Guangzhou Women and Children's Medical Center (GWCMC) established a Rare Disease Medical Center in December 2023 and assumed responsibility for the construction of the Guangdong Provincial Rare Disease Quality Control Center. As a national children's regional medical center and a core institution for maternal and child health in the Guangdong-Hong Kong-Macao Greater Bay Area, GWCMC leverages its disciplinary strengths in maternal and pediatric specialties, centers on the diagnosis and treatment needs of rare diseases in women and children, and carries out a systematic layout in such aspects as clinical diagnosis, treatment and service system, technical system and platforms, scientific research innovation and academic influence, talent echelon and capacity building, as well as quality control and regional collaboration. This paper reviews the development trajectory of the GWCMC Rare Disease Center, summarizes its phased experience in high-quality development, and offers reflections on future directions.

OBJECTIVE To analyze the prototype components absorbed into blood and brain of Lithocarpus litseifolius leaves， so as to provide a reference for clarifying the pharmacological material basis of its prevention and treatment of central nervous system dis eases. METHODS The ethanol extract of L. litseifolius leaves， as well as the gastric lavage fluid and perfusion solution were prepared. Using rats as subjects， plasma samples of intestinal wall metabolism， intestinal flora metabolism and hepatic metabolism were prepared via in situ intestinal perfusion and closed intestinal loop method； while comprehensive metabolic plasma samples， brain tissue samples， and cerebrospinal fluid samples were collected after intragastric administration. UPLC-HRMS technology was utilized to analyze and identify chemical components and prototype components absorbed into blood and brain of L. litseifolius leaves. RESULTS A total of 66 chemical constituents were identified in L. litseifolius leaves， primarily consisting of flavonoids， organic acids， and others. A total of 16， 13， 11， and 5 prototype components were identified in intestinal wall metabolism， intestinal flora metabolism， hepatic metabolism， and comprehensive metabolic plasma samples， respectively. Additionally， 4 prototype components were detected in brain tissue and 9 in cerebrospinal fluid. Phloridzin， trilobatin， phloretin-2- O -malonyl hexoside， and phloretin were identified as common components across all sample types. CONCLUSIONS Prototype components absorbed into blood and brain of L. litseifolius leaves， such as phloridzin， trilobatin， phloretin， and other components may serve as the pharmacological material basis for their therapeutic effects on central nervous system diseases.

OBJECTIVE To investigate the impact of Netupitant and palonosetron hydrochloride capsules （NEPA） on the pharmacokinetics of Paclitaxel for injection （albumin bound） （i. e. albumin-bound paclitaxel） under different intestinal microenvironment conditions. METHODS Male SD rats were divided into a normal group and a model group （n＝16）. Rats in the model group were intragastrically administered vancomycin solution to establish an intestinal disorder model. The next day after modeling， intestinal microbiota diversity was analyzed， and the mRNA expressions of cytochrome P450 3A1 （CYP3A1） and CYP2C11 in small intestine and liver tissues as well as those protein expressions in liver tissue were measured. Male SD rats were grouped as described above （n＝16）. The normal group was subdivided into the TP chemotherapy group （TP-1 group） and the TP chemotherapy+NEPA group （TP+NEPA-1 group）； the model group was subdivided into the TP chemotherapy group （TP-2 group） and the TP chemotherapy+NEPA group （TP+NEPA-2 group） （n＝8）. Rats in the TP+NEPA-1 and TP+NEPA-2 groups received a single intragastric dose of NEPA suspension （25.8 mg/kg， calculated by netupitant）. One hour later， all four groups received a single tail vein injection of albumin-bound paclitaxel and cisplatin. Blood samples were collected at different time points after the last administration. Using azithromycin as the internal standard， plasma paclitaxel concentrations were determined by liquid chromatography-tandem mass spectrometry. The main pharmacokinetic parameters were calculated using DAS 2.0 software and compared between groups. RESULTS Compared with the normal group， the model group showed significantly decreased Chao1 and Shannon indexes （P＜0.05）， significant alterations in microbiota composition and relative abundance， and significantly downregulated expressions of CYP3A1 mRNA in liver tissue and CYP2C11 mRNA in both small intestine and liver tissues （P＜0.05）. Compared with the TP-1 group， the AUC0－t， AUC0－∞， MRT0－t of paclitaxel in the TP-2 group， the cmax， AUC0－t， AUC0－∞ of paclitaxel in the TP+NEPA-1 group and TP+NEPA-2 group were significantly increased or prolonged； CL of paclitaxel in the TP-2 group， Vd and CL of paclitaxel in the TP+NEPA-1 group and the TP+NEPA-2 group were significantly decreased or shortened （P＜0.05）. Compared with the TP-2 group， cmax of paclitaxel in the TP+NEPA-2 group was significantly increased， and Vd and MRT0－t were significantly decreased or shortened （P＜0.05）. CONCLUSIONS Intestinal microbiota disorder affects the mRNA expressions of CYP3A1 and CYP2C11， leading to decreased clearance and increased systemic exposure of paclitaxel. Concomitant administration of NEPA under normal intestinal microbiota condition increases paclitaxel exposure. However， under conditions of intestinal microbiota disorder， concomitant administration of NEPA has a limited impact on paclitaxel systemic exposure.

Objective To systematically evaluate the efficacy and safety of proximal gastrectomy (PG) versus total gastrectomy (TG) for the treatment of Siewert type Ⅱ/Ⅲ adenocarcinoma of the esophagogastric junction (AEG). Methods PubMed, The Cochrane Library, Web of Science, EMbase, CNKI, Wanfang, and VIP databases were searched for literature comparing the efficacy and safety of PG and TG for the treatment of Siewert type Ⅱ/Ⅲ AEG. The search period was from database inception to March 2023. Meta-analysis was performed using Review Manager 5.4 software. Results A total of 23 articles were included, including 16 retrospective cohort studies, 5 prospective cohort studies, and 2 randomized controlled trials. The total sample size was 2 826 patients, with 1 389 patients undergoing PG and 1 437 patients undergoing TG. Meta-analysis results showed that compared with TG, PG had less intraoperative blood loss [MD=−19.85, 95%CI (−37.20, −2.51), P=0.02] and shorter postoperative hospital stay [MD=−1.23, 95%CI (−2.38, −0.08), P=0.04]. TG had a greater number of lymph nodes dissected [MD=−6.20, 95%CI (−7.68, −4.71), P<0.001] and a lower incidence of reflux esophagitis [MD=3.02, 95%CI (1.24, 7.34), P=0.01]. There were no statistically significant differences between the two surgical approaches in terms of operative time, postoperative survival rate (1-year, 3-year, 5-year), and postoperative overall complications (P>0.05). Conclusion PG has advantages in terms of intraoperative blood loss and postoperative hospital stay, while TG has advantages in terms of the number of lymph nodes dissected and the incidence of reflux esophagitis. There is no significant difference in long-term survival between the two surgical approaches.

OBJECTIVE: The self-defined multidisciplinary (endocrinology, vascular surgery, and orthopedics) scoring system (EMO scoring system for short) was designed. The feasibility of the EMO scoring system to guide the proximal tibial transverse transport (TTT) for diabetic foot wounds was preliminarily explored. METHODS: Based on the current commonly used clinical criteria for diabetic foot judgment, expert consensus, guidelines, and related research progress in the treatment of diabetic foot wounds, combined with clinical experience, a set of EMO scoring systems including endocrinology, vascular surgery, and orthopedics was formulated. The criteria for selecting conservative treatment, TTT after baseline improvement, and TTT based on scoring results was proposed. A total of 56 patients with diabetic foot wounds who were admitted between September 2017 and July 2022 and met the selection criteria was taken as the study subjects. Among them, 28 patients were treated with TTT and 28 patients were treated conservatively. The patients were graded according to the EMO scoring system, the corresponding treatment methods were selected, and the actual treatment methods and results of the patients were compared. RESULTS: The EMO scoring system was formed through literature retrieval and clinical experiences. The system included three criteria, namely endocrinology (E), macrovascular disease (M), and orthopedics (O), which were divided into multiple subtypes according to the relevant evaluation items, and finally the diabetic foot wound was divided into 8 types, which correspondingly selected TTT, TTT after baseline improvement, and conservative treatment. All 56 patients were followed up 12 months after treatment. Among them, the wound healing rate of the TTT group was 85.71% (24/28), which was higher than that of the conservative treatment group [53.57% (15/28)]. At 12 week after treatment, CT angiography showed that there were more small blood vessels in the wound and ipsilateral limb in TTT group than in the conservative treatment group. Based on the EMO scoring system, 14 of the 56 patients needed conservative treatment, 29 patients needed TTT, and 13 patients needed TTT after baseline improvement. Compared with the clinical data of the patients, the wound healing rate of the patients judged to be TTT was 75.86% (22/29), of which 21 cases were actually treated with TTT, and the healing rate was 90.48%; 8 patients were treated conservatively, and the healing rate was 37.50%. The wound healing rate of the patients judged to be conservative treatment was 92.86% (13/14), of which 1 case was actually treated with TTT, and the healing rate was 100%; 13 cases were treated conservatively, and the healing rate was 92.31%; 1 case experienced minor amputation. The wound healing rate of the patients judged to TTT after baseline improvement was only 30.77% (4/13), of which 6 cases were actually treated with TTT, and the healing rate was 66.67%; 7 cases were treated conservatively, and the healing rate was 0. CONCLUSION EMO scoring system can comprehensively evaluate the diabetic foot wounds, and make personalized judgment on whether TTT treatment is feasible, so as to improve the level of diabetic foot wound treatment and the prognosis of patients.
Humans ; Diabetic Foot/therapy* ; Feasibility Studies ; Male ; Female ; Middle Aged ; Aged ; Tibia/surgery* ; Wound Healing ; Adult ; Treatment Outcome ; Conservative Treatment

BACKGROUND: Ferroptosis-related genes play a crucial role in regulating intracellular iron homeostasis and lipid peroxidation, and they are involved in the regulation of tumor growth and drug resistance. The expression of ferroptosis-related genes in tumor tissues can be used to predict patients' future survival times, aiding doctors and patients in anticipating disease progression. Based on the sequencing data of lung adenocarcinoma (LUAD) patients from The Cancer Genome Atlas (TCGA) database, this study identified genes involved in the regulation of ferroptosis, constructed a prognostic model, and evaluated the predictive performance of the model. METHODS: A total of 1467 ferroptosis-related genes were obtained from the GeneCards database. Gene expression profiles and clinical data from 541 LUAD patients were collected from the TCGA database. The expression data of all ferroptosis-related genes were extracted, and differentially expressed genes were identified using R software. Survival analysis was performed on these genes to screen for those with prognostic value. Subsequently, a prognostic risk scoring model for ferroptosis-related genes was constructed using LASSO regression model. Each LUAD patient sample was scored, and the patients were divided into high-risk and low-risk groups based on the median score. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated. Kaplan-Meier survival curves were generated to assess model performance, followed by validation in an external dataset. Finally, univariate and multivariate Cox regression analyses were conducted to evaluate the independent prognostic value and clinical relevance of the model. RESULTS: Through survival analysis, 121 ferroptosis-related genes associated with prognosis were initially identified. Based on this, a LUAD prognostic risk scoring model was constructed using 12 ferroptosis-related genes (ALG3, C1QTNF6, CCT6A, GLS2, KRT6A, LDHA, NUPR1, OGFRP1, PCSK9, TRIM6, IGF2BP1 and MIR31HG). The results indicated that patients in the high-risk group had significantly shorter survival time than those in the low-risk group (P<0.001), and the model demonstrated good predictive performance in both the training set (1-yr AUC=0.721) and the external validation set (1-yr AUC=0.768). Risk scores were significantly associated with the prognosis of LUAD patients in both univariate and multivariate Cox regression analyses (P<0.001), suggesting that this score is an important prognostic factor for LUAD patients. CONCLUSIONS This study successfully established a LUAD risk scoring model composed of 12 ferroptosis-related genes. In the future, this model is expected to be used in conjunction with the tumor-node-metastasis (TNM) staging system for prognostic predictions in LUAD patients.
Humans ; Ferroptosis/genetics* ; Prognosis ; Adenocarcinoma of Lung/pathology* ; Lung Neoplasms/pathology* ; Male ; Female ; Gene Expression Regulation, Neoplastic ; Middle Aged ; ROC Curve

Objective To observe the changes in the serum level of tumor necrosis factor-α(TNF-α)during pegylated interferon-alpha(PEG-IFN-α)treatment in inactive HBsAg carriers(IHCs),to investigate the association between the dynamic changes of TNF-α and HBsAg clearance,and to assess the value of TNF-α as a potential biomarker for predicting the therapeutic efficacy of PEG-IFN-α.Methods A prospective study was conducted among 455 IHCs who attended our hospital from January 2018 to March 2023,and they were divided into treatment group and IHC control group.The 210 IHCs in the treatment group voluntarily received PEG-IFNα-2b treatment for 48 weeks,followed by follow-up for 24 weeks,and the 245 IHCs in the IHC control group were followed up for 72 weeks without treatment.The serum level of TNF-α was measured at baseline(week 0)and at weeks 12,24,48,and 72,and at week 72,the treatment group was further divided into HBsAg clearance group and non-clearance group.The serum level of TNF-α at different time points was compared between groups.The logistic regression analysis was used to assess the value of TNF-α in predicting HBsAg clearance.The t-test was used for comparison of normally distributed continuous data between two groups,and a one-way analysis of variance used for comparison between multiple groups;the repeated measures analysis of variance was used for comparison of normally distributed repeated measurement data within each group and between groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Univariate and multivariate logistic regression analyses were used to investigate the predictive factors for HBsAg clearance,and the receiver operating characteristic(ROC)curve was used to determine the cut-off value of TNF-α in predicting HBsAg clearance.Results At week 72,compared with the IHC control group,the treatment group had significantly higher HBsAg clearance rate(46.2%vs 1.2%,χ2=133.333,P<0.001)and seroconversion rate(34.8%vs 0.8%,χ2=94.650,P<0.001).The HBsAg clearance group and the non-clearance group had a significant increase in the serum level of TNF-α during treatment,which gradually returned to the baseline level after drug withdrawal(F=351.733 and 76.434,both P<0.001).Comparisons between groups showed that the HBsAg clearance group had the highest serum level of TNF-α at weeks 12,24,and 48,followed by the non-clearance group and the IHC control group(all P<0.001).The multivariate logistic regression analysis showed that baseline HBsAg level(odds ratio[OR]=0.329,95%confidence interval[CI]:0.189-0.571,P<0.001),baseline HBV DNA<20 IU/mL(OR=1.414,95%CI:1.057-1.787,P=0.045),ALT≥2×upper limit of normal at week 12(OR=1.127,95%CI:1.028-1.722,P=0.043),TNF-α level at week 12(OR=1.336,95%CI:1.018-1.754,P=0.037),and TNF-α level at week 24(OR=1.879,95%CI:1.477-2.391,P<0.001)were independent predictive factors for HBsAg clearance.The ROC analysis showed that TNF-α level at week 12 had an area under the ROC curve(AUC)of 0.846(95%CI:0.814-0.889)in predicting HBsAg clearance at week 72,with a sensitivity of 76.3%and a specificity of 81.0%,while TNF-α level at week 24 had an AUC of 0.912(95%CI:0.758-0.972),with a sensitivity of 81.4%and a specificity of 96.2%.Conclusion PEG-IFN-α can increase the serum level of TNF-α in IHCs,and the serum level of TNF-α at weeks 12 and 24 can effectively predict HBsAg clearance induced by PEG-IFN-α.

Objective:To analyze the clinical efficacy of the pelvic unlocking reduction device in assisting closed reduction and internal fixation for the treatment of AO/OTA 61-C3 type pelvic fractures.Methods:A retrospective analysis was conducted on 27 patients with AO/OTA 61-C3 pelvic fractures treated with the pelvic unlocking reduction device-assisted reduction and internal fixation between January 2020 and January 2024 in Fourth Medical Center of the People's Liberation Army General Hospital. The cohort included 11 males and 16 females, with a mean age of 30.2±13.9 years (range, 13-55 years). The time from injury to surgery was 16.0 (10.0, 28.0) d (range, 6-175 d). According to the AO/OTA classification, there were 8 cases of type 61-C3.1, 10 cases of type C3.2, and 9 cases of type C3.3. Among them, 10 patients presented with associated lumbosacral nerve injuries, classified as Gibbons grade II in 5 cases, grade III in 1 case, and grade IV in 4 cases. All patients underwent closed reduction and internal fixation assisted by the pelvic unlocking reduction device. Postoperative outcomes were assessed using the visual analogue scale (VAS) for pain, the Majeed pelvic score, and the Harris hip score. Fracture reduction quality was evaluated using the Matta criteria, and overall health status was assessed using the 36-Item Short Form Health Survey (SF-36).Results:All patients successfully underwent the surgery and were followed up for 31.6±12.3 months (range, 12-48 months). The fracture reduction time was 33.45±12.18 min, the total operative time was 283.0±87.9 min, the number of fluoroscopies was 71.33±32.77, and the intraoperative blood loss was 314.1±252.6 ml. At the 12-month postoperative assessment, VAS score was 1.78±0.85, Majeed pelvic score was 87.52±15.03; SF-36 score was 88.93±11.27; and Harris Hip Score was 90.59±11.43. All patients achieved an "excellent" rating according to the Matta radiographic assessment criteria at 12 months postoperatively. Fracture union was confirmed in all cases, with a healing time of 2.9±0.4 months (range, 2.5-3.5 months). No postoperative complications such as shock, nonunion, delayed union, surgical site infection, implant loosening, or deep vein thrombosis were observed. Three patients experienced numbness in the lateral thigh region postoperatively, which was attributed to lateral femoral cutaneous nerve injury. The symptoms resolved completely following removal of the INFIX internal fixator.Conclusion:The pelvic unlocking reduction device-assisted closed reduction and internal fixation demonstrates safety and efficacy in treating AO/OTA 61-C3 type pelvic fractures, yielding satisfactory fracture union and early functional scores.

Objective:To compare the clinical efficacy of autologous bone grafting or bioceramic bone grafting combined with locking compression plate (LCP) internal fixation in the treatment of Schatzker type II and III tibial plateau fractures.Methods:A retrospective analysis was conducted on 104 patients with Schatzker type II and III tibial plateau fractures who underwent surgical treatment at the Department of Orthopedics, PLA Central Theater Command General Hospital from January 2010 to December 2021. The cohort comprised 55 males and 49 females, with an average age of 49.13±13.80 years (range 18-73 years). All fractures were unilateral: 55 on the left and 49 on the right. According to the Schatzker classification, 59 were Type II and 45 were Type III. Causes of injury included traffic accidents (48 cases), falls from height (3 cases), sprains or falls (45 cases), and other causes (8 cases). During surgery, bioceramic material or allograft bone tissue was implanted into the collapsed tibial plateau region to restore articular surface flatness. Based on graft type, patients were divided into the allograft bone group (63 cases) and the bioceramic group (41 cases). All cases underwent proximal lateral tibial LCP internal fixation. The two groups were compared in terms of operative time, intraoperative blood loss, bone graft volume, length of hospital stay, fracture healing time, and postoperative complications. The Rasmussen radiographic collapse score was used to evaluate fracture reduction, and the Hospital for Special Surgery (HSS) score system was used to assess knee joint function.Results:All patients were followed up for 12(12, 13) months (range 12-16 months). The fracture healing time in the allograft bone group was 13.70±1.36 weeks (range 11-16 weeks), which was significantly shorter than that in the bioceramic group: 14.59±1.73 weeks (range 11-19 weeks) ( t=2.911, P=0.004). The time to full weight-bearing in the allograft group was 15.0(14.0, 17.0) weeks (range 13-23 weeks), which was shorter than the 16.0 (15.5, 18.5) weeks (range 12-24 weeks) in the bioceramic group, showing a statistically significant difference ( Z=-3.019, P=0.002). At 12 months postoperatively, the Rasmussen radiographic collapse score was 1(0, 1) in the bioceramic group, significantly lower than the 1(1, 2) score in the allograft group ( Z=-2.083, P=0.037). No statistically significant differences were observed between the two groups in bone graft volume, surgical duration, intraoperative blood loss, hospitalization duration, or HSS scores at 6 and 12 months postoperatively ( P>0.05). The complication rate was 6.3% (4/63) in the allograft group and 2.4% (1/41) in the bioceramic group, with no statistically significant difference (χ 2=0.830, P=0.362). Conclusions:For Schatzker type II and III tibial plateau fractures, the use of allograft bone or bioceramic combined with LCP internal fixation can achieve good results. Allograft bone has advantages in terms of fracture healing speed and early weight-bearing recovery, while bioceramic is more effective in maintaining joint surface stability.

Fecal microbiota transplantation (FMT) has the potential to rebuild the intestinal microbiome of patients, which can influence the disease course, alleviate symptoms, or even cure the disease. It is seen as a promising breakthrough for treating major chronic diseases that are difficult to manage. Currently, FMT therapy has been clinically studied for over 80 diseases and has led to significant breakthroughs. However, there are still four main challenges: (1) identifying the effective characteristics of donor microbiota and ensuring precise matching between donors and recipients; (2) understanding the pathways and molecular mechanisms by which key FMT bacteria and metabolites improve disease outcomes; (3) studying strain interactions and colonization mechanisms to restore intestinal microbiota balance; and (4) refining the precision of microbiome and functional microbiota transplantation. To address these clinical challenges, this article reviews the latest research both domestically and internationally, outlines the response patterns of FMT therapy, examines the reasons behind FMT failure, and explores future directions for the development of FMT. The aim is to accelerate the scientific and precise advancement of FMT technology in China.