AIM:To evaluate the value of ultra-sound-guided erector spinae plane block(ESPB)combined with opioid-sparing anaesthesia in extra-corporeal shock wave lithotripsy(ESWL)for pancre-atic stones.METHODS:A total of 96 patients(60 males and 36 females,aged 20-65 years,ASA Ⅰ-Ⅱ,BMI 16-30 kg/m2)undergoing elective extracorpo-real shock wave lithotripsy for pancreatic duct stones were selected in our hospital from March 2022 to April 2023.The patients were randomly di-vided into conventional intravenous anesthesia group(group C,48 cases)and ESPB+opioid-sparing group(group E,48 cases).Patients in group C un-derwent general anesthesia with target-controlled infusion of propofol and remifentanil with sponta-neous breathing.Patients in group E underwent ul-trasound-guided bilateral ESPB before intravenous general anesthesia.The changes of hemodynamic indexes(HR,MAP)in the two groups were ob-served and recorded.The anesthetic effect,dosage of remifentanil,quality of anesthesia recovery,postoperative analgesic effect and incidence of perioperative adverse reactions(respiratory depres-sion,nausea and vomiting,pruritus,etc.)were ob-served in the two groups.RESULTS:Compared with group C,the incidence of intraoperative respiratory depression was significantly decreased,the intraop-erative consumption of remifentanil was de-creased,and the postoperative recovery time was shortened in group E(P＜0.05).The VAS scores of rest and cough pain and the incidence of postoper-ative nausea and vomiting were significantly de-creased in group E(P＜0.05).There was no signifi-cant difference in HR and MAP between the two groups(P＞0.05).CONCLUSION:Ultrasound-guided ESPB in ESWL for pancreatic duct stones is satisfac-tory and can save opioids with few complications.

AIM:To evaluate the value of ultra-sound-guided erector spinae plane block(ESPB)combined with opioid-sparing anaesthesia in extra-corporeal shock wave lithotripsy(ESWL)for pancre-atic stones.METHODS:A total of 96 patients(60 males and 36 females,aged 20-65 years,ASA Ⅰ-Ⅱ,BMI 16-30 kg/m2)undergoing elective extracorpo-real shock wave lithotripsy for pancreatic duct stones were selected in our hospital from March 2022 to April 2023.The patients were randomly di-vided into conventional intravenous anesthesia group(group C,48 cases)and ESPB+opioid-sparing group(group E,48 cases).Patients in group C un-derwent general anesthesia with target-controlled infusion of propofol and remifentanil with sponta-neous breathing.Patients in group E underwent ul-trasound-guided bilateral ESPB before intravenous general anesthesia.The changes of hemodynamic indexes(HR,MAP)in the two groups were ob-served and recorded.The anesthetic effect,dosage of remifentanil,quality of anesthesia recovery,postoperative analgesic effect and incidence of perioperative adverse reactions(respiratory depres-sion,nausea and vomiting,pruritus,etc.)were ob-served in the two groups.RESULTS:Compared with group C,the incidence of intraoperative respiratory depression was significantly decreased,the intraop-erative consumption of remifentanil was de-creased,and the postoperative recovery time was shortened in group E(P＜0.05).The VAS scores of rest and cough pain and the incidence of postoper-ative nausea and vomiting were significantly de-creased in group E(P＜0.05).There was no signifi-cant difference in HR and MAP between the two groups(P＞0.05).CONCLUSION:Ultrasound-guided ESPB in ESWL for pancreatic duct stones is satisfac-tory and can save opioids with few complications.

OBJECTIVE To investigate the effects of sacubitril/valsartan on renal function in patients with primary hypertension. METHODS A retrospective study was conducted among patients with primary hypertension who were admitted to PLA Strategic Support Force Characteristic Medical Center from January 2018 to June 2023. Based on their medication， they were divided into two groups： sacubitril/valsartan group and valsartan group. Propensity score matching was used to match baseline data between the two groups. Patients were treated with antihypertensive drugs based on improving their lifestyle. Sacubitril/valsartan group additionally received oral administration of 200 mg Sacubitril/valsartan tablets once daily， while valsartan group additionally received oral administration of 80 mg Valsartan capsules once daily. The increase amplitude of serum creatinine from baseline， the proportion of patients with elevated serum creatinine ＞30%-50% or ＞50%， and the proportion of patients with hyperkalemia （serum potassium ≥5.5 mmol/L） were compared between two groups at 2 months and 6 months after treatment. The trends of changes in serum creatinine， serum potassium and estimated glomerular filtration rate （eGFR） were compared between the two groups before treatment （at baseline）， 2 months and 6 months after treatment. RESULTS After propensity score matching， there were 62 patients in sacubitril/valsartan group and 61 patients in valsartan group； there were no significant differences in baseline characteristics between the two groups before treatment （P＞0.05）， indicating comparability. After 6 months of treatment， the increase of serum creatinine in the sacubitril/valsartan group was significantly lower than that in the valsartan group （P＝0.003）； the proportion of patients with elevated serum creatinine ＞30%-50% in the sacubitril/valsartan group was significantly lower than that in the valsartan group （P＝0.045）. None of the patients experienced hyperkalemia events after 2 months and 6 months of treatment. Repeated measures analysis of variance showed significantly statistical differences in serum creatinine and eGFR between the two groups within 6 months of treatment （P＜0.001）. Patients taking valsartan experienced a continuous increase in serum creatinine levels and a decrease in eGFR， while patients taking sacubitril/valsartan showed a first increase and then a decrease in serum creatinine levels， and a first decrease and then an increase in eGFR with a prolonged duration of medication. CONCLUSIONS Sacubitril/valsartan can delay or even reverse the decline in renal function levels， and limit the deterioration of renal function in patients with primary hypertension， without increasing the risk of hyperkalemia.

Objective:To investigate the effects of gelatin methacrylate anhydride (GelMA) hydrogel loaded with small extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUCMSCs-sEVs) in the treatment of full-thickness skin defect wounds in mice.Methods:This study was an experimental study. hUCMSCs-sEVs were extracted by ultracentrifugation, their morphology was observed through transmission electron microscope, and the expression of CD9, CD63, tumor susceptibility gene 101 (TSG101), and calnexin was detected by Western blotting. The human umbilical vein endothelial cells (HUVECs), the 3 rd and 4 th passages of human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs) were all divided into blank control group (routinely cultured) and hUCMSC-sEV group (cultured with the cell supernatant containing hUCMSCs-sEVs). The cell scratch test was performed and the cell migration rates at 6, 12, and 24 h after scratching were calculated, the cell Transwell assay was performed and the number of migration cells at 12 h after culture was calculated, and the proportion of proliferating cells was detected by 5-acetylidene-2'-deoxyuridine and Hoechst staining at 24 h after culture, with sample numbers being all 3. The simple GelMA hydrogel and the GelMA hydrogel loaded with hUCMSCs-sEVs (hereinafter referred to as hUCMSC-sEV/GelMA hydrogel) were prepared. Then the micromorphology of 2 kinds of hydrogels was observed under scanning electron microscope, the distribution of hUCMSCs-sEVs was observed by laser scanning confocal microscope, and the cumulative release rates of hUCMSCs-sEVs at 0 (immediately), 2, 4, 6, 8, 10, and 12 d after soaking hUCMSC-sEV/GelMA hydrogel in phosphate buffer solution (PBS) were measured and calculated by protein colorimetric quantification ( n=3). Twenty-four 6-week-old male C57BL/6J mice were divided into PBS group, hUCMSC-sEV alone group, GelMA hydrogel alone group, and hUCMSC-sEV/GelMA hydrogel group according to the random number table, with 6 mice in each group, and after the full-thickness skin defect wounds on the back of mice in each group were produced, the wounds were performed with PBS injection, hUCMSC-sEV suspenson injection, simple GelMA coverage, and hUCMSC-sEV/GelMA hydrogel coverage, respectively. Wound healing was observed on post injury day (PID) 0 (immediately), 4, 8, and 12, and the wound healing rates on PID 4, 8, and 12 were calculated, and the wound tissue was collected on PID 12 for hematoxylin-eosin staining to observe the structure of new tissue, with sample numbers being both 6. Results:The extracted hUCMSCs-sEVs showed a cup-shaped structure and expressed CD9, CD63, and TSG101, but barely expressed calnexin. At 6, 12, and 24 h after scratching, the migration rates of HEKs (with t values of 25.94, 20.98, and 20.04, respectively), HDFs (with t values of 3.18, 5.68, and 4.28, respectively), and HUVECs (with t values of 4.32, 19.33, and 4.00, respectively) in hUCMSC-sEV group were significantly higher than those in blank control group ( P<0.05). At 12 h after culture, the numbers of migrated HEKs, HDFs, and HUVECs in hUCMSC-sEV group were 550 ±23, 235 ±9, and 856 ±35, respectively, which were significantly higher than 188 ±14, 97 ±6, and 370 ±32 in blank control group (with t values of 22.95, 23.13, and 17.84, respectively , P<0.05). At 24 h after culture, the proportions of proliferating cells of HEKs, HDFs, and HUVECs in hUCMSC-sEV group were significantly higher than those in blank control group (with t values of 22.00, 13.82, and 32.32, respectively, P<0.05). The inside of simple GelMA hydrogel showed a loose and porous sponge-like structure, and hUCMSCs-sEVs was not observed in it. The hUCMSC-sEV/GelMA hydrogel had the same sponge-like structure, and hUCMSCs-sEVs were uniformly distributed in clumps. The cumulative release rate curve of hUCMSCs-sEVs from hUCMSC-sEV/GelMA hydrogel tended to plateau at 2 d after soaking, and the cumulative release rate of hUCMSCs-sEVs was (59.2±1.8)% at 12 d after soaking. From PID 0 to 12, the wound areas of mice in the 4 groups gradually decreased. On PID 4, 8, and 12, the wound healing rates of mice in hUCMSC-sEV/GelMA hydrogel group were significantly higher than those in the other 3 groups ( P<0.05); the wound healing rates of mice in GelMA hydrogel alone group and hUCMSC-sEV alone group were significantly higher than those in PBS group ( P<0.05). On PID 8 and 12, the wound healing rates of mice in hUCMSC-sEV alone group were significantly higher than those in GelMA hydrogel alone group ( P<0.05). On PID 12, the wounds of mice in hUCMSC-sEV/GelMA hydrogel group showed the best wound epithelization, loose and orderly arrangement of dermal collagen, and the least number of inflammatory cells, while the dense arrangement of dermal collagen and varying degrees of inflammatory cell infiltration were observed in the wounds of mice in the other 3 groups. Conclusions:hUCMSCs-sEVs can promote the migration and proliferation of HEKs, HDFs, and HUVECs which are related to skin wound healing, and slowly release in GelMA hydrogel. The hUCMSC-sEV/GelMA hydrogel as a wound dressing can significantly improve the healing speed of full-thickness skin defect wounds in mice.

A 61-year-old male patient with coronary heart disease was treated with dual antiplatelet therapy, lipid-lowering therapy (atorvastatin) and other symptomatic drugs after coronary interventions. Because the patient was at ultra-high-risk of cardiovascular events, had multiple in-stent restenosis, and had uncontrolled blood lipids, subcutaneous injection of evolocumab 140 mg was added once every 2 weeks. The platelet count (PLT) of the patient was within the reference range before evolocumab application. After 2 injections of evolocumab, he developed bloody sputum, blood blisters on the lips and scattered bleeding points around the body, with PLT 19×10 9/L. The dual antiplatelet therapy and evolocumab were suspended, but the bleeding was aggravated. According to the results of bone marrow puncture and biopsy, the patient was diagnosed with idiopathic thrombocytopenic purpura. Glucocorticoid, human immunoglobulin, recombinant human thrombopoietin and platelet transfusion were given but not effective. Subsequently, herombopag was added and PLT gradually increased. After 25 days, the PLT was 109×10 9/L.

A 61-year-old male patient with coronary heart disease was treated with dual antiplatelet therapy, lipid-lowering therapy (atorvastatin) and other symptomatic drugs after coronary interventions. Because the patient was at ultra-high-risk of cardiovascular events, had multiple in-stent restenosis, and had uncontrolled blood lipids, subcutaneous injection of evolocumab 140 mg was added once every 2 weeks. The platelet count (PLT) of the patient was within the reference range before evolocumab application. After 2 injections of evolocumab, he developed bloody sputum, blood blisters on the lips and scattered bleeding points around the body, with PLT 19×10 9/L. The dual antiplatelet therapy and evolocumab were suspended, but the bleeding was aggravated. According to the results of bone marrow puncture and biopsy, the patient was diagnosed with idiopathic thrombocytopenic purpura. Glucocorticoid, human immunoglobulin, recombinant human thrombopoietin and platelet transfusion were given but not effective. Subsequently, herombopag was added and PLT gradually increased. After 25 days, the PLT was 109×10 9/L.

【Objective】  To predict the active components and action targets of Wuyao (Linderae Radix) in the treatment of chronic pelvic inflammatory disease (CPID) based on network pharmacology, explore possible mechanisms of the treatment through animal experiments, and provide a scientific basis for clinical applications of Wuyao (Linderae Radix). 【Methods】  Possible active components and targets of Wuyao (Linderae Radix) in the treatment of CPID were obtained applying network pharmacology and molecular docking technology. CPID rat models were established using the mixed Escherichia coli, Staphylococcus aureus, and Ureaplasma urealyticum plus the performance of mechanical injury. Hematoxylineosin (HE) staining was applied to observe the pathological changes in the uterus, fallopian tube, and spleens of rat models. The contents of nitric oxide (NO), superoxide dismutase (SOD), and malondialdehyde (MDA) in the serum of rats were determined with the use of corresponding detection kits. Enzyme-linked immunosorbent assay (ELISA) test was used to measure the expression of interleukin (IL)-6 and IL-10 in the serum of rat models. Flow cytometry was used to determine the percentage of CD4+ and CD8a+ T cells as well as CD4+ CD25+ regulatory T cells (Tregs) in the spleen of rat models. 【Results】  A total of nine potential active components and four core therapeutic targets related to inflammatory response in Wuyao (Linderae Radix) were obtained. The animal experiments showed that Wuyao (Linderae Radix) markedly inhibited uterus swelling, regulated morphological changes in the fallopian tube and spleen,  effectively reduced inflammatory infiltration and injuries in the uterus and fallopian tube, and improved spleen functions in CPID rats. Moreover, Wuyao (Linderae Radix) markedly reduced the levels of NO, IL-6, and MDA, and increased the levels of IL-10 and SOD in the serum of rats. Wuyao (Linderae Radix) also elevated the percentage of CD4+T cells and the CD4+ T/CD8a+ T cell ratio, reduced the percentage of CD8a+ T cells, and raised the percentage of CD4+ CD25+ Tregs that had been abnormally decreased in rat models (P < 0.05). 【Conclusion】  Wuyao (Linderae Radix) could have therapeutic effects on CPID rats by relieving oxidative stress, mitigating inflammatory levels, and regulating the immuno-function of T cell subgroups to improve the pathological changes in CPID rats. It is a medicinal herb worth being further explored for its clinical values.

ERα-36 is a novel subtype of estrogen receptor α which promotes tumor cell proliferation, invasion and drug resistance, and it serves as a therapeutic target. However, only small-molecule compounds targeting ERα-36 are under development as anticancer drugs at present. Gene therapy approach targeting ERα-36 can be explored using recombinant adenovirus armed with decoy receptor. The recombinant shuttle plasmid pDC316-Ig κ-ERα-36-Fc-GFP was constructed via genetic engineering to express an Ig κ-signaling peptide-leading secretory recombinant fusion protein ERα-36-Fc. The recombinant adenovirus Ad-ERα-36-Fc-GFP was subsequently packaged, characterized and amplified using AdMax^TM adenovirus packaging system. The expression of fusion protein and functional outcome of Ad-ERα-36-Fc-GFP transduction were further analyzed with triple-negative breast cancer MDA-MB-231 cells. Results showed that the recombinant adenovirus Ad-ERα-36-Fc-GFP was successfully generated. The virus effectively infected MDA-MB-231 cells which resulted in expression and secretion of the recombinant fusion protein ERα-36-Fc, leading to significant inhibition of EGFR/ERK signaling pathway. Preparation of the recombinant adenovirus Ad-ERα-36-Fc-GFP provides a basis for further investigation on cancer gene therapy targeting ERα-36.
Adenoviridae/genetics* ; Cell Proliferation ; Estrogen Receptor alpha/metabolism* ; Recombinant Proteins ; Transfection

Objective:To compare the treatment outcomes of neoadjoint therapy combined with liver transplantation versus radical hepatectomy for patients with surgically resectable hilar cholangiocarcinoma.Methods:A retrospective study was performed on the data of 64 patients with resectable hilar cholangiocarcinoma operated from January 2009 to December 2014 at the Organ Transplantation Department of the First Central Hospital of Tianjin. There were 43 males and 21 females, with an average age of 61.2 years. There were 45 patients who underwent radical hepatectomy in the liver resection group, and 19 patients who underwent combined neoadjuvant therapy (radiotherapy combined with 5-fluorouracil intravenous drip, transcatheter lumen radiotherapy, capecitabine oral administration) and liver transplantation in the liver transplantation group. The recurrence rates and survival rate were compared between groups.Results:The 1, 3 and 5 years cumulative survival rates of the liver transplantation group were 89.5%, 73.7% and 63.2%, respectively, which were significantly better than those of the liver resection group (80.0%, 53.3% and 35.6%) ( P<0.05). The postoperative tumor recurrence rate in the liver transplantation group was 31.6% (6/19), which was significantly lower than that in the liver resection group of 60.0% (27/45) ( P<0.05). Subgroup analysis using postoperative pathological results showed the cumulative survival rates of patients without lymph node metastasis (N 0) and those with negative resection margins (R 0) were not significantly different between groups ( P>0.05). However, for patients with regional lymph node invasion (N 1) and with R 0 resection margin, the cumulative survival rates at 1, 3 and 5 years after liver transplantation were 83.3%, 66.7% and 50.0%, respectively, which were significantly superior to the 64.3%, 28.6% and 14.3% of the liver resection group ( P<0.05). Conclusion:Hepatectomy is recommended for patients with N 0 R 0 resectable hilar cholangiocarcinoma. For patients with hilar cholangiocarcinoma with marginally resectable N 1R 0, neoadjuvant therapy combined with liver transplantation resulted in significantly better long-term overall survival than resection.

Objective To compare the difference of clinical efficacy between surgical magnifying glass and surgical microscope assisted hepatic artery reconstruction in living donor liver transplantation (LDLT). Methods Clinical data of 272 donors and recipients undergoing LDLT were retrospectively analyzed. According to different patterns of hepatic artery reconstruction, all recipients were divided into the magnifying glass group (n=189) and microscope group (n=83). The operation time, intraoperative blood loss, hepatic artery reconstruction site, diameter of anastomosis, incidence of postoperative complications and survival rate of recipients were statistically compared between two groups. Results Compared with the microscope group, the operation time, hepatic artery reconstruction time and intraoperative blood loss were significantly less in the magnifying glass group (all P < 0.001). The most common site of hepatic artery reconstruction was the right hepatic artery in two groups, and the diameter of anastomosis was (2.1±0.9) mm in the magnifying glass group and (2.1±0.8) mm in the microscope group, with no statistical significance between two groups (P > 0.05). The 1-, 2- and 3-year survival rates of recipients in the magnifying glass group were 88%, 86% and 85%, which did not significantly differ from 89%, 87% and 86% in the microscope group (all P > 0.05). The incidence of postoperative complications did not significantly differ between two groups (all P > 0.05). Conclusions The efficacy and safety of hepatic artery reconstruction in LDLT under surgical magnifying glass are equivalent to those under surgical microscope, with less operation workload and intraoperative blood loss. For experienced transplantation surgeons, it is recommended to perform hepatic artery reconstruction assisted by surgical magnifying glass.