of 21.5 (18-68) years. Refractory TTP was found in 1 case and recurrent TTP in 5 cases. Glucocorticoids were administered with reference to prednisone at 1 mg·kg(-1)·d(-1), and gradually reduced in dosage after achieving clinical remission. Bortezomib is subcutaneously administered at 1.3 mg/m(2) on days 1, 4, 8, and 11 with a 28-day treatment course consisting of 2 courses. Six patients achieved clinical remission after receiving bortezomib as the main treatment. ADMATS13 activity returned to normal in all patients with TTP after treatment, and the ADAMTS13 inhibitor turned negative. Thrombocytopenia is the most common adverse reaction after treatment, with other adverse reactions, including peripheral neuritis and abdominal pain, but ultimately all patients returned to normal. In a median follow-up of 26 (9-41) months, 5 patients maintained sustained remission, and 1 patient relapsed after 16 months of bortezomib treatment. Conclusion: Combination therapy of bortezomib and glucocorticoids has a satisfactory therapeutic effect and controllable adverse reactions for recurrent/refractory iTTP.
Male
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Female
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Humans
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Young Adult
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Adult
;
Middle Aged
;
Aged
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Bortezomib/therapeutic use*
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Glucocorticoids/therapeutic use*
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Rituximab/therapeutic use*
;
Purpura, Thrombotic Thrombocytopenic/drug therapy*
;
Purpura, Thrombocytopenic, Idiopathic/drug therapy*
;
ADAMTS13 Protein/therapeutic use*
7.Mechanism of intestinal injury induced by WNT2B high-expressed fibroblasts in Crohn's disease.
Yan Ling CHENG ; Shu Zhe XIAO ; Dan Qiong LIU ; Lan Lan GENG ; Jian Biao GU ; Rui TANG ; Lin LAN ; Yun ZHU ; Pei Yu CHEN ; Zhi Hua HE ; Si Tang GONG ; Yang CHENG
Chinese Journal of Pediatrics 2023;61(7):606-613
Objective: To explore the mechanism of intestinal tissue damage induced by macrophages activated by WNT2B high-expressed fibroblasts. Methods: This study involved biological information analysis, pathological tissue research and cell experimental research. The biological information of the colon tissue from the children with inflammatory bowel disease in previous study was analyzed again with single-cell sequencing. The pathological tissues were collected by colonoscopy from 10 children with Crohn's disease treated in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from July 2022 to September 2022. According to the findings of colonoscopy, tissues with obvious inflammation or ulceration were classified as the inflammatory group, while tissues with slight inflammation and no ulceration were classified as the non-inflammatory group. HE staining was performed to observe the pathological changes of the colon tissues. Macrophage infiltration and CXCL12 expression were detected by immunofluorescence. In terms of cell experiments, fibroblasts transfected with WNT2B plasmid or empty plasmid were co-cultured with salinomycin treated or non-treated macrophages, respectively; the expression of proteins through Wnt classical pathway were detected by western blotting. Macrophages treated with SKL2001 were used as the experimental group, and those with phosphate buffer as the control group. The expression and secretion of CXCL12 in macrophages were detected by quantitative Real-time PCR and enzyme-linked immunosorbent assay (ELISA). T-test or rank sum test were used for the comparison between groups. Results: Single-cell sequencing analysis suggested that macrophages were the main cells in inflammatory bowel disease colon tissue, and there was interaction between WNT2B high-expressed fibroblasts and macrophages. HE staining of the 10 patients ((9.3±3.8) years old, 7 males and 3 females) showed that the pathological score of colon tissue in the inflammatory group was higher than that in the non-inflammatory group (4 (3, 4) vs. 2 (1, 2) points, Z=3.05, P=0.002). Tissue immunofluorescence indicated that the number of infiltrating macrophages in the inflammatory group was significantly higher than that in the non-inflammatory group under high power field of view (72.8±10.4 vs.8.4±3.5, t=25.10, P<0.001), as well as the number of cells expressing CXCL12 (14.0±3.5 vs. 4.7±1.9, t=14.68, P<0.001). In cell experiments, western blotting suggested an elevated level of glycogen synthase kinase-3β phosphorylation in macrophages co-cultured with fibroblast transfected with WNT2B plasmid, and salinmycin could reverse this change. Real-time PCR suggested that the transcription level of CXCL12 in the experimental group was higher than that in the control group (6.42±0.04 vs. 1.00±0.03, t=183.00, P<0.001), as well as the expression and secretion of CXCL12 by ELISA ((465±34) vs. (77±9) ng/L, t=13.21, P=0.006). Conclusion: WNT2B high-expressed fibroblasts can secrete WNT2B protein and activate the Wnt classical signaling pathway thus enhancing the expression and secretion of CXCL12 in macrophages, inducing the development of intestinal inflammation of Crohn's disease.
Child
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Male
;
Humans
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Female
;
Child, Preschool
;
Adolescent
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Crohn Disease
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Inflammatory Bowel Diseases
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Colon
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Inflammation
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Colonoscopy
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Glycoproteins
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Wnt Proteins
8.Clinical research progress and implications of therapeutic vaccines for cervical cancer and precancerous lesions: a qualitative systematic review.
Shan CAI ; Ke MIAO ; Xiao Yu TAN ; Si CHENG ; Dan Tong LI ; Xue Yang ZENG ; Yu YANG ; Ruo Gu MENG ; Zhi Ke LIU ; Yan LI ; Ke Li LI ; Feng SUN ; Si Yan ZHAN
Chinese Journal of Oncology 2022;44(7):743-760
Objective: To systematically summarize and analyze the clinical research progress of therapeutic vaccines for cervical cancer or precancerous lesions. Methods: English databases (PubMed, Embase, Web of Science, Cochrane library, Proquest, and ClinicalTrails.gov) and Chinese databases (SinoMed, CNKI, WanFang, and VIP Database) were systematically searched to collect literature on therapeutic vaccines for cervical cancer or precancerous lesions from inception to February 18, 2021. After screening, we evaluated the risk of bias of included studies, and combed the basic information of the literature, research designs, information of vaccines, study patients, outcome indicators and so on, qualitatively summarized the clinical research progress. Results: A total of 71 studies were included in this systematic review, including 14 random controlled trials, 15 quasi-random controlled trials, 4 cohort studies, 1 case-control study, 34 case series studies and 3 case reports. The study patients included women aged 15~79 with cervical cancer or precancerous lesions in 18 countries from 1989 to 2021. On the one hand, there were 40 studies on therapeutic vaccines for cervical precancerous lesions (22 867 participants), involving 21 kinds of vaccines in 6 categories. Results showed 3 marketed vaccines (Cervarix, Gardasil, Gardasil 9) as adjuvant immunotherapies were significant effective in preventing the recurrence of precancerous lesions compared with the conization only. In addition, MVA E2 vaccine had been in phase Ⅲ clinical trials as a specific therapeutic vaccine, with relative literature showing it could eliminate most high-grade precancerous lesions. Therapeutic vaccines for precancerous lesions all showed good safety. On the other hand, there were 31 studies on therapeutic vaccines for cervical cancer (781 participants), involving 19 kinds of vaccines in 7categories, with none had been marketed. 25 studies were with no control group, showing the vaccines could effectively eliminate solid tumors, prevent recurrence, and prolong the median survival time. However, the vaccines effectiveness couldn't be statistically calculated due to the lack of a control group. As for the safety of therapeutic vaccines for cervical cancer, 9 studies showed that patients experienced serious adverse events after treatments, where 7 studies reported that serious adverse events occurred in patients couldn't be ruled out as the results of therapeutic vaccines. Conclusions: The literature review shows that the literature evidence for the therapeutic vaccines for cervical precancerous lesions is relatively mature compared with the therapeutic vaccines for cervical cancer. The four kinds of vaccines on the market are all therapeutic vaccines for precancerous lesions, but they are generally used as vaginal infection treatments or adjuvant immunotherapies for cervical precancerous lesions, not used for the specific treatments of cervical precancerous lesions. Other specific therapeutic vaccines are in the early stage of clinical trials, mainly phase Ⅰ/Ⅱ clinical trials with small sample size. The effectiveness and safety data are limited, and further research is still needed.
Cancer Vaccines/therapeutic use*
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Cervical Intraepithelial Neoplasia/prevention & control*
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Female
;
Humans
;
Papillomavirus Infections/prevention & control*
;
Papillomavirus Vaccines/therapeutic use*
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Precancerous Conditions/therapy*
;
Uterine Cervical Neoplasms/prevention & control*
9.Efficacy and safety of 308-nm SQ light-emitting diode light and 308-nm excimer light in the treatment of facial vitiligo: a retrospective study
Chao LUAN ; Yu HU ; Kun CHEN ; Jiaan ZHANG ; Heng GU ; Ronglin ZHANG ; Xiaohua ZHANG ; Panpan TIAN ; Yan ZHU ; Chen ZHUANG ; Dan HUANG ; Mei JU
Chinese Journal of Dermatology 2022;55(1):16-19
Objective:To compare efficacy and safety of 308-nm SQ light-emitting diode (LED) light versus 308-nm excimer light in the treatment of facial vitiligo.Methods:Patients with stable facial vitiligo were retrospectively collected from Department of Physical Therapy, Hospital of Dermatology, Chinese Academy of Medical Sciences from June 2018 to June 2020, who received treatment with 308-nm SQ LED light (LED group) or 308-nm excimer light (excimer light group). The treatment was performed once or twice a week, and patients who had received more than 8 sessions of treatment were included in the analysis of efficacy and safety. Statistical analysis was carried out by using chi-square test.Results:Totally, 68 patients with 90 lesions were enrolled into the LED group, including 36 males and 32 females, aged 25.01 ± 13.37 years; 20 patients with 28 lesions were enrolled into the excimer light group, including 13 males and 7 females, aged 27.15 ± 14.30 years. After 8 and 16 sessions of treatment, there was no significant difference in the response rate between the LED group (23.33%, 46.67%, respectively) and excimer light group (14.29%, 46.43%, χ2 = 1.05, < 0.001, respectively, both P > 0.05). During the treatment, 36 (52.94%) patients in the LED group developed persistent erythema, 17 (85%) in the excimer light group developed persistent erythema or blisters. The incidence of adverse reactions was significantly lower in the LED group than in the excimer light group ( χ2 = 16.43, P < 0.001) . Conclusion:Compared with the 308-nm excimer light, the 308-nm SQ LED light showed similar effect but higher safety for the treatment of facial vitiligo.
10.Discussion on the construction and application of hospital intelligent operation management platform
Yongqin ZHANG ; Wang JIA ; Dan GU ; Yu HUANG
Chinese Journal of Hospital Administration 2022;38(3):213-216
With the continuous promotion of the comprehensive reform of public hospitals, public hospitals urgently need to change the management mode, achieve connotative development, and seek benefits from their own management, which has become an urgent task than ever. The authors expounded the construction and application practice of the hospital intelligent operation management platform, took the information construction as a tool, built the operation data warehouse, established the department accounting model, and explored the construction path of the hospital intelligent operation management, so as to provide a reference for promoting the scientific, refined and informatization of the hospital operation management, and improving the operation management level.

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