OBJECTIVE To study the safety of Shuangshu decoction in rats and its efficacy in improving functional dyspepsia （FD） in rats. METHODS In safety test， 40 rats were divided into blank control group， Shuangshu decoction low-dose， medium- dose and high-dose groups [108， 216， 324 g/（kg·d）， calculated by raw medicine， the same applies below]； they were given relevant medicine intragastrically， for continuous 14 days. The mortality and toxic reactions of rats were recorded， and the organ indexes of the liver， kidney， spleen， lung and heart of rats were calculated； the pathological morphological changes in the liver， kidney， spleen， lung， heart， stomach， duodenum， and colon were observed to evaluate the acute toxicity of Shuangshu decoction. Another 40 rats were grouped and administered in the same way for 30 consecutive days. The mortality and toxic reactions of the rats were recorded， and the corresponding organ indexes were calculated. The pathological morphological changes in the corresponding organs were observed， and blood routine and serum biochemical indicators were measured， in order to assess the subacute toxicity of Shuangshu decoction. In pharmacodynamic experiments: 50 rats were divided into blank control group， model group， and Shuangshu decoction low-， medium-， and high-dose groups （9.45， 18.9， 37.8 g/kg）， with 10 rats in each group. Except for blank control group， rats in all other groups were used to establish the FD rat model by subcutaneous injection of loperamide （3.5 mg/kg）. Rats in each group were administered the corresponding drug solution/normal saline intragastrically， once a day， for 14 consecutive days. After the last medication， fecal moisture content， intestinal propulsion rate， gastric emptying rate and serum level of motilin were all detected， and interstitial cell of Cajal （ICC） ultrastructure of rats was observed in colon tissue. RESULTS The safety experiments showed that no death occurred in each dose group， and no significant difference was found in organ coefficient， routine blood and serum biological index， compared to blank control group （P＞0.05）； no abnormality was found in organ appearance and pathological sections. The results of the pharmacodynamic experiments showed that， compared with the blank control group， the fecal moisture content， gastric emptying rate， intestinal propulsion rate， and serum motilin levels in the model group were significantly decreased （P＜0.05）； in the colonic tissue， the mitochondria in the ICC exhibited severe swelling with the disappearance of cristae， and the endoplasmic reticulum was dilated. Compared with model group， the rats in Shuangshu decoction high-dose group showed significant increases in the above quantitative indicators （P＜ 0.05）； additionally， there was a large number of mitochondria in the ICC of the colonic tissue， with clear cristae and regular arrangement. CONCLUSIONS Shuangshu decoction is safe and has a beneficial improving effect on FD rats； its mechanism of action may be related to the regulation of gastrointestinal hormone expression to promote gastric emptying and intestinal propulsion， as well as the repair of mitochondrial structure in ICCs to restore gastrointestinal function.

Objective: To evaluate the effects of dietary intervention on blood pressure and renal function in patients with hypertensive nephropathy, so as to provide dietary and nutritional guidances for this population. Methods: Hypertensive nephropathy patients who were treated at Zhucheng People's Hospital from March 2023 to February 2024 were selected as the study subjects and randomly divided into the intervention group and the control group. The control group received routine antihypertensive treatment and health lifestyle guidance. On the basis of the treatment and guidance received by the control group, the intervention group implemented dietary intervention in accordance with the Clinical Practice Guidelines for Nutritional Therapy of Chronic Kidney Disease in China (2021 edition) for a period of 3 months. Systolic blood pressure (SBP), diastolic blood pressure (DBP) were measured before and after the intervention, and serum creatinine (Scr), blood urea nitrogen (BUN), uric acid (UA), cystatin and β2-microglobulin were detected. Differences of indicators before and after intervention between the two groups were compared using generalized estimation equation. Results: A total of 83 patients with hypertensive nephropathy were followed up, including 43 cases in the intervention group and 40 cases in the control group. There were no statistically significant differences in gender, age, body mass index, duration of hypertension, family history of hypertension, hypertension grade, physical activity index, or smoking status between the two groups (all P>0.05). The differences in SBP, DBP, Scr, BUN, and UA between the two groups, as well as the differences before and after the intervention, were statistically significant, and there was an interaction between the groups and the intervention time (all P<0.05). After intervention, the levels of SBP, DBP, Scr, BUN, and UA in the intervention group were lower than those in the control group (all P<0.05). The differences in cystatin and β2-microglobulin between the two groups and before and after the intervention were not statistically significant, and there was no interaction between the groups and the intervention time (all P>0.05). Conclusion Dietary intervention has a certain effect on reducing blood pressure and improving renal function indicators in patients with hypertensive nephropathy.

OBJECTIVE To investigate the inhibitory effect and mechanism of Modified qifang weitong granules on gastric cancer based on in vitro and in vivo experiments. METHODS Human gastric cancer HGC-27 cells were divided into the following groups: control group （treated with fetal bovine serum）， 10% drug-containing serum group， 15% drug-containing serum group， 20% drug-containing serum group， and 5-fluorouracil （5-Fu） group （positive control， 3.90 μg/mL）. After culturing the cells in each group with the corresponding serum/drug solution， their proliferation， migratory and invasive abilities， as well as the cell cycle， were assessed. Additionally， the expression levels of epithelial-mesenchymal transition （EMT）-related proteins [E-cadherin， N-cadherin， and vimentin] in the cells were measured. Logarithmic-phase HGC-27 cells were harvested and subcutaneously injected into the right axillary region of nude mice to establish a subcutaneous xenograft tumor model in nude mice. The successfully modeled tumor-bearing nude mice were randomly divided into model group， low-， medium- and high-dose groups of Modified qifang weitong granules （17.65， 35.29 and 70.58 g/kg， respectively）， and 5-Fu group （25 mg/kg）， with 5 mice in each group. After 14 days of treatment with the corresponding drugs in each group， the histopathological morphology of the tumor tissues in the nude mice was observed. Immunohistochemistry and Western blot assay were employed to detect the expression levels of EMT- related proteins in the tumor tissues of the nude mice. RESULTS In the cell experiment， compared with the control group， the cell proliferation rate， migration rate， number of invasive cells， as well as the expression levels of N-cadherin and vimentin proteins， and the percentage of cells in the G2/M phase were all significantly decreased/reduced in the 15% drug-containing serum group， 20% drug-containing serum group （P＜0.05）. Conversely， the percentage of cells in the G0/G1 phase and the expression level of E- cadherin protein were significantly increased （P＜0.05）. In animal experiment， compared with the model group， the high-dose group of Modified qifang weitong granules exhibited significantly reduced tumor mass and expression levels of N-cadherin and vimentin proteins in the tumor tissues of nude mice （P＜0.05）， while the expression level of E-cadherinprotein in the tumor tissues was significantly increased （P＜0.05）. Additionally， the tumor cells varied in size and showed extensive necrosis. CONCLUSIONS Modified qifang weitong granules effectively inhibit gastric cancer in both in vitro and in vivo models， and the mechanism of action is related to the suppression of EMT.

OBJECTIVE: To investigate the biological effect of medical recombinant human-derived collagen functional dressings in wound healing. METHODS: MTT assay and RTCA assay were used to detect cell toxicity and proliferation. Scratch assay and Transwell cell migration assay were used to detect cell motility and migration ability. Enzyme-linked immunosorbent assay was used to detect the contents of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-endothelial cell adhesion molecule (CD31) in the supernatant of four types of cells. After animal surgery, the surgical wound was taken at 1 week, 4 weeks and 13 weeks, respectively, for hematoxylin eosin (HE) staining and immunohistochemistry to observe the inflammatory response and CD31 expression of the wound. RESULTS: Medical recombinant human-derived collagen functional dressing promotes cell proliferation and migration, enhances wound angiogenesis by upregulating the expression of VEGF, FGF, and CD31 in human dermal vascular endothelial cells (HDVEC) and human vascular endothelial cells (HVEC), thereby improving local blood supply to the wound, regulating the inflammatory response of the wound, and accelerating wound healing. CONCLUSION Recombinant type Ⅲ humanized collagen plays an important role in wound healing.
Humans ; Wound Healing/drug effects* ; Recombinant Proteins/pharmacology* ; Animals ; Cell Proliferation ; Cell Movement ; Collagen/pharmacology* ; Vascular Endothelial Growth Factor A/metabolism* ; Bandages ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism* ; Endothelial Cells ; Fibroblast Growth Factors/metabolism*

OBJECTIVES: To explore the mechanism of Shuangshu Decoction (SSD) for inhibiting growth of gastric cancer xenografts in nude mice. METHODS: Network pharmacology analysis was conducted to identify the common targets of SSD and gastric cancer cell ferroptosis, and bioinformatics analysis and molecular docking were used to validate the core targets. In the cell experiment, AGS cells were treated with SSD-medicated serum, Fer-1 (a ferroptosis inhibitor), or both, and the changes in cell viability, ferroptosis markers (ROS, Fe²⁺ and GSH), expressions of P53, SLC7A11 and GPX4, and mitochondrial morphology were examined. In a nude mouse model bearing gastric cancer xenografts, the effects of gavage with SSD, intraperitoneal injection of Fer-1, or their combination on tumor volume/weight, histopathology, and expressions of P53, SLC7A11 and GPX4 levels were evaluated. RESULTS: The active components in SSD (quercetin and wogonin) showed strong binding affinities to P53. In AGS cells, SSD treatment dose-dependently inhibited cell proliferation, increased ROS and Fe²⁺ levels, upregulated P53 expression, and downregulated the expressions of SLC7A11 and GPX4, but these effects were effectively attenuated by Fer-1 treatment. SSD also induced mitochondrial shrinkage and increased the membrane density, which were alleviated by Fer-1. In the tumor-bearing mouse models, gavage with SSD significantly reduced tumor size and weight, caused tumor cell necrosis, upregulated P53 and downregulated SLC7A11 and GPX4 expression in the tumor tissue, and these effects were obviously mitigated by Fer-1 treatment. CONCLUSIONS SSD inhibits gastric cancer growth in nude mice by inducing cell ferroptosis via the P53/SLC7A11/GPX4 axis.
Ferroptosis/drug effects* ; Animals ; Stomach Neoplasms/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Mice, Nude ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Amino Acid Transport System y+/metabolism* ; Mice ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Xenograft Model Antitumor Assays

OBJECTIVE: To analyze the imaging and clinical features of diaphragm dysfunction in patients who underwent selective cardiac sternotomy with diaphragm ultrasound and chest CT. METHODS: A prospective cohort study was conducted. The patients undergoing selective cardiac sternotomy in the cardiac and vascular surgery department of Tianjin Medical University General Hospital from June to September 2023 were enrolled. Bedside ultrasound was performed on the day before surgery, within 24 hours of extubation, and on the 7th day after surgery to measure diaphragm excursion (DE) and diaphragm thickness (DT), and to calculate the diaphragm thickening fraction (DTF). The distance from the diaphragm's apex to the thorax's apex in the chest CT scout view was measured before and after the operation, and the diaphragm elevating fraction (DEF) was calculated. Patients were divided into two groups based on whether diaphragm dysfunction (DE < 1 cm) occurred on the 7th day after surgery. The change patterns of imaging indicators were analyzed in both groups. The clinical data of both groups before, during, and after surgery were compared. RESULTS: In total, 67 patients who underwent cardiac sternotomy were enrolled. Among them, 24 patients developed diaphragm dysfunction within 24 hours after extubation; on the 7th day after surgery, 19 patients (28.4%) still exhibited diaphragm dysfunction, while 48 patients (71.6%) did not. Ultrasonic examination of the diaphragm revealed that, compared with the non-diaphragm dysfunction group, patients in the diaphragm dysfunction group exhibited varying degrees of decrease in DE and DTF before and after surgery, with a more significant decrease on the left side, and the differences were statistically significant on the 7th day after surgery [DE (cm): 1.06±0.77 vs. 1.59±0.63, DTF: 19.3% (14.8%, 21.1%) vs. 21.3% (18.3%, 26.1%), both P < 0.05]. There was no statistically significant difference in DT between the two groups at each time point. Changes in bilateral DE and DTF revealed that the non-diaphragm dysfunction group experienced early transient postoperative weakening of diaphragm function, followed by rapid recovery to the preoperative level on the 7th day after surgery, unlike the diaphragm dysfunction group. There were no significant differences between bilateral DE in the two groups on the day before surgery, and the left DE was significantly lower than the right DE within 24 hours after extubation and on the 7th day after surgery in the diaphragm dysfunction group (cm: 0.93±0.72 vs. 1.45±0.70 within 24 hours after extubation, 1.06±0.77 vs. 1.70±0.92 on the 7th day after surgery, both P < 0.05) but no significant difference was found in bilateral DT or DTF. The chest CT scan showed that, the incidence of postoperative diaphragm elevation was 61.2% (41/67), and 38.8% (26/67) did not, while no statistically significant difference in DEF was found between the two groups, nor within each group on both sides. Analysis of the clinical data showed a higher proportion of atrial fibrillation and pulmonary hypertension before surgery [atrial fibrillation: 36.8% (7/19) vs. 10.4% (5/48), pulmonary hypertension: 15.8% (3/19) vs. 2.1% (1/48), both P < 0.05], a higher incidence of high-flow oxygenation and pneumonia during surgery [high-flow oxygenation: 52.6% (10/19) vs. 25.0% (12/48), pneumonia: 73.7% (14/19) vs. 45.8% (22/48), both P < 0.05], and a longer duration of mechanical ventilation and length of intensive care unit (ICU) stay [duration of mechanical ventilation (hours): 47.0 (38.0, 73.0) vs. 24.5 (20.0, 48.0), length of ICU stay (hours): 69.0 (65.0, 117.5) vs. 60.0 (42.3, 90.6), both P < 0.05] in the diaphragm dysfunction group as compared with those in the non-diaphragm dysfunction group. CONCLUSIONS There was a high incidence of diaphragm dysfunction after cardiac sternotomy, which reflected the early transient postoperative weakening of diaphragm function, followed by rapid recovery to the preoperative level in most patients, predominantly on the left side. Diaphragm dysfunction, which was associated with atrial fibrillation and pulmonary hypertension significantly increased the incidence of postoperative pneumonia and prolonged the duration of mechanical ventilation and length of ICU stay.
Humans ; Diaphragm/physiopathology* ; Prospective Studies ; Sternotomy/adverse effects* ; Ultrasonography ; Postoperative Complications/diagnostic imaging* ; Tomography, X-Ray Computed ; Male ; Female ; Middle Aged ; Aged ; Cardiac Surgical Procedures/adverse effects*

Objective:To explore the relationship between the hypertensive snowbirds′ length of migratory stay and their blood pressure control and blood pressure levels.Methods:This study was a cross-sectional study. A population of snowbirds with hypertension was recruited between October and November 2022, and a structured questionnaire was used to collect their self-measured blood pressure and length of stay in Hainan Province. The blood pressure control status is determined based on self-measured blood pressure. According to the self-measured blood pressure to determine whether the blood pressure was well controlled. The associations between snowbirds′ length of stay and their blood pressure control as well as their self-measured blood pressure were analyzed using restricted cubic splines.Results:A total of 362 research subjects were included, 169(46.7%) of whom were male, and their age was (69.7±7.0) years old. The participants′ self-measured systolic blood pressure and diastolic blood pressure were (129.1±16.2) mmHg (1 mmHg=0.133 kPa) and (78.9±10.1) mmHg, respectively. Overall, 174 (48.1%) participants attained adequate blood pressure control. The median length of stay in Wuzhishan City was 7(6, 7) months. There was an inverted U-shaped association between snowbirds′ length of stay and blood pressure control (overall: P=0.023; nonlinearity: P=0.014), where participants with a length of stay of 7 months had the highest rate of blood pressure control. There is a U-shaped curve relationship between length of stay and systolic blood pressure (overall: P=0.001; nonlinearity: P=0.033), and a linear negative correlation with diastolic blood pressure ( β=-1.19, P=0.003). Conclusions:Compared with hypertensive snowbirds with too long or too short lengths of stay, snowbirds who stayed in Wuzhishan City for seven months have better blood pressure control, and systolic blood pressure is also lower.

Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is un-known.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the acti-vation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphory-lation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by acti-vating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

Objective To compare the difference between four-axis positioning 3D printing guide assisted puncture and manual puncture percutaneous vertebroplasty,to clarify the clinical efficacy of 3D printing guide assisted percutaneous vertebroplasty,and to explore its clinical application value.Methods A total of 70 patients who underwent single-segment vertebroplasty for osteoporotic vertebral compression fractures in our hospital were randomly divided into a manual group(control group)and a guide plate group(observation group).Thirty-five patients in the control group underwent PVP under the traditional manual puncture,and 35 patients in the observa-tion group underwent PVP under the four-axis positioning 3D printing guide assisted puncture.The general data,perioperative data,imaging data,preoperative and postoperative functional scores of the two groups were collected and compared.Results In terms of intraoperative fluoroscopy times,operation time,and postoperative adverse reactions,the observation group was significantly lower than the control group,and the difference was statistically significant(P<0.05).However,there was no significant difference between the two groups in intraoperative blood loss,bone cement leakage,and whether bone cement perfusion included fracture sites.In terms of clinical efficacy,the ratio of anterior vertebral height,postoperative VAS score and postoperative JOA score of the two groups were significantly better than those before operation,and the difference was statistically significant(P<0.05).At the same time point before and after operation,there was no significant difference in the height ratio of the anterior edge of the injured vertebra,VAS score and JOA score between the two groups(P>0.05).Conclusion The clinical efficacy of four-axis positioning 3D printing guide plate-assisted puncture is the same as that of experienced clinicians with free hand puncture for PVP,which can quickly relieve pain and improve dysfunction.However,guide plate assistance can shorten the operation time,reduce the number of fluoroscopy and postoperative adverse reactions,and make vertebroplasty faster and safer.

Objective: To observe the preventive effect of alkaline drinking water on hyperuricemia in mice. Methods: Sixty male SPF Kunming mice were randomly divided into six groups: pH 7.3, pH 8.0, pH 9.3 intervention groups, in which the mice were given water with pH values of 7.3±0.5, 8.0±0.5 and 9.3±0.6, respectively; the control group, model group and positive drug group ( with 2 g/L allopurinol ) were given double distilled water. Except for the control group, the mice in each group were given yeast by gavage (1.5 g/mL) for 13 days. On the 14th day, the mice were injected with 300 mg/kg potassium oxyzinate by intraperitoneal injection, and then fasted for 1 day. On the 16th day, serum uric acid, creatinine and urea nitrogen were detected, and renal tissues were stained to observe the morphology.The expression levels of neutrophil gelatinase-associated lipocalin ( NGAL ), tissue inhibitor of metalloproteinase 1( TIMP1 ), organic anion transporter 1 ( OAT1 ) and urate transporter 1 ( URAL-1 ) in renal tissues were determined bywestern blotting. The mRNA expression levels of URAL-1 and OAT1 were detected by real-time fluorescent quantita⁃tive polymerase chain reaction. Results: The level of serum uric acid was higher in the model group than in the control group and in the pH 9.3 intervention group (both P<0.05). The number and area of renal tubular lesions were less in the pH 9.3 intervention group than in the model group (all P<0.05). The relative expression levels of NGAL and URAT-1 proteins were lower in the pH 9.3 intervention group than in the model group, and the relative expression level of OAT1 protein was higher in the pH 9.3 intervention group than in the model group ( all P<0.05). The relativeexpression level of URAT-1 mRNA was lower in the pH 9.3 intervention group than in the model group, and the rela⁃tive expression level of OAT1 mRNA was higher in the pH 9.3 intervention group than in the model group ( all P<0.05 ). Conclusion Alkaline drinking water with pH value of 9.3±0.6 can effectively prevent hyperuricemia and acute kidney injury in mice.