Rare diseases pose significant diagnostic and therapeutic challenges,carrying a high disease burden,their management critically reflects a nation's public health resilience.Currently,China faces key challenges such as scarce treatments,fragmented services,and low drug accessibility in rare disease care,which urgently require systemic solutions.Digital-intelligent technology as a key breakthrough are expected to resolve the challenges in this field.Although its application in the field of rare diseases is gradually expanding,there is a lack of systematic compilation of studies to elucidate how to precisely enhance the precision,synergy and sustainability of diagnosis and treatment.The key challenges in rare disease care concentrate in four areas:inefficiency in prenatal screening,uneven distribution of medical resources,low efficiency in social organization collaboration,and ineffective information dissemination.The"4C"strategy,based on digital-intelligent technology,can address these issues:①coordination,boost prenatal screening awareness and capacity via digital-intelligent platforms to strengthen prevention;②cooperation,deepen collaboration within specialist networks,empowering institutions to enhance diagnostic capacity;③co-creation,empower support organizations to optimize resources,efficiency;④cognition,minimize information dissipation through efficient platforms,improving patient and family quality of life.This establishes an integrated digital-intelligent rare disease model encompassing"screening-diagnosis-treatment-care".

Rare diseases pose significant diagnostic and therapeutic challenges,carrying a high disease burden,their management critically reflects a nation's public health resilience.Currently,China faces key challenges such as scarce treatments,fragmented services,and low drug accessibility in rare disease care,which urgently require systemic solutions.Digital-intelligent technology as a key breakthrough are expected to resolve the challenges in this field.Although its application in the field of rare diseases is gradually expanding,there is a lack of systematic compilation of studies to elucidate how to precisely enhance the precision,synergy and sustainability of diagnosis and treatment.The key challenges in rare disease care concentrate in four areas:inefficiency in prenatal screening,uneven distribution of medical resources,low efficiency in social organization collaboration,and ineffective information dissemination.The"4C"strategy,based on digital-intelligent technology,can address these issues:①coordination,boost prenatal screening awareness and capacity via digital-intelligent platforms to strengthen prevention;②cooperation,deepen collaboration within specialist networks,empowering institutions to enhance diagnostic capacity;③co-creation,empower support organizations to optimize resources,efficiency;④cognition,minimize information dissipation through efficient platforms,improving patient and family quality of life.This establishes an integrated digital-intelligent rare disease model encompassing"screening-diagnosis-treatment-care".

BACKGROUND:Human umbilical cord mesenchymal stem cell-derived exosomes are involved in multiple injury repair processes,and the effects and the specific mechanisms of renal ischemia/reperfusion injury have not been fully elucidated.OBJECTIVE:To investigate the molecular mechanism of human umbilical cord mesenchymal stem cell-derived exosomes in the treatment of renal ischemia/reperfusion injury.METHODS:(1) Human umbilical cord mesenchymal stem cells were cultured and exosomes were obtained and identified using an exosome extraction kit.(2) The distribution of exosomes in the kidney of mice with renal ischemia/reperfusion injury was examined by intravital fluorescence imaging.(3) Thirty C57/BL6 male mice were divided into five groups according to the random number table method:sham operation group,renal ischemia/reperfusion group,sham operation group+Compound C group,renal ischemia/reperfusion+exosome group (exosome group),and renal ischemia/reperfusion+exosome+Compound C group (exosome+Compound C group),with 6 mice in each group.Except the sham operation group,bilateral renal pedicles were clamped for 45 minutes and a mouse model of renal ischemia/reperfusion injury was established after 24 hours of reperfusion.In sham operation+Compound C group and exosome+Compound C group,AMPK inhibitor Compound C was intraperitoneally injected 30 minutes before model establishment.In the exosome group and exosome+Copmpound C group,exosomes were injected through the tail vein 15 minutes before renal pedicle clipping.The levels of serum creatinine and urea nitrogen,interleukin 6,and tumor necrosis factor α in renal tissue,and the expression of apoptosis-related factors in renal tissue were detected after 24 hours of reperfusion in each group.RESULTS AND CONCLUSION:(1) Human umbilical cord mesenchymal stem cell exosomes had the typical tea tray morphology,with the diameter distribution in the range of 40-160 nm,and expressed the specific marker membrane protein of exosome surface.(2) Murine kidneys after renal ischemia/reperfusion injury were more likely to gather human umbilical cord mesenchymal stem cell exosomes compared with the sham operation group.(3) Exosome pretreatment reduced renal injury and the level of renal cell apoptosis in mice treated with renal ischemia/reperfusion injury.Moreover,this protective effect could be reversed by AMPK inhibitors.These findings verify that human umbilical cord mesenchymal stem cell-derived exosomes exerting a protective effect on renal ischemia/reperfusion injury may be related to the activation of the AMPK/YAP1 pathway to antiapoptosis.

Objective:To investigate the feasibility and safety of laparoscopic purse- string suture clamps combined with multi-functional seal caps for esophagojejunal Roux-en-Y anastomosis during total laparoscopic radical total gastrectomy (TLTG).Methods:This was a retrospective descriptive study of 42 patients with primary gastric malignancies who underwent TLTG at the First Affiliated Hospital of Nanjing Medical University that utilized laparoscopic purse-string suture clamps and multi-functional seal caps for esophagojejunal anastomosis between May, 2024 and January, 2025. The cohort included 33 males and 9 females, with a mean age of (67.7 ±9.5) years and a mean body mass index (BMI) of (23.9±2.9) kg/m 2. The American Society of Anesthesiologists (ASA) physical status classifications were I - II in 40 patients and III in 2 patients, and all patients were definitively diagnosed preoperatively via gastroscopy, dual-energy CT, and/or MRI. Tumor locations included the gastroesophageal junction (GEJ) in 28 cases (Siewert type II - III), the upper third of the stomach in 12 cases, and the middle third in 2 cases. The median distance of esophageal invasion was 1.3 cm, though in 10 cases this was ≥2 cm. Preoperative TNM staging was I-II in 17 patients and III in 25 patients. Surgical outcomes including operative time, anastomosis time, intraoperative blood loss, pathological results, and postoperative recovery were retrospectively analyzed. Results:All 42 operations were successful. The mean operative time was(212.5±26.4) minutes, and the average time from multi-functional seal cap placement to completion of the esophagojejunal anastomosis was (54.2±7.5) minutes. Mean intraoperative blood loss was (79.9±21.3) ml. Postoperative pathology confirmed R0 resection in all specimens, with a mean proximal esophageal margin distance of (2.1±1.6) cm. Furthermore, (51.9±15.1) lymph nodes on average were harvested from each patient; the mean time to oral intake was (149.5±41.4) hours; and the mean hospital stay was (11.3±5.4) days. Postoperative complications occurred in 6 patients: anastomotic leakage ( n=2), residual intra-abdominal infection ( n=1), pulmonary infection ( n=3), and Clavien-Dindo grade III or higher complications occurred in 2 patients. No recurrence, mortality, or anastomosis-related complications were observed within a median follow-up of 5.8 months (range 3.5-11.2). Conclusion:We find the application of the laparoscopic purse-string suture clamps and multi-functional seal caps for esophagojejunal anastomosis in TLTG to be safe and feasible, with satisfactory short-term outcomes.

Objective:To investigate the feasibility and safety of laparoscopic purse- string suture clamps combined with multi-functional seal caps for esophagojejunal Roux-en-Y anastomosis during total laparoscopic radical total gastrectomy (TLTG).Methods:This was a retrospective descriptive study of 42 patients with primary gastric malignancies who underwent TLTG at the First Affiliated Hospital of Nanjing Medical University that utilized laparoscopic purse-string suture clamps and multi-functional seal caps for esophagojejunal anastomosis between May, 2024 and January, 2025. The cohort included 33 males and 9 females, with a mean age of (67.7 ±9.5) years and a mean body mass index (BMI) of (23.9±2.9) kg/m 2. The American Society of Anesthesiologists (ASA) physical status classifications were I - II in 40 patients and III in 2 patients, and all patients were definitively diagnosed preoperatively via gastroscopy, dual-energy CT, and/or MRI. Tumor locations included the gastroesophageal junction (GEJ) in 28 cases (Siewert type II - III), the upper third of the stomach in 12 cases, and the middle third in 2 cases. The median distance of esophageal invasion was 1.3 cm, though in 10 cases this was ≥2 cm. Preoperative TNM staging was I-II in 17 patients and III in 25 patients. Surgical outcomes including operative time, anastomosis time, intraoperative blood loss, pathological results, and postoperative recovery were retrospectively analyzed. Results:All 42 operations were successful. The mean operative time was(212.5±26.4) minutes, and the average time from multi-functional seal cap placement to completion of the esophagojejunal anastomosis was (54.2±7.5) minutes. Mean intraoperative blood loss was (79.9±21.3) ml. Postoperative pathology confirmed R0 resection in all specimens, with a mean proximal esophageal margin distance of (2.1±1.6) cm. Furthermore, (51.9±15.1) lymph nodes on average were harvested from each patient; the mean time to oral intake was (149.5±41.4) hours; and the mean hospital stay was (11.3±5.4) days. Postoperative complications occurred in 6 patients: anastomotic leakage ( n=2), residual intra-abdominal infection ( n=1), pulmonary infection ( n=3), and Clavien-Dindo grade III or higher complications occurred in 2 patients. No recurrence, mortality, or anastomosis-related complications were observed within a median follow-up of 5.8 months (range 3.5-11.2). Conclusion:We find the application of the laparoscopic purse-string suture clamps and multi-functional seal caps for esophagojejunal anastomosis in TLTG to be safe and feasible, with satisfactory short-term outcomes.

BACKGROUND:Human umbilical cord mesenchymal stem cell-derived exosomes are involved in multiple injury repair processes,and the effects and the specific mechanisms of renal ischemia/reperfusion injury have not been fully elucidated.OBJECTIVE:To investigate the molecular mechanism of human umbilical cord mesenchymal stem cell-derived exosomes in the treatment of renal ischemia/reperfusion injury.METHODS:(1) Human umbilical cord mesenchymal stem cells were cultured and exosomes were obtained and identified using an exosome extraction kit.(2) The distribution of exosomes in the kidney of mice with renal ischemia/reperfusion injury was examined by intravital fluorescence imaging.(3) Thirty C57/BL6 male mice were divided into five groups according to the random number table method:sham operation group,renal ischemia/reperfusion group,sham operation group+Compound C group,renal ischemia/reperfusion+exosome group (exosome group),and renal ischemia/reperfusion+exosome+Compound C group (exosome+Compound C group),with 6 mice in each group.Except the sham operation group,bilateral renal pedicles were clamped for 45 minutes and a mouse model of renal ischemia/reperfusion injury was established after 24 hours of reperfusion.In sham operation+Compound C group and exosome+Compound C group,AMPK inhibitor Compound C was intraperitoneally injected 30 minutes before model establishment.In the exosome group and exosome+Copmpound C group,exosomes were injected through the tail vein 15 minutes before renal pedicle clipping.The levels of serum creatinine and urea nitrogen,interleukin 6,and tumor necrosis factor α in renal tissue,and the expression of apoptosis-related factors in renal tissue were detected after 24 hours of reperfusion in each group.RESULTS AND CONCLUSION:(1) Human umbilical cord mesenchymal stem cell exosomes had the typical tea tray morphology,with the diameter distribution in the range of 40-160 nm,and expressed the specific marker membrane protein of exosome surface.(2) Murine kidneys after renal ischemia/reperfusion injury were more likely to gather human umbilical cord mesenchymal stem cell exosomes compared with the sham operation group.(3) Exosome pretreatment reduced renal injury and the level of renal cell apoptosis in mice treated with renal ischemia/reperfusion injury.Moreover,this protective effect could be reversed by AMPK inhibitors.These findings verify that human umbilical cord mesenchymal stem cell-derived exosomes exerting a protective effect on renal ischemia/reperfusion injury may be related to the activation of the AMPK/YAP1 pathway to antiapoptosis.

Objective To explore the effects and mechanisms of human umbilical cord mesenchymal stem cell (HUC-MSC)-derived exosomes (Exo) pretreated with Huangkui capsules on renal ischemia-reperfusion injury (IRI). Methods HUC-MSCs were cultured in media containing different concentrations of Huangkui capsules for 24 hours to determine cell viability and select an appropriate concentration for subsequent experiments. HUC-MSCs were pretreated with 50 μg/mL Huangkui capsules for 24 hours, and Exo were extracted using an exosome extraction kit. The morphology was observed under a transmission electron microscope, particle size was measured by nanoparticle tracking analysis, and the expression of exosomal membrane surface marker proteins was detected by Western blot. Human renal tubular epithelial cells (HK-2 cells) were randomly divided into hypoxia/reoxygenation group (M group), hypoxia/reoxygenation + Exo group (E group), and hypoxia/reoxygenation + Huangkui capsules pretreated Exo group (H group). Western blotting was used to measure the expression of endoplasmic reticulum stress (ERS)-related proteins, and real-time fluorescent quantitative reverse transcription polymerase chain reaction was used to measure the expression of ERS-related gene messenger RNA (mRNA). Mice were randomly divided into sham operation group (Sham group), ischemia-reperfusion group (I/R group), ischemia-reperfusion + Exo group (E group), and ischemia-reperfusion + Huangkui capsules pretreated Exo group (H group). Renal histological assessment, serum creatinine (Scr), blood urea nitrogen (BUN) measurement and inflammatory factor detection were performed 24 hours later. Results Both Exo and Huangkui capsules prereated Exo had a bilayer membrane structure and a cup-shaped morphology; their average particle sizes were 116.8 nm and 81.3 nm, respectively. Both expressed CD9, CD63, TSG101. Compared with the M group, the E group had decreased relative expression of transcription factor 6 (ATF6) and protein kinase R-like endoplasmic reticulum kinase (PERK) proteins, increased mRNA relative expression, increased relative expression of C/EBP homologous protein (CHOP) protein, and decreased mRNA relative expression. Compared with the E group, the H group had decreased relative expression of ATF6, PERK, CHOP proteins, and decreased mRNA relative expression of ATF6 and PERK (all P<0.05). Animal experimental results showed that compared with the Sham group, the I/R group had increased renal tubular injury scores, Scr, BUN, interleukin (IL)-1β, IL-10, IL-18, tumor necrosis factor (TNF)-α levels. Compared with the I/R group, the E and H groups had decreased renal tubular injury scores and Scr, BUN, IL-1β, IL-10, IL-18, TNF-α levels. Compared with the E group, the H group had decreased renal tubular injury scores and Scr, BUN, IL-1β, IL-10, IL-18, TNF-α levels (all P<0.05). Conclusions Huangkui capsules pretreatment HUC-MSC-derived Exo may alleviate renal IRI by inhibiting ERS.

Objective To explore the differences in scapular motion and shoulder function between patients suffering from rotator cuff tears(RCT)with and without type Ⅲ scapular dyskinesis(SD).Meth-ods Between September 2021 and March 2023,sixteen patients suffering from rotator cuff tears with SD(SD group)and 17 counterparts without SD(non-SD group)were recruited from the Sports Hospital of the General Administration of Sport of China.Their scapular motion was assessed by measuring three parameters in the X-rays,including scapular spine line(LSS),scapular upward rotation angle(SU-RA),and coracoid upward shift distance(CUSD).Moreover,their shoulder range of motion in flexion,abduction and external rotation were recorded,and further evaluated using the Pain Visual Analog Scale(VAS)and American Shoulder and Elbow Surgeons Score(ASES).Results No significant differenc-es were found between the two groups in the average score of SURA,CUSD and LSS at 0°～30° shoul-der abduction,or in that of CUSD and LSS at 60°～90°shoulder abduction.However,the average SU-RA score of the SD group at 60°～90°shoulder abduction was significantly greater than the other group(P<0.05).The shoulder ranges of motion during active flexion,abduction and external rotation were significantly smaller in the SD group than in the non-SD group(P<0.05).Moreover,the average VAS score in the SD group was significantly higher than the non-SD group(P<0.05),while the average ASES score was significantly lower than the latter group(P<0.05).Conclusions RCT patients type III SD exhibits greater scapular upward rotation during shoulder abduction compared to those without SD.Moreover,the former patients suffer from more severe pain and have worse shoulder range of motion and functional performance than the latter.

Pulmonary fibrosis is a respiratory system disorder characterized by damage to alveolar epithelial cells,pathological proliferation and transformation of fibroblasts,excessive deposition of extracellular matrix,leading to structural damage and loss of function in lung tissues,with a high mortality rate and limited effective treatment methods.This article was based on the TCM understanding of"lung connecting to large intestine",namely the theory of"lung and the large intestine being interior-exterior related",and set the modern medical understanding of"lung connecting to large intestine",namely the theory of"gut-lung axis"as the key.Combining the TCM pathogenesis of pulmonary fibrosis and the related mechanisms of"gut-lung axis"in pulmonary fibrosis,it preliminarily expounded the connotation of TCM regulating the"gut-lung axis"to treat pulmonary fibrosis,aiming to provide new ideas for clinical treatment of pulmonary fibrosis through the"gut-lung axis".

Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxidase-1 (HO-1) in reduction of renal ischemia-reperfusion (I/R) injury by the human umbilical cord mesenchymal stem cells (hucMSCs)-derived exosomes (hucMSCs-exo) in mice.Methods:The hucMSCs were cultured, and exosomes were extracted and identified by transmission electron microscopy, nanoparticle tracking analysis and Western blot. Thirty-six male SPF-grade C57BL/6 mice, weighing 20-25 g, were used. Thirty mice were selected and divided into 5 groups ( n=6 each) by a random number table method: sham operation group (Sham group), sham operation + Nrf2 inhibitor ML385 group (Sham + ML385 group), renal I/R group (I/R group), renal I/R + exosome group (I/R+ EXO group), and renal I/R + exosome + Nrf2 inhibitor ML385 group (I/R+ EXO+ ML385 group). A model of renal I/R injury was prepared by clamping the bilateral renal pedicles for 45 min followed by perfusion in anesthetized animals. ML385 30 mg/kg was intraperitoneally injected at 45 min before preparing the model in Sham+ ML385 group and I/R+ EXO+ ML385 group, and hucMSCs-exo 100 μg was injected via the tail vein at 15 min before reperfusion in I/R+ EXO group and I/R+ EXO+ ML385 group. Serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations were detected at 24 h of reperfusion. The renal tissues were obtained for examination of the pathological changes and for determination of contents of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA), superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels and expression of Nrf2 and HO-1 protein and mRNA (by Western blot and quantitative real-time polymerase chain reaction). The left 6 mice were allocated to sham operation group (Sham-IM group, n=3) and renal I/R group (I/R-IM group, n=3) by a random number table method for VISQUE in living imaging observation. Results:The exosomes showed a typical cup-shaped morphology with a transmission electron microscope, the nanoparticles tracked and analyzed the average diameter of the exosome, with an average diameter of 96.7 nm, and the positive expression of surface markers CD9, CD63 and TSG101 was detected using Western blot. The renal fluorescence intensity value was significantly increased in I/R-IM group as compared with Sham-IM group ( P<0.05). Compared with Sham group, the serum BUN and Cr concentrations were significantly increased, the contents of IL-6, TNF-α and MDA and ROS levels were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 protein and mRNA was down-regulated ( P<0.05), and the pathological changes of renal tissues were aggravated in I/R group, and no significant change was found in serum BUN and Cr concentrations in Sham+ ML385 group ( P>0.05). Compared with I/R group, the serum BUN and Cr concentrations were significantly decreased, the contents of IL-6, TNF-α and MDA and ROS levels were decreased, the activity of SOD was increased, the expression of Nrf2 and HO-1 protein and mRNA was up-regulated ( P<0.05), and the pathological changes of renal tissues were significantly attenuated in I/R+ EXO group. Compared with I/R+ EXO group, the serum BUN and Cr concentrations were significantly increased, the contents of IL-6, TNF-α and MDA and ROS levels were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 protein and mRNA was down-regulated ( P<0.05), and the pathological changes of renal tissues were aggravated in I/R+ EXO+ ML385 group. Conclusions:The mechanism by which hucMSCs-exo reduces renal I/R injury may be related to activation of the Nrf2/HO-1 signaling pathway in mice.