ObjectiveTo investigate the mechanisms by which Bushen Tongluo Jiangzhuo prescription improves renal fibrosis in rats with chronic kidney disease （CKD） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsSeventy specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a control group （n=15） and a modeling group （n=55）. Rats in the modeling group were administered a 2.5% adenine suspension at a dose of 200 mg·kg^-1·d^-1 by gavage for 4 weeks to establish a CKD model. Successfully modeled rats were randomly divided into a model group， an irbesartan group （20.25 mg·kg^-1·d^-1）， and Bushen Tongluo Jiangzhuo prescription low-， medium-， and high-dose groups （5.82， 11.64， and 23.28 g·kg^-1·d^-1， respectively）， with 10 rats in each group. Each group was administered an equal volume of physiological saline， the corresponding concentration of irbesartan， or Bushen Tongluo Jiangzhuo prescription by gavage for 12 weeks. Body weight and renal function indices were dynamically monitored. Serum creatinine （SCr）， blood urea nitrogen （BUN）， urine albumin-to-creatinine ratio （ACR）， 24-hour urinary total protein （24 hUTP）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） levels were measured using an automatic biochemical analyzer. Renal histopathological changes were observed by hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry （IHC） was used to detect the expression of PI3K， Akt， phosphorylated Akt （p-Akt）， and mTOR in renal tissues. Western blot was performed to assess the protein expression of PI3K， p-Akt， Akt， phosphorylated mTOR （p-mTOR）， and mTOR in renal tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression levels of PI3K， Akt， and mTOR in renal tissues. ResultsCompared with the model group， rats in the irbesartan group and the low-， medium-， and high-dose Bushen Tongluo Jiangzhuo prescription groups showed significantly decreased levels of SCr， BUN， ACR， 24 hUTP， IL-1β， IL-6， and TNF-α （P<0.01）. AST levels were significantly increased （P<0.01）， while no significant difference was observed in ALT levels. Histopathological examination revealed that， compared with the model group， renal tubular epithelial cell edema and necrosis and Bowman's capsule dilation were alleviated， inflammatory cell infiltration was reduced， and interstitial and glomerular fibrosis was markedly improved in all treatment groups， with the most pronounced effect observed in the high-dose Bushen Tongluo Jiangzhuo prescription group. Real-time PCR results showed that mRNA expression levels of PI3K， Akt， and mTOR were significantly downregulated in the high-dose group （P<0.01）. IHC results demonstrated that PI3K and p-Akt expression levels in renal tissues were significantly decreased in the high-dose group （P<0.01）. Western blot analysis further confirmed that the expression levels of PI3K， p-Akt/Akt， and p-mTOR/mTOR were significantly reduced in the high-dose group （P<0.01）. ConclusionBushen Tongluo Jiangzhuo prescription improves renal function indices in CKD rats， reduces collagen deposition in renal tissues， and decreases serum inflammatory factor levels. Its protective effect on renal function may be achieved by activating autophagy through downregulation of the PI3K/Akt/mTOR signaling pathway， thereby alleviating renal fibrosis.

ObjectiveTo investigate the molecular mechanism by which the Bushen Kaixuan Tongluo prescription exerts a renal protective effect in mice with diabetic kidney disease （DKD） by regulating the cyclic adenosine monophosphate （cAMP） signaling pathway. MethodsThirty specific pathogen-free （SPF） male db/db mice were adaptively fed for three weeks. Mice with a random tail vein blood glucose level ≥ 11.1 mmol·L^-1 and urinary albumin-creatinine ratio （ACR） ≥ 30 mg·g^-1 were considered successfully modeled. The successfully modeled mice were randomly divided into five groups with six mice in each group： the model group， the low-， medium-， and high-dose Bushen Kaixuan Tongluo prescription groups （administered at doses of 7， 14， 28 g·kg^-1·d^-1 respectively）， and the positive drug irbesartan group （administered at a dose of 20 mg·kg^-1·d^-1）. Additionally， six db/m mice were selected as the blank group. Mice in each group were given intragastric administration of the Bushen Kaixuan Tongluo prescription at the corresponding concentrations， irbesartan， or an equal volume of pure water， and the intervention lasted for 12 weeks. During the experiment， the general conditions， body weight changes， and renal function indicators of the mice were dynamically monitored. After the intervention， a blood glucose meter was used to measure the fasting blood glucose （FBG） of the mice. An automatic biochemical analyzer was employed to detect the levels of serum creatinine （SCr）， blood urea nitrogen （BUN）， urinary microalbumin （uALB）， ACR， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglycerides （TG）， leptin （LEP）， glycosylated serum protein （GSP）， and insulin （INS） in the mice. Renal tissues were collected for hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson's trichrome staining to observe the histopathological changes. Immunohistochemistry （IHC） was used to detect the expressions of protein kinase A （PKA） and cAMP response element-binding protein （CREB） in the mice. Western blot analysis was performed to determine the expression levels of PKA， phosphorylated protein kinase A （p-PKA）， CREB， phosphorylated cAMP response element-binding protein （p-CREB）， and B-cell lymphoma-2 （Bcl-2） proteins in the renal tissues of the mice. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of PKA， CREB， and Bcl-2 in the renal tissues of the mice. ResultsCompared with the blank group， the mice in the model group showed listlessness， decreased activity， and a significant increase in body weight （P<0.01）. Biochemical indicators revealed that the levels of BUN， uALB， ACR， AST， ALT， TC， TG， FBG， LEP， GSP， and INS were significantly increased （P<0.01）， while SCr showed an increasing trend with no statistically significant difference. Compared with the model group， the mice in the Bushen Kaixuan Tongluo prescription intervention groups had improved general conditions and a decreasing trend in body weight. Biochemical indicators showed that the levels of BUN， uALB， ACR， TC， GSP， and INS were significantly decreased （P<0.05）， while SCr， AST， ALT， TG， and LEP showed a decreasing trend with no statistically significant difference. Renal histopathological analysis showed that the model group exhibited typical DKD pathological features such as thickening of the glomerular basement membrane， expansion of the mesangial matrix， and deposition of collagen fibers in the renal tubulointerstitium， and all treatment groups could alleviate the above pathological damages. The IHC results showed that compared with the blank group， the expression levels of p-PKA and p-CREB in the renal tissues of the model group were significantly decreased （P<0.01）. Compared with the model group， the expression level of p-PKA in the medium-dose Bushen Kaixuan Tongluo prescription group was significantly increased （P<0.01）， while the expression level of p-CREB showed an increasing trend with no statistically significant difference. Western blot results showed that compared with the blank group， the expression levels of p-PKA/PKA， p-CREB/CREB， and Bcl-2 in the model group were significantly decreased （P<0.05）. Compared with the model group， the expression levels of these proteins in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly increased （P<0.01）. Real-time PCR results showed that compared with the blank group， the mRNA expressions of PKA， CREB， and Bcl-2 in the model group were significantly down-regulated （P<0.05）. Compared with the model group， the mRNA expressions of these genes in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly up-regulated （P<0.05）. ConclusionThe Bushen Kaixuan Tongluo prescription can improve the liver and kidney functions of db/db mice， correct lipid metabolism disorders and glucose metabolism imbalance. Its renal protective effect is associated with up-regulating the cAMP signaling pathway to improve renal fibrosis and reduce the level of oxidative stress， thereby protecting renal function.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

This study investigated the regulatory potential of salidroside (SAL), a primary active compound in Rhodiola rosea L., on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha (HIF-1a) pathway in osteoblasts. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to validate whether the receptor activator of nuclear factor-?B ligand (RANKL) is the downstream target gene of HIF-1a in osteoblasts. The study also utilized lipopolysaccharide (LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo. Furthermore, conditioned medium (CM) from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1a pathway. Hypoxic condition-induced overexpression of HIF-1a upregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells. In vivo, SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1a by downregulating the expression of RANKL, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and angiopoietin-like 4 (ANGPTL4). In the paracrine experiment, conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. RANKL emerges as the downstream target gene regulated by HIF-1a in osteoblasts. SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
Animals ; Osteoblasts/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Glucosides/administration & dosage* ; Cell Differentiation/drug effects* ; Phenols/administration & dosage* ; Mice ; Osteoclasts/metabolism* ; RANK Ligand/genetics* ; Rhodiola/chemistry* ; Osteogenesis/drug effects* ; Signal Transduction/drug effects* ; Interleukin-6/genetics* ; Male ; RAW 264.7 Cells ; Osteolysis/genetics* ; Humans ; Mice, Inbred C57BL

ObjectiveTo investigate the expression of serum Aldo-keto reductase family 1 member B10 （AKR1B10） in patients with hepatocellular carcinoma （HCC） in northern China， and to provide a new and valuable biomarker for the clinical diagnosis of HCC. MethodsThis study was conducted among 102 patients with HCC， 119 patients with benign liver disease， and 132 patients with other malignant tumors who attended The Affiliated Hospital of Chengde Medical University and 148 healthy individuals who underwent physical examination from May 2020 to May 2024. ELISA and chemiluminescence were used to measure the serum levels of AKR1B10 and alpha-fetoprotein （AFP）. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between three groups and further comparison between two groups； the chi-square test was used for comparison of categorical data between groups. The area under the ROC curve （AUC） was used to assess diagnostic efficiency. ResultsThe expression level of AKR1B10 was 3 053.79 （1 475.67‍ ‍—‍ ‍4 605.86） pg/mL in the HCC group， 1 324.42 （659.68‍ ‍—‍ ‍2 023.88） pg/mL in the benign liver disease group， 660.68 （377.56‍ ‍—‍ ‍2 087.77） pg/mL in the other malignant tumor group， and 318.30 （82.73‍ ‍—‍ ‍478.82） pg/mL in the healthy group， with a significant difference between the four groups （H=240.86， P<0.001）， and further comparison between two groups showed that the HCC group had a significantly higher level than the other three groups （all P<0.001）. The ROC curve analysis of the HCC group and the other three groups showed that serum AKR1B10 had an optimal cut-off value of 1 584.97 pg/mL in the diagnosis of HCC， with an AUC of 0.86 （95% confidence interval ［CI］： 0.82‍ ‍—‍ ‍0.90）， a sensitivity of 74.3%， and a specificity of 85.2%. Compared with each indicator alone， a combination of AKR1B10 and AFP could improve the sensitivity （81.8%） and specificity （91.4%） of HCC diagnosis. AKR1B10 had an AUC of 0.84 （95%CI： 0.78‍ ‍—‍ ‍0.90） in the diagnosis of patients with early- or middle-stage HCC， with a sensitivity of 76.2% and a specificity of 81.2%. AKR1B10 had an AUC of 0.85 （95%CI： 0.77‍ ‍—‍ ‍0.92） in the diagnosis of patients with AFP-negative HCC， with a sensitivity of 81.6% and a specificity of 79.9%. ConclusionAKR1B10 is a promising serological marker for the diagnosis of HCC， and a combination of AKR1B10 and AFP can improve the detection rate of HCC patients in northern China， especially those with early- or middle-stage HCC and AFP-negative HCC.

Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

[Purpose]To analyze the survival rate of prostate cancer patients hospitalized in Nan-tong Tumor Hospital from 2007 to 2017.[Methods]A total of 478 prostate cancer patients were admitted in Nantong Tumor Hospital from 2007 to 2017 and 476 cases(99.58％)were followed up till December 31,2020.The survival rate of patients was analyzed with Kaplan-Meier method;Soft-ware SPSS 25.0 and the Log-rank test were employed for statistical analysis.[Results]The aver-age age of prostate cancer patients at admission was(71.74±8.02)years old,and 79.08％were aged 60～79 years.The median survival time was 43 months,and the observed 1-,3-,5-and 10-year survival rates were 77.20％,56.07％,43.01％and 24.53％,respectively.The 5-year survival rates for the age groups of 35～59,60～79 and ≥80 years old were 31.73％,46.64％and 29.65％,respectively(P＜0.05).The 5-year survival rates for patients with stage Ⅰ～Ⅱ,stage Ⅲ,stage IV,and unknown stage were 88.10％,71.66％,33.35％and 37.55％,respectively(P＜0.001).The 5-year survival rates for the periods 2007-2012 and 2013-2017 were 32.85％and 47.79％,re-spectively(P＜0.05).Furthermore survival rates differed significantly across different regions within the jurisdiction(P＜0.05).[Conclusion]Over the past decade,the survival rate of hospital-based prostate cancer patients has significantly improved.Early-stage cases can achieve better survival rates,but the survival rate of elderly patients remains a challenge.Efforts should be made to reduce the proportion of patients with unknown staging Comprehensive measures for prostate cancer prevention and control should be strengthened to reduce incidence,improve prognosis and enhance quality of life of patients.

Objective:To investigate the correlation between expressions of serum procalcitonin (PCT), T-cell immunogloblin domain, mucin domain 4 (TIM-4) and prognosis of patients with severe pneumonia (SP) treated with bronchoalveolar lavage (BAL).Methods:Data of 497 patients with SP in the Department of Respiratory and Critical Care Medicine of the Affiliated Hospital of Yan'an University from June 2021 to June 2024 were retrospectively analyzed. Patients were divided into good prognosis group [pneumonia severity index (PSI) score<90 points, 289 cases] and poor prognosis group (PSI score≥90 points, 208 cases) according to the prognosis status of patients at 30 days after admission. The clinical data [history of smoking, alcohol consumption, history of hypertension, history of diabetes mellitus, gender, age, body mass index, PSI score after 30 d of admission, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and clinical pulmonary infection score (CPIS) after 14 days of treatment], serum PCT and TIM-4 levels were compared between both groups. Measurement data with normal distribution were expressed as xˉ± s, and t test was used for comparison between groups. Enumeration data were represented as n (%), and the composition ratio between groups was compared by χ2 test. The influencing factors of prognosis of BAL in the treatment of SP were analyzed by multivariate Logistic regression analysis. ROC curve was applied to analyze the diagnostic efficiency of serum PCT and TIM-4 on prognosis of BAL therapy. Results:Age (56.79±11.98) years, APACHEⅡscore (9.98±3.27) and CPIS score (6.54±1.81) in the good prognosis group were younger or lower than those in the poor prognosis group [(62.74±10.57) years, (13.06±4.25), (8.12±1.97)] ( t=5.734, 9.127, 9.250, respectively, P<0.001). The PCT (0.41±0.08) μg/L and TIM-4 (61.79±15.62) ng/L after treatment were higher in the poor prognosis group than those in the good prognosis group [(0.35±0.07) μg/L, (48.76±14.58) ng/L] ( t=8.876, 9.538, respectively, P<0.001). Multivariate Logistic regression analysis suggested that after excluding the interference effects of other factors, PCT ( OR=3.615, 95% CI: 1.641-7.964) and TIM-4 ( OR=4.047, 95% CI: 1.773-9.236) were influencing factors of prognosis in patients with SP receiving BAL therapy ( P=0.002, 0.001). ROC curve analysis indicated that the AUC value of PCT, TIM-4 and the combination of both in the diagnosis of prognosis of BAL therapy of SP were 0.782, 0.828 and 0.887 respectively, all of which had efficiency on predicting prognosis (all P<0.001). The sensitivity and specificity of combined prediction were 88.00% and 72.00%. Conclusion:The expressions of serum PCT and TIM-4 are closely related to the prognosis of SP patients receiving BAL. The PCT, TIM-4 and combination of both are of important reference value for prognosis prediction.

Objective:To investigate the effects of red laser versus plasma transurethral enucleation of the prostate (TUEP) on urinary and sexual function in patients under 65 years of age with benign prostatic hyperplasia (BPH).Method:This study was a retrospective analysis. Eighty BPH patients under 65 years old, admitted to the Affiliated Hospital of Yan'an University between January 2020 and January 2023 were selected. Among them, 40 patients who underwent 980 nm semiconductor red laser TUERP with pre-resection of the urethral mucosa 1 cm proximal to the verumontanum at the prostatic apex and preservation of bladder neck integrity were assigned to the Red Laser Group. Another 40 patients who underwent conventional TURP with a plasma resectoscope were assigned to the Plasma Group. Clinical data and 6-month postoperative follow-up data were collected. Changes in the International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax), International Index of Erectile Function-5 (IIEF-5) score, ejaculatory function score, and ejaculatory discomfort score before and after surgery were compared between the two groups. The incidence rates of decreased semen volume, retrograde ejaculation, and painful ejaculation at 6 months postoperatively were also compared.Results:At 6 months postoperatively, IPSS decreased in both groups compared to preoperative levels and was lower in the Red Laser Group than in the Plasma Group [(4.7±1.3) points vs. (6.3±2.2) points, t=-4.46, P<0.001]. Qmax increased in both groups compared to preoperative levels and was higher in the Red Laser Group than in the Plasma Group [(25.7±1.3) ml/s vs. (22.6±1.2) ml/s, t=10.76, P<0.001]. The ejaculatory function score in the Plasma Group was lower than its own preoperative level [(5.9±0.7) points vs. (11.1±1.6) points, t=5.33, P<0.001] and lower than that in the Red Laser Group [(5.9±0.7) points vs. (11.4±0.9) points, t=7.56, P<0.001]. The ejaculatory discomfort score in the Plasma Group was higher than its own preoperative level [(3.0±1.5) points vs. (0.8±0.6) points, t=4.26, P<0.001] and higher than that in the Red Laser Group [(3.0±1.5) points vs. (0.8±0.6) points, t=5.83, P<0.001]. The incidence rates of decreased semen volume and retrograde ejaculation in the Red Laser Group were lower than those in the Plasma Group [12.5% (5/40) vs. 50.0% (20/40), 10.0% (4/40) vs. 45.0% (18/40), χ2=15.84, 12.65, respectively, both P<0.001]. Conclusions:Using 980 nm semiconductor red laser TUERP with pre-resection of the urethral mucosa 1 cm proximal to the verumontanum and preservation of bladder neck integrity can improve urinary and sexual function in BPH patients under 65 years of age.

OBJECTIVE T o explore the prevention and control measures for the hospital-acquired pulmonary mu-cormycosis caused by Cunninghamella bertholletiae.METHODS One case of patient with pulmonary mucormyco-sis caused by Cunninghamella bertholletiae who was treated in pediatric intensive care unit(PICU)of a three-A general hospital was enrolled in the study,the process of clinical diagnosis and treatment was summarized.A ret-rospective survey regarding four aspects including people,machine,materials and environment was conducted.The related factors leading to the hospital-acquired infections in the patient were analyzed.RESULTS The child was diagnosed with severe aplastic anemia and underwent hematopoietic stem cell transplantation,the child was treated with various invasive procedures during the treatment period and was infected with pulmona-ry mucormycosis caused by the rare Cunninghamella bertholletiae.The occurrence of the pulmonary mucormyco-sis was associated with the poor management of medical textile,insufficient environmental cleaning and disinfec-tion and nonstandard invasive procedures.CONCLUSIONS The Cunninghamella bertholletiae infection is less com-mon,but the risk of death is high.It is necessary for the medical institutions to complete the prevention and con-trol measures and intensify the health care workers'capabilities in identification of the pathogenic fungus so as to reduce the incidence of pulmonary mucormycosis caused by the pathogen.