The crosstalk between macrophages and bone marrow mesen chymal stem cells （BMSCs） plays a vital role in regulating tendon-bone healing. Based on the traditional Chinese medicine （TCM） theory that the kidney governs the bones and generates marrow， yin-nourishing and kidney-tonifying Chinese medicines can promote the osteogenic differentiation of BMSCs and the M1-to-M2 polarization of macrophages， thereby facilitating tendon-bone healing. A variety of related medicinal monomers （such as diosgenin and oleanolic acid）， extracts and effective fractions （such as artificial tiger bone powder and total flavonoids of Drynaria fortunei ）， as well as compound prescriptions （such as Liuwei dihuang pill， Xujin jiegu decoction and Duhuo jisheng decoction）， can modulate the crosstalk between macrophages and BMSCs by regulating the Wnt/β-catenin， nuclear factor kappa-B， phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin and transforming growth factor-β/Smad signaling pathways. They further exert anti-inflammatory， antioxidant and osteogenic effects to effectively accelerate tendon-bone healing. However， current evidence was limited to animal experiments exhibiting such as limitations insufficent alignment between animal models and clinical injury types， research focusing mostly on single signaling pathways， and unclear core active ingredients. Future studies shall optimize animal models and carry out large-sample randomized controlled trials， clarify the interactive networks of multiple signaling pathways， and isolate the core active substances of yin-nourishing and kidney-tonifying Chinese medicines， so as to advance the precise application of traditional Chinese medicines.

ObjectiveTo investigate the potential mechanism of Liangxue Tuizi Formula （凉血退紫方， LXTZF） in treating Henoch-Schönlein Purpura （HSP） by examining its regulatory effect on neutrophil extracellular trap （NETs） dysregulation via the rapidly accelerated fibrosarcoma kinase （RAF）/mitogen-activated protein kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodsSeventy Wistar rats were randomly allocated into a blank control group （n=14） and a modeling group （n=56）. Rats in the modelling group underwent an eight-week modelling period to establish HSP rat models with blood-heat syndrome via modified ovalbumin （OVA） induction method combined with oral administration of heat-property Chinese herbal medicine. Fifty successfully modeled rats were subsequently randomly divided into five groups （n=10 per group）， model group， compound glycyrrhizin group， LXTZF group， RAF inhibitor group， and LXTZF + RAF agonist group. Additionally， 10 rats were selected from the original blank control group for the final experiment. From the 11th week of modelling， rats in the blank control group and the model group received 1 ml/（100 g·d） ultrapure water via oral administration， in addition to 0.5 ml/（kg·d） 0.9% sodium chloride solution via intraperitoneal injection. The LXTZF group and the compound glycyrrhizin group received 7.5 g/（kg·d） LXTZF granule suspension via gavage， 13.5 mg/（kg·d） compound glycyrrhizin suspension via gavage， respectively. The RAF inhibitor group received 1 mg/（kg·d） GW5074 suspension via intraperitoneal injection and ultrapure water via oral administration； the LXTZF + RAF agonist group received 7.5 g/（kg·d） LXTZF granule suspension via gavage and 1 mg/（kg·d） paclitaxel suspension via intraperitoneal injection. All administrations were performed once daily for 4 weeks. After intervention， skin tissue histopathology was examined by hematoxylin and eosin （H&E） staining， immunoglobulin A （IgA） deposition was assessed via immunofluorescence， serum levels of neutrophil elastase （NE）， tumor necrosis factor-α （TNF-α）， and vascular cell adhesion molecule-1 （VCAM-1） were measured using enzyme-linked immunosorbent assay （ELISA）， serum myeloperoxidase （MPO） level was determined by a colorimetric assay； the mRNA expression levels of RAF， MEK， and ERK in skin tissue were detected by real-time quantitative polymerase chain reaction （RT-qPCR）； and the protein expression of RAF， MEK， ERK， as well as phosphorylated MEK （p-MEK） and phosphorylated ERK （p-ERK）， were analyzed by Western Blot. ResultsSkin tissue in the blank control group rats remained normal， whereas the model group exhibited neutrophil infiltration and haemorrhage with red blood cell rupture. In all drug intervention groups， neutrophil infiltration and haemorrhagic exudation reduced markedly， with LXTZF group demonstrating the most pronounced improvement. Compared with the blank control group， rats in the model group exhibited enhanced IgA fluorescence intensity in skin tissue， elevated serum levels of NE， MPO， TNF-α and VCAM-1， increased mRNA expression of RAF， MEK， ERK1 and ERK2， as well as heightened RAF protein levels and p-MEK/MEK and p-ERK/ERK ratios （P＜0.05）. Compared with the model group， the drug intervention groups exhibited reduced IgA fluorescence intensity in skin tissue， along with decreased serum levels of NE， MPO， TNF-α， and VCAM-1 （P＜0.05）. In LXTZF group and RAF inhibition groups， reduced mRNA expression of RAF， MEK， ERK1， and ERK2 was observed in rat skin tissue， alongside decreased RAF protein levels and reduced p-MEK/MEK and p-ERK/ERK ratios （P＜0.05）. Compared with LXTZF + RAF agonist group， the compound glycyrrhizin group， LXTZF group， and RAF inhibitior group exhibited reduced IgA fluorescence intensity in skin tissue， decreased serum NE， MPO， TNF-α， and VCAM-1 levels， and decreased MEK mRNA expression and p-MEK/MEK ratio （P＜0.05）. ConclusionThe potential mechanism by which LXTZF treats Henoch-Schönlein purpura with blood heat syndrome may involve blocking the RAF/MEK/ERK signaling pathway in skin tissue， and suppressing excessive formation of NETs， thereby reducing IgA deposition in dermal microvessels and attenuating systemic inflammatory responses.

Objective The purpose of this study is to investigate the expression of histone lysine-specific demethylase 1 (KDM1A) and ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) in thyroid cancer (TC) tissue and its relationship with clinical features and prognosis. Methods 94 TC patients diagnosed and treated at the Third Hospital of Heilongjiang Province from January 2017 to January 2019 were retrospectively selected as the study subjects. Immunohistochemistry was used to detect the expression of KDM1A and UCHL3 in tissues. Spearman correlation analysis was used to investigate the correlation between KDM1A and UCHL3. Kaplan-Meier survival curve was used to analyze the relationship between the levels of KDM1A and UCHL3 and the 5-year progression-free survival rate of TC patients. Multivariate COX regression model was used to analyze the prognostic factors of TC patients. Results The positive rates of KDM1A (68.09％) and UCHL3 (65.96％) in cancer tissues were higher than those in adjacent tissues(10.64％,8.51％),and the differences were statistically significant(x2=64.984,66.369,all P<0.001). The protein expression of KDM1A and UCHL3 was significant protein correlation (r=0.714,P<0.001). The positive rates of KDM1A (87.50％,90.91％) and UCHL3 (85.00％,87.88％) in TNM stage Ⅲ～Ⅳ and lymph node metastatic TC cancer tissues were higher than those in stage Ⅰ～Ⅱ(53.70％,53.85％)and non-lymph node metastatic(55.74％,54.10％) cancer tissues,and the differences were statistically significant(x2=9.985～12.191,all P<0.001). The 5-year progression-free survival rates of TC patients in the KDM1A positive and negative groups were 62.50％ (40/64) and 86.67％ (26/30),with significant differences,the 5-year progression-free survival rates of UCHL3 positive and negative patients were 58.06％ (36/62) and 90.63％ (29/32),with significant differences (Log-Rankx2=5.670,9.724,P=0.017,0.002). KDM1A positive,UCHL3 positive,TNM stage Ⅲ～Ⅳ,lymph node metastasis were risk factors affecting the prognosis of TC patients (Waldx2=1.315～1.697,all P<0.001). Conclusion KDM1A and UCHL3 are upregulated in TC,and played a pro-cancer role. They are new tumor markers for evaluating the prognosis of TC patients.

Objective The purpose of this study is to investigate the expression of histone lysine-specific demethylase 1 (KDM1A) and ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) in thyroid cancer (TC) tissue and its relationship with clinical features and prognosis. Methods 94 TC patients diagnosed and treated at the Third Hospital of Heilongjiang Province from January 2017 to January 2019 were retrospectively selected as the study subjects. Immunohistochemistry was used to detect the expression of KDM1A and UCHL3 in tissues. Spearman correlation analysis was used to investigate the correlation between KDM1A and UCHL3. Kaplan-Meier survival curve was used to analyze the relationship between the levels of KDM1A and UCHL3 and the 5-year progression-free survival rate of TC patients. Multivariate COX regression model was used to analyze the prognostic factors of TC patients. Results The positive rates of KDM1A (68.09％) and UCHL3 (65.96％) in cancer tissues were higher than those in adjacent tissues(10.64％,8.51％),and the differences were statistically significant(x2=64.984,66.369,all P<0.001). The protein expression of KDM1A and UCHL3 was significant protein correlation (r=0.714,P<0.001). The positive rates of KDM1A (87.50％,90.91％) and UCHL3 (85.00％,87.88％) in TNM stage Ⅲ～Ⅳ and lymph node metastatic TC cancer tissues were higher than those in stage Ⅰ～Ⅱ(53.70％,53.85％)and non-lymph node metastatic(55.74％,54.10％) cancer tissues,and the differences were statistically significant(x2=9.985～12.191,all P<0.001). The 5-year progression-free survival rates of TC patients in the KDM1A positive and negative groups were 62.50％ (40/64) and 86.67％ (26/30),with significant differences,the 5-year progression-free survival rates of UCHL3 positive and negative patients were 58.06％ (36/62) and 90.63％ (29/32),with significant differences (Log-Rankx2=5.670,9.724,P=0.017,0.002). KDM1A positive,UCHL3 positive,TNM stage Ⅲ～Ⅳ,lymph node metastasis were risk factors affecting the prognosis of TC patients (Waldx2=1.315～1.697,all P<0.001). Conclusion KDM1A and UCHL3 are upregulated in TC,and played a pro-cancer role. They are new tumor markers for evaluating the prognosis of TC patients.

Objective:To analyze the epidemiological and etiological characteristics of herpes pharyngitis (HA) in three prefectures of Jiangsu Province, and provide evidence for the prevention and control of HA in Jiangsu.Methods:Three surveillance sentinel hospitals in Wuxi, Suzhou and Yancheng were selected from May 2018 to December 2022, and information related to HA visits and hospitalized cases was regularly collected from the hospital inpatient management system by age groups. Enterovirus nucleic acid detection was performed by RT-PCR, and sequencing analysis, identification of genotype subtypes, and phylogenetic analysis were performed on the sequences of the gene encoding the coat protein VP1 of the main prevalent strains.Results:A total of 57 709 HA cases were recorded in the sentinel hospitals in in Wuxi, Suzhou and Yancheng, which was 1.76 times higher than the reported cases of hand, foot and mouth disease during the same period (57 709/32 831).The percentage of HA hospitalizations was 1.35% (781/57 709), and the percentage of hospitalizations showed an increasing trend from year to year ( χ2=62.79, P<0.001 ).The incidence peak of HA was during May-July. The cases were mainly children aged 12-59 months (67.07%, 38 708/57 709), with the highest case number in age group 36-59 months (34.40%, 19 852/57 709). The HA positivity rate was 33.82% (644/1 904); enterovirus A was predominant (54.04%, 348/644); of these, Coxsackievirus (CV)A6 accounted for the highest percentage (52.59%, 183/348), while CVA16 and CVA4 accounted for 24.71% (86/348) and 15.23% (53/348), respectively. All 10 CVA4 HA endemic strains belonged to the C2 gene subtype, and all 6 CVA6 HA endemic strains belonged to the D3a gene subtype; and were genetically closer to and related to the strains in some areas of China (Fujian Province, Guangzhou City, Jiangxi Province, Yunnan Province, Tianjin City, etc.). Conclusions:The disease burden of HA was heavy in 3 areas in Jiangsu, children in age group 12-59-month were mainly affected, and the annual incidence peak of HA was during May-July. The pathogens causing HA varied, but predominated by enterovirus A and had low intra-typical differentiation, and no new evolutionary branches were found, suggesting that it is necessary to include HA in foot and mouth disease surveillance or regarded as a notifiable communicable disease.

By reviewing the historical materia medica， medical books and modern literature， this paper has systematically sorted out and verified the name， origin， quality and other aspects of Ophicalcitum. After herbal textual research， it is shown that before the Qing dynasty， the mineral medicine was mostly recorded in the name of Huarushi， but now it is called Huaruishi， and there is another mixed name Baiyunshi. The light white spots described in the historical materia medica are consistent with the characteristics of marble with sparkling star-like luster， combined with the color like sulfur， color are green， black spots and other serpentine features， it is deduced that it is serpentine marble， consistent with the present-day Ophicalcitum， and Ophicalcitum in the Song dynasty has a high content of serpentine. The main producing areas are Henan， Shaanxi， Shanxi and Sichuan， Jiangsu， Zhejiang， Hebei and other places are also available. Successive generations of materia medica on the quality evaluation of Ophicalcitum is less， the modern to neat and firm in the texture， sandwiched with yellow-green mottled for the best. Ophicalcitum is acidic， astringent and neutral in nature， belonging to the liver meridian， with the efficacy of treatment of gold sores and blood flow， internal leakage of cataracts， dropping afterbirth， now describing its efficacy as removing blood stasis and stopping bleeding. In ancient times， the earliest processing method was burning， followed by calcination by sulphur， calcination， quenching with vinegar and other methods. In modern times， it has been simplified to open calcination， processing with vinegar and the addition of water quenching. The gravimetric method and ethylenediaminetetraacetic acid titration were used to detect the contents of CO₃^2- and CaCO₃ in Ophicalcitum， respectively， and it was found that the gap in CaCO₃ content among commercially available products was wide， and the content of CaCO₃ in sample S13 and sample S18 was the same， but their compositions were different， and according to the contents of CO₃^2- and CaCO₃， the dolomite and calcite contents could be calculated， of which the higher the calcite content the more obvious the sparkling star-like luster. Raman spectroscopy and X-ray diffraction（XRD） were used to detect the physical phase composition of the powder of the samples， and Raman spectroscopy was used for the rapid non-destructive testing of the striped part， which showed that Ophicalcitum was mainly composed of dolomite， calcite， serpentine， olivine and pyroxene， with serpentine dominanting the striped part. In summary， the 2020 edition of Chinese Pharmacopoeia stipulates that the content of CaCO₃ in Ophicalcitum is not less than 40%， which is difficult to control its quality， and it is suggested to increase the detection of CO₃^2- content. This study can provide a scientific basis for the traceability of Ophicalcitum and better guide the clinical medication and rational utilization of resources.

Objective To investigate the effect and mechanism of Nuanxinkang on plaque formation in obstructive sleep apnea-hypopnea syndrome(OSAHS)comorbid with atherosclerosis(AS)mice by inhibiting endothelial-to-mesenchymal transition(EndMT).Methods Male ApoE-/-mice were randomly divided into six groups:control group,model group,atorvastatin group(2.6 mg·kg-1)and Nuanxinkang low-,medium-and high-dose groups(crude drug 3.5,7.0,14.0 g·kg-1),with eight mice in each group.The mice were exposed to chronic intermittent hypoxia(CIH)environment during sleep for a long time,and fed with high-fat diet to replicate OSAHS comorbid with AS mouse model.Oil red O staining was used to observe the formation of plaque on aortic intima in mice.Masson trichrome staining was used to evaluate the collagen content of atherosclerotic plaques in the aortic root of mice.The expressions of endothelial cell marker CD31 and EndMT marker Vimentin in aortic plaque were detected by immunofluorescence.Blood lipid levels were determined by ELISA;the mRNA expression levels of EndMT markers α-SMA and Cdh2 in aortic tissue were detected by qPCR.Results Compared with the control group,the area of aortic atherosclerotic plaque in the model group was significantly increased(P＜0.01),and the area of collagen deposition in the aortic root plaque was significantly increased(P＜0.01).The number of CD31 positive cells in the plaque were significantly decreased(P＜0.01),and the number of Vimentin positive cells were significantly increased(P＜0.01).Serum TG,T-CHO and LDL-C levels were significantly increased(P＜0.01),and HDL-C level was significantly decreased(P＜0.01).The mRNA expression levels of α-SMA and Cdh2 in aortic tissue were significantly increased(P＜0.01).Compared with the model group,the area of aortic atherosclerotic plaque in Nuanxinkang groups were significantly reduced(P＜0.05,P＜0.01),and the collagen deposition area of aortic root atherosclerotic plaque were significantly reduced(P＜0.05,P＜0.01).The number of CD31 positive expression cells in the plaque of Nuanxinkang high-dose group were significantly increased(P＜0.05),and the number of Vimentin positive expression cells in the plaque of Nuanxinkang medium-and high-dose groups were significantly decreased(P＜0.05,P＜0.01).The serum TG level of mice in the high-dose group of Nuanxinkang was significantly decreased(P＜0.01).The serum T-CHO and LDL-C levels of mice in each Nuanxinkang administration group were significantly decreased(P＜0.05,P＜0.01).The serum HDL-C levels of mice in the medium-and high-dose groups of Nuanxinkang were significantly increased(P＜0.01).The mRNA expression levels of α-SMA and Cdh2 in aortic tissue of mice in each treatment group were significantly decreased(P＜0.01).Conclusion Nuanxinkang can effectively reduce the plaque formation in OSAHS comorbid with atherosclerosis mice,which may be related to its inhibition of EndMT and reduction of collagen fiber formation.

Objective:To investigate the application value of transanal endoscopic intersphincteric resection (taE-ISR) in sphincter preservation for low rectal cancer.Methods:The pro-pensity score matching and retrospective cohort study was conducted. The clinicopathological data of 278 patients with low rectal cancer who were admitted to 5 medical centers, including Ruijin Hospital of Shanghai Jiaotong University School of Medicine et al, from January 2017 to December 2021 were collected. There were 178 males and 100 females, aged 58 (range, 49-64)years. Of 278 pati-ents, 147 cases undergoing taE-ISR were divided into the taE-ISR group, and 131 cases undergoing intersphincteric resection (ISR) were divided into the ISR group. Observation indicators:(1) propen-sity score matching and comparison of general data of patients between the two groups after matching; (2) comparison of intraoperative and postoperative conditions between the two groups; (3) long-term follow-up of the two groups; (4) analysis of risk factors affecting sphincter preservation for low rectal cancer. Propensity score matching was done by the 1∶1 nearest neighbor matching method, with a caliper value of 0.05. Propensity score matching analysis was done using the Matching package. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the Student′s t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the Pearson chi-square test or Fisher exact probability. The Kaplan-Meier method was used to calculate survival rate and plot survival curve, and the Log-Rank test was used for survival analysis. Multivariate analysis was conducted using the Logistic regression model with the "glm2" package. The forest plot was used to show the risk factors affecting sphincter preservation for low rectal cancer. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of 278 patients, 180 cases were successfully matched, including 90 cases in the taE-ISR group and 90 cases in the ISR group, respectively. After propensity score matching, the elimination of distance between ischial tuberosities and distance from ischial tuberosity to the skin of buttocks confounding bias ensured comparability between the two groups. (2) Comparison of intraoperative and postoperative conditions between the two groups. Cases with positive distal margins, cases with specimen integrity, cases with sphincter preservation were 1, 88, 88 in the taE-ISR group and 8, 78, 74 in the ISR group, showing significant differences between the two groups ( P<0.05). (3) Long-term follow-up of the two groups. The median follow-up time was 4.3(range, 3.8-5.0)years of the taE-ISR group and 4.1(range, 3.4-4.7)years of the ISR group. The overall survival rate, disease-free survival rate and cumulative recurrence rate were 100.0%, 95.6% and 2.2% of the taE-ISR group, versus 98.9%, 87.8% and 10.0% of the ISR group, showing no significant difference in overall survival rate between the two groups ( χ2=0.97, P>0.05) and significant differences in disease-free survival rate and cumulative recurrence rate between the two groups ( χ2=4.05, 5.26, P<0.05). (4) Analysis of risk factors affecting sphincter preservation for low rectal cancer. Results of multivariate analysis showed that taE-ISR, distance from the tumor to the anus, and adjacent organ damage were independent factors affecting sphincter preservation for low rectal cancer ( odds ratio=0.86, 0.88, 1.35, 95% confidence interval as 0.79-0.93, 0.83-0.92, 1.04-1.74, P<0.05). In further analysis, there were significant differences in sphincter preservation and defecatory dysfunction between the 21 cases with neoadjuvant therapy in the taE-ISR group and the 19 cases with neoadjuvant therapy in the ISR group ( P<0.05). Conclusions:The taE-ISR is safe and feasible for patients with low rectal cancer. Compared with ISR, taE-ISR can significantly improve surgical quality, sphincter preservation rate and patient prognosis.

【Objective】 To investigate the feasibility of prostatic exosomal protein (PSEP) detection kit in the diagnosis of histological prostatitis (HP) in patients with benign prostatic hyperplasia (BPH), and to explore the correlation between PSEP and other clinical parameters. 【Methods】 A total of 104 patients with BPH or BPH plus HP treated during Nov.2021 and Nov.2022 were involved. The patients were instructed to fill out the International Prostate Symptom Score (IPSS) scale independently before surgery. Clinical data such as prostate volume, residual urine volume, free prostate specific antigen (fPSA), total prostate specific antigen (tPSA), and fPSA/tPSA were collected. Preoperative midstream morning urine was collected for PSEP detection. 【Results】 The sensitivity and specificity of PSEP in the diagnosis of BPH were 93.51% and 70.37%, respectively, which were highly consistent with the postoperative pathological diagnosis results (Kappa=0.663). Serum PSEP level was positively correlated with tPSA level (r=0.242, P=0.040). 【Conclusion】 PSEP has a high clinical diagnostic value in the diagnosis of HP, which can provide a reliable basis for the diagnosis of HP in BPH patients and improve the diagnosis rate.

A series of chemotherapeutic drugs that induce DNA damage, such as cisplatin (DDP), are standard clinical treatments for ovarian cancer, testicular cancer, and other diseases that lack effective targeted drug therapy. Drug resistance is one of the main factors limiting their application. Sensitizers can overcome the drug resistance of tumor cells, thereby enhancing the antitumor activity of chemotherapeutic drugs. In this study, we aimed to identify marketable drugs that could be potential chemotherapy sensitizers and explore the underlying mechanisms. We found that the alcohol withdrawal drug disulfiram (DSF) could significantly enhance the antitumor activity of DDP. JC-1 staining, propidium iodide (PI) staining, and western blotting confirmed that the combination of DSF and DDP could enhance the apoptosis of tumor cells. Subsequent RNA sequencing combined with Gene Set Enrichment Analysis (GSEA) pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism: DSF makes cells more vulnerable to DNA damage by inhibiting the Fanconi anemia (FA) repair pathway, exerting a sensitizing effect to DNA damaging agents including platinum chemotherapy drugs. Thus, our study illustrated the potential mechanism of action of DSF in enhancing the antitumor effect of DDP. This might provide an effective and safe solution for combating DDP resistance in clinical treatment.
Female ; Male ; Humans ; Cisplatin/pharmacology* ; Disulfiram/pharmacology* ; Testicular Neoplasms/drug therapy* ; Fanconi Anemia/drug therapy* ; Alcoholism/drug therapy* ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; Substance Withdrawal Syndrome/drug therapy* ; Apoptosis ; Antineoplastic Agents/therapeutic use* ; Cell Proliferation