ObjectiveTo explore the potential mechanism of Dingchuan Granule （定喘颗粒， DG） in the treatment of respiratory syncytial virus （RSV） pneumonia. MethodsA total of 60 male Sprague Dawley （SD） rats were randomly divided into control group， model group， ribavirin group， DG low-dose group， DG middle-dose group， and DG high-dose group， with 10 rats in each group. Except for the control group， rats were administrated with RSV via intranasal drip. After model establishment， the DG low-， middle-， and high-dose groups were administrated via oral gavage with DG at 3.47， 6.93， and 13.86 g/（kg·d） respectively， while the ribavirin group was administrated via oral gavage with ribavirin at 15.75 mg/（kg·d）. The drug was given once daily for one week. The rats in the control group and the model group were not given any drug， only subjected to the grasping action. Twenty-four hours after the last administration， the pathological changes of lung tissues were observed and scored using HE staining. The levels of serum inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）， were detected by colorimetry. The protein levels of nuclear factor （erythroid derived 2）-like 2 （Nrf2）， Kelch-like ECH-associated protein 1 （Keap1）， heme oxygenase 1 （HO-1）， and NAD（P）H quinone dehydrogenase 1 （NQO1） in lung tissues were measured by Western Blot. The RSV load as well as the gene expression levels of Nrf2， Keap1， HO-1， and NQO1 in lung tissues were determined by qRT-PCR. The level of reactive oxygen species （ROS） in rat lung tissues was detected using chemiluminescence. The levels of glutathione （GSH） and malondialdehyde （MDA） in rat lung tissues were measured by a microassay. ResultsCompared with the control group， other groups had significant increases in pathological score of lung tissue， RSV load， levels of ROS， MDA， serum TNF-α， IL-1β， and IL-6； decrease in GSH level， increases in expression level of Keap1 protein and its mRNA in lung tissue， and significant decrease in levels of Nrf2， HO-1， expression level of NQO1 protein and its mRNA （P＜0.05）. Compared with the model group， all the above-mentioned indicators in the DG low-， middle-， and high-dose groups and the ribavirin group were improved to varying degree （P＜0.05）. The levels of serum TNF-α， IL-1β， and IL-6 in rats of DG dose groups showed a dose-dependent pattern， the DG high-dose group exhibiting the best effect （P＜0.05）. The DG high-dose group was superior to the DG low- and middle-dose groups in reducing the levels of ROS and MDA， and increasing the level of GSH in lung tissues （P＜0.05）. The DG high-dose group and the ribavirin group had better effect than the DG middle-dose group in reducing the RSV load （P＜0.05）. The DG high-dose group was superior to the ribavirin group in improving the protein levels of Nrf2， Keap1， HO-1， and NQO1 （P＜0.05）. ConclusionDG could inhibit oxidative stress by regulating the Nrf2/Keap1/HO-1/NQO1 signaling pathway to improve pulmonary inflammation and treat RSV pneumonia， with the DG high-dose group showing the best effect.

Integrin α _v β ₃ is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of ¹⁷⁷Lu-AB-3PRGD2, a novel integrin α _v β ₃-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α _v β ₃-avid tumors were recruited to accept ¹⁷⁷Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. ¹⁷⁷Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of ¹⁷⁷Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α _v β ₃-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.

OBJECTIVE: To observe the effects of enhanced rehabilitation on the prognosis of critically ill patients in the intensive care unit (ICU). METHODS: A single-center retrospective historical controlled study was conducted, patients admitted to the ICU of Peking University First Hospital from May 1, 2020, to April 30, 2021, and from October 1, 2021, to September 30, 2022 were enrolled. According to the different rehabilitation treatment strategies during different periods, patients were divided into the conventional rehabilitation group (patients receiving conventional rehabilitation treatment from May 1, 2020, to April 30, 2021) and the enhanced rehabilitation group (patients receiving the therapy of multidisciplinary team, ie medical care-rehabilitation-nursing care from October 1, 2021, to September 30, 2022). General data, acute physiology and chronic health evaluation II (APACHE II), and study endpoints were collected. Primary endpoints included rehabilitation-therapy rate, intervention time for rehabilitation, rehabilitation-related adverse events, and prognostic indicators such as (length of stay in hospital, length of stay in the ICU, and duration of mechanical ventilation). Secondary endpoints included incidence of deep vein thrombosis and hospital mortality. Kaplan-Meier curves were used to analyze cumulative discharge rates within 50 days. RESULTS: A total of 539 ICU patients were enrolled, with 245 in the conventional rehabilitation group and 294 in the enhanced rehabilitation group; 322 patients had an APACHE II score ≤ 15, while 217 patients had an APACHE II score > 15. Compared to the conventional rehabilitation group, the enhanced rehabilitation group demonstrated significantly higher rehabilitation-therapy rate [51.70% (152/294) vs. 11.43% (28/245)], earlier intervention time for rehabilitation [days: 2.00 (1.00, 3.00) vs. 4.00 (3.00, 7.00)]; shorter length of stay in hospital [days: 18.00 (12.00, 30.00) vs. 21.00 (13.00, 36.00)] and lower incidence of DVT [17.01% (50/294) vs. 24.08% (59/245)]. The differences were all statistically significant (all P < 0.05). There were no rehabilitation-related adverse events occurred in either group. Kaplan-Meier analysis demonstrated a significantly higher cumulative discharge rate within 50 days in the enhanced rehabilitation group compared to the conventional rehabilitation group [86.7% (255/294) vs. 82.9% (203/245); Log-Rank test: χ² = 4.262, P = 0.039]. Subgroup analysis showed that for patients with APACHE II score ≤ 15, the enhanced rehabilitation subgroup had higher rehabilitation-therapy rate [44.32% (78/176) vs. 6.16% (9/146), P < 0.05]. For patients with APACHE II score > 15, compared to the conventional rehabilitation group, the enhanced subgroup demonstrated higher rehabilitation-therapy rate [62.71% (74/118) vs. 19.19% (19/99), P < 0.05] and shorter length of stay in hospital [days: 20.50 (12.00, 31.25) vs. 26.00 (16.00, 43.00), P < 0.05]. CONCLUSIONS Enhanced rehabilitation therapy with medical care, rehabilitation and nursing care, improved rehabilitation-therapy rate, advanced time of rehabilitation treatment, reduced length of stay in hospital and incidence of deep vein thrombosis in critically ill patients, particularly benefited those with APACHE II score > 15. The enhanced rehabilitation was beneficial to the patient in the intensive care unit with safety and worth more investigation.
Humans ; Retrospective Studies ; Critical Illness/rehabilitation* ; Intensive Care Units ; Prognosis ; Length of Stay ; APACHE ; Historically Controlled Study ; Male ; Female ; Middle Aged ; Aged

This article presents a case study of a patient who had Cronkhite-Canada syndrome in combination with an asymptomatic novel coronavirus infection. The patient exhibited clinical symptoms of loss of appetite, hair and nail loss, and skin pigmentation. Digestive endoscopy revealed widespread and varying-sized polypoid changes in the mucosa of the stomach, duodenum, and colon. During the course of the illness, the patient tested positive for novel coronavirus nucleic acid. Treatment with moderate doses of prednisone resulted in the patient's hair regrowth and decreased skin hypopigmentation. The article provides a summary of the patient's diagnosis and treatment and a review of relevant literature, with the aim of enhancing clinicians' understanding of the disease.

Objective:To analyze the characteristics of postoperative thoracic deformation in patients who underwent multi-rib autologous rib cartilage transplantation auricle reconstruction based on 3dMD imaging system.Methods:A retrospective study was conducted using 3dMD data of the thorax from patients who underwent auricle reconstruction surgery using multiple autologous costal cartilages at the First Department of Ear Reconstruction of the Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from July to September 2019. The normal-side chest wall image was superimposed on the rib-harvested side chest wall for automatic registration and alignment, with distance numerical data presented in a Cartesian heat map through color mapping technology. By observing the areas where the rib-harvested side thorax had obvious deformation, the distance difference of the concave and convex peaks on the sagittal diameter was measured to judge the degree of thoracic deformation in children (≤10 mm as none; >10-20 mm as mild; >20-30 mm as moderate; >30 mm as severe).Results:A total of 42 children were included, with 27 males and 15 females, aged from 7 to 12 years old. The Cartesian heat map of thoracic deformation showed that the obvious concave area of the chest wall was located at the junction of the middle and inner one-third of the clavicle and the 7th rib, and the obvious convex area was located in the area from the nipple to the 5th rib. The measurement range of the protrusion peak in the upper chest nipple area was from -7.638 9 to -14.288 4 mm; the measurement range of the depression peak in the rib arch area was from 7.238 7 to 14.653 2 mm. The range of the distance difference between the concave and convex peaks was from 14.877 6 to 28.941 6 mm.The degree and incidence of thoracic deformation in children: mild in 5 cases; moderate in 37 cases.Conclusion:Based on the analysis with 3dMD photogrammetry, the overall characteristics of chest wall deformation in patients who underwent ear reconstruction with autologous rib cartilage grafts were the coexistence of protrusion in the upper chest nipple area and depression in the area where the rib cartilage was harvested, with changes occurring on the sagittal diameter.

Objective:To analyze the characteristics of postoperative thoracic deformation in patients who underwent multi-rib autologous rib cartilage transplantation auricle reconstruction based on 3dMD imaging system.Methods:A retrospective study was conducted using 3dMD data of the thorax from patients who underwent auricle reconstruction surgery using multiple autologous costal cartilages at the First Department of Ear Reconstruction of the Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from July to September 2019. The normal-side chest wall image was superimposed on the rib-harvested side chest wall for automatic registration and alignment, with distance numerical data presented in a Cartesian heat map through color mapping technology. By observing the areas where the rib-harvested side thorax had obvious deformation, the distance difference of the concave and convex peaks on the sagittal diameter was measured to judge the degree of thoracic deformation in children (≤10 mm as none; >10-20 mm as mild; >20-30 mm as moderate; >30 mm as severe).Results:A total of 42 children were included, with 27 males and 15 females, aged from 7 to 12 years old. The Cartesian heat map of thoracic deformation showed that the obvious concave area of the chest wall was located at the junction of the middle and inner one-third of the clavicle and the 7th rib, and the obvious convex area was located in the area from the nipple to the 5th rib. The measurement range of the protrusion peak in the upper chest nipple area was from -7.638 9 to -14.288 4 mm; the measurement range of the depression peak in the rib arch area was from 7.238 7 to 14.653 2 mm. The range of the distance difference between the concave and convex peaks was from 14.877 6 to 28.941 6 mm.The degree and incidence of thoracic deformation in children: mild in 5 cases; moderate in 37 cases.Conclusion:Based on the analysis with 3dMD photogrammetry, the overall characteristics of chest wall deformation in patients who underwent ear reconstruction with autologous rib cartilage grafts were the coexistence of protrusion in the upper chest nipple area and depression in the area where the rib cartilage was harvested, with changes occurring on the sagittal diameter.

Objective To observe the expression of GLIS3 in triple negative breast cancer(TNBC)and analyze its relationship with the prognosis of TNBC patients.Methods Bioinformatic analysis was applied to analyze the expression level of GLIS3 in Gene Expression Omnibus(GEO).Kaplan-Meier survival curve was plotted to evaluate the impact of GLIS3 expression on the survival rate of patients based on DNA chip data.A total of 125 patients pathologically diagnosed as TNBC in the Fourth Hospital of Hebei Medical University from January to December 2014 were enrolled by cluster random sampling.Among them,53 patients had complete tissue specimens,medical records and follow-up data.Immunohistochemical assay was used to detect the expression of GLIS3 in TNBC and adjacent tissues to tumors,while the relationships between GLIS3 protein expression in breast cancer tissues and clinicopathological parameters such as age,menstrual status,tumor size,clinical stage,histological grade,pathological type,axillary lymph node metastasis,vascular tumor thrombus,and expression of TP53 and Ki-67 were analyzed.Kaplan-Meier survival curve was plotted to analyze the effect of GLIS3 on the overall and disease-free survival of TNBC patients.Cox regression model was established to identify the risk factors impacting the prognosis of the patients.Results Analysis of GEO data showed that the expression of GLIS3 in TNBC was significantly higher than that in paracancer tissues(P＜0.05).The expression of GLIS3 was notably higher in the TNBC tissue than the adjacent tissue to tumor(P＜0.05).A marked augmentation of GLIS3 expression was observed in both the advanced and larger-sized tumors(P＜0.05).Univariate analysis of Cox regression model revealed that lymph node metastasis,TNM stage and GLIS3 expression were all related to disease-free survival of TNBC patients(P＜0.05).Univariate and multivariate analyses displayed that TNM stage was related to the overall survival of TNBC patients(P＜0.05).The patients with high expression of GLIS3 had significant shorter disease-free survival time than those with low expression(P＜0.05),but had no statistical difference in overall survival(P＞0.05).Conclusion GLIS3 protein is highly expressed in TNBC tissues,and tumor size and TNM stage are correlated with its high expression.The high expression of GLIS3 suggests that the patients have poor prognosis and low disease-free survival rate.

Objective:To investigate the effect of perineal single-port robot-assisted radical prostatectomy.Methods:A retrospective analysis was conducted on clinical data from 60 patients who underwent perineal single-port robot-assisted laparoscopic radical prostatectomy at our hospital between July 2019 and July 2022. The mean age of the patients was (65.9±7.6) years and the mean BMI was (24.1±2.9) kg/m 2. The median (IQR) prostate volume was 32.7 (23.8, 41.2) ml, and the median (IQR) preoperative PSA value was 8.8 (6.8, 12.6) ng/ml. Preoperative pathology revealed a Gleason score of 6 in 21 patients, Gleason score of 7 in 35 patients and Gleason score of 8 in 4 patients. There were 12 patients clinically staged as T 1 and 48 patients as T 2. A total of 18 patients underwent a total of 23 previous abdominopelvic surgeries. The patient is placed in an exaggerated lithotomy position with the head down and feet elevated approximately 15°. A 3-5 cm incision was made approximately 2 cm above on the mid-perineum between the bilateral ischial tuberosities. Next, the rectourethral muscle was divided, and the space anterior to the rectum was developed by blunt dissection. The levator ani muscles were separated to expose Denonvilliers’ fascia. Then, the disposable multi-channel laparoscopic surgical access system is inserted with a surgical wound protector. Denonvilliers’ fascia was incised transversely and the ampulla of the vas deferens, which were subsequently divided. Blunt separation is performed on both sides along the capsule of the prostate, and then, the vascular pedicles of the prostate are ligated. The membranous urethra was severed after complete urethral separation at the tip of the prostate at the urethral junction. The bladder neck was freed and dissected. The prostate and seminal vesicles were removed and a vesicourethral anastomosis is performed. A perineal drain were left in place. Preoperative and postoperative variables, complications, early urinary continence rate(Return of urinary continence status was defined as using no more than one safety pad per day) and oncological outcomes of patients were recorded. Results:All 60 surgeries were successfully completed without conversions or additional incisions. The median (IQR) total operative time was 200.0(153.8, 236.3) min, the median (IQR) console operating time was 107.5(90.0, 150.0) min and the median (IQR) estimated blood loss was 50.0(50.0, 100.0) ml. Positive surgical margins were detected in five patients (8.3%). The continence rate was 43.1%(22/51), 64.7%(33/51), 92.0%(46/50) and 98.0%(49/50), and the PSA undetectable rate was 94.6%(48/51), 98.2%(49/51), 96.6%(47/50) and 100%(50/50) at the 1, 3, 6, and 12 months after surgery. Only 1(1.7%) patient experienced biochemical recurrence 9 months after surgery. The overall complication rate was 20%, including two cases of acute respiratory distress syndrome, one case of rectal injury, one case of urinary tract injury, two cases of poor wound healing, three cases of incision infection, two cases of urinary tract infection and one case of bladder neck-urethral orifice anastomotic stricture.Conclusions:Perineal single-port robot-assisted radical prostatectomy might be safe and feasible surgical treatments for localized prostate cancer, especially for patients with a history of complex abdominal or pelvic surgery. It also showed advantages in early continence. The anatomical structure of the perineal region should be considered, and the correct incision position should be chosen. Specific incision protection measures should also be used for the incision in this particular area of the perineal region to reduce the risk of perioperative complications.

A 31-year-old man sought medical evaluation for a 2-year history of edema and proteinuria, with prior pathology suggesting atypical membranous nephropathy (MN). Despite treatment with a combination of steroids, calcineurin inhibitors, and four courses of rituximab (1 g, intravenous injection), the patient′s nephrotic syndrome showed no relief (24 h urine protein peaked at 31.18 g/d), indicating refractory nephrotic syndrome. Later in the disease course, a sudden surge of creatinine level (322.5 μmol/L) prompted a renal biopsy, which revealed concurrent acute interstitial nephritis. Further treatment involving steroids, cyclophosphamide, and a fifth rituximab infusion (1 g, intravenous injection) resulted in improvement in renal function (serum creatinine: 322.5?147 μmol/L), but the MN failed to achieve partial relief. Subsequent treatment with the novel humanized CD20 monoclonal antibody obinutuzumab (1 g, intravenous injection) was initiated. In the latest follow-up, anti-phospholipase-A2-receptor antibody (PLA2R) antibody were negative, B cells were eliminated, serum albumin was 36 g/L, urine protein-to-creatinine ratio was 4 810 mg/g, and serum creatinine was 162 μmol/L. This case underscores the potential efficacy of obinutuzumab in refractory MN. For advanced MN cases, prompt identification of the cause of acute kidney injury is crucial, emphasizing the need for targeted interventions to potentially stall renal function decline.

Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair.Among the elements that lead to DDP resistance,O6-methylguanine(O6-MG)-DNA-meth-yltransferase(MGMT),a DNA-repair enzyme,performs a quintessential role.In this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo.Conversely,in cancer cells,MGMT overexpression abolishes their sensi-tivity to DDP treatment.Mechanistically,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1.Meanwhile,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy drugs.Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant cells.In summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.