Huaihuasan， first recorded in Experiential Prescriptions for Universal Relief （Pu Ji Ben Shi Fang）， is a classic prescription for the treatment of ''hematochezia due to intestinal wind''. In 2018， it was included by the National Administration of Traditional Chinese Medicine as one of the first 100 classic prescriptions. This formula consists of four ingredients， i.e.， Sophorae Flos， Platycladi Cacumen， Schizonepetae Spica， and Aurantii Fructus. It is known for its ability to clear the intestines， dispel wind， cool the blood， and stop bleeding. In modern clinical practice， Huaihuasan， often with modifications， is widely used to treat various digestive tract diseases， including ulcerative colitis （UC）， with significant long-term effects. UC is a chronic， non-specific inflammatory bowel disease. Currently， Western medicine primarily treats UC with glucocorticoids， aminosalicylates， and immunosuppressants， which have good short-term efficacy but numerous adverse reactions， high recurrence rates， and the need for lifelong medication. Modern clinical studies have shown that Huaihuasan can significantly improve symptoms of UC， such as abdominal pain and diarrhea， reduce disease activity scores （Sutherland）， promote intestinal mucosal healing， alleviate anxiety and depression， and significantly improve the quality of life of patients. Pharmacological studies have shown that the main active components of Huaihuasan include quercetin， rutin， kaempferol， naringenin， and volatile oils. These compounds exert their effects by inhibiting inflammatory responses and protecting the intestinal mucosal barrier. They also exhibit antioxidant properties and regulate various signaling pathways， including tumor necrosis factor-α （TNF-α）， interleukin-2 （IL-2）， interleukin-4 （IL-4）， interleukin-1β （IL-1β）， monocyte chemoattractant protein-1 （MCP-1）， nuclear factor-κB （NF-κB）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， and the KRAS-regulated mitogen-activated protein kinase （MEK）-extracellular signal-regulated kinase （ERK） pathway. These multi-target pathways improve UC symptoms， inhibit inflammation-cancer transition， and help maintain intestinal homeostasis. However， the precise mechanism of action has not yet been systematically elucidated. This paper reviews the research progress on Huaihuasan and main ingredients from its component drugs， focusing on their effects against UC. It also discusses current research limitations and suggests strategies for improvement， aiming to provide a reference for further studies on Huaihuasan in the treatment of UC and the development of new drugs.

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

ObjectiveTo explore the function of DANCR during the differentiation of human embryonic stem cells （hESC） toward definitive endoderm （DE）. MethodsThe in vitro DE differentiation system was established and its efficiency was verified. The correlation between the expression level of DANCR and DE differentiation process was detected. Using lentivirus system， we stably knocked down DANCR in hESC. The shDANCR hESC line was applied to DE differentiation， using qPCR and Western blot to detect the expression of DE marker genes SOX17 and FOXA2， and that of primitive streak marker genes Brachyury （T）， EOMES， MIXL1 and GSC. Dual luciferase reporter assay and qPCR were used to confirm the interaction between DANCR and the WNT pathway during DE differentiation. ResultsThe in vitro differentiation system mimicked DE differentiation efficiently. And the expression of DANCR was gradually downregulated during differentiation. DANCR was efficiently knocked down in the shDANCR hESC line （P < 0.001）. Compared with those in the control group， the expression levels of primitive markers Brachyury （T）， EOMES， MIXL1 and GSC， as well as DE markers SOX17 and FOXA2， were significantly decreased in shDANCR groups （P < 0.05）. Furthermore， the transcriptional activity of the WNT pathway in shDANCR groups was lower than that in the control group （P < 0.05）. And RNA levels of downstream genes of the WNT pathway， FZD5， FZD8， SFRP1， FRZB and ANKRD6， were significantly decreased in shDANCR groups （P < 0.05）. However， differences in protein levels of the TGFβ pathway effectors SMAD2/3 and p-SMAD2 were statistically insignificant in shDANCR and control groups （P > 0.05）. Forced activation of β-CATENIN rescued DANCR knock down-induced deficiency in DE differentiation. ConclusionsThe expression of DANCR decreases during DE differentiation. DANCR may promote DE differentiation through modulating the activity of the WNT pathway.

Objective To investigate the related factors and prevention measures of postoperative fever in patients with renal cyst.Methods Retrospective analysis was made on the clinical data of 150 patients who were treated with laparoscopic renal cyst decapitation and decompression and sclerotherapy in Hangzhou First People's Hospital from January 2018 to December 2021,including age,gender,location,diameter,preoperative non gonococcal urethritis,preoperative urine culture,preoperative urinary leukocytes,hypertension,diabetes,operation mode,postoperative blood C reactive protein(CRP),and postoperative blood leukocytes,The time of onset of fever and the highest temperature of fever in patients with renal cysts after surgery were recorded.The patients were divided into fever group and non fever group after surgery.The related factors and causes of fever in the two groups were analyzed.Results Postoperative fever occurred in 121 cases(80.7%).There were statistically significant differences in gender ratio,diabetes history,preoperative routine urine white blood cell count,preoperative urine culture,preoperative non-gonococcal urethritis and surgical methods between the two groups(P<0.05).Logistic multivariate analysis showed that the history of diabetes mellitus and preoperative concomitant non-gonococcal urethritis were independent risk factors for postoperative fever(OR>1,P<0.05),postoperative blood CRP difference was statistically significant(P<0.05),postoperative fever was related to infection.Conclusion Patients with renal cyst need routine urine bacterial culture and routine urine white blood cell count before surgery to thoroughly treat urinary tract infection.Renal cyst sclerotherapy is selected to reduce the incidence of postoperative fever.History of diabetes mellitus and non-gonococcal urethritis were independent risk factors for fever after renal cyst.

Objective:To evaluate our self-designed pubic symphysis orthotic compression anatomic plate (PSOCAP) in the treatment of fractures and dislocations around the pubic symphysis.Methods:A retrospective study was conducted to analyze the 16 patients with fracture or dislocation around the pubic symphysis who had been treated by our self-designed PSOCAP at Department of Traumatic Surgery, Center for Orthopaedic Surgery, The Third Hospital Affiliated to Southern Medical University from January 2021 to June 2022. There were 8 males and 8 females with an age of (41±19) years. According to the Tile classification for pelvic fractures, there were 3 cases of type B1, 2 cases of type B3, 1 case of type C1.2, 4 cases of type C1.3, 3 cases of type C2, and 3 cases of type C3. There were 8 cases of pubic symphysis separation and 8 fractures of the pubic ramus (2 ones at Nakatani zone Ⅰ and 6 ones at Nakatani zone Ⅱ). Time from injury to surgery was 16 (11, 53) days, ranging from 4 to 348 days. The fractures or dislocations around the pubic symphysis were exposed by the modified Stoppa approach, reduced with the assistance of PSOCAP and fixated with PSOCAP; the posterior pelvic ring was reduced and fixated by corresponding surgical methods. Recorded were the surgical time, intraoperative bleeding, postoperative quality of fracture reduction, surgical complications, and functional recovery at the last follow-up concerning the pelvic anterior ring.Results:Surgery went on successfully in the 16 patients. Their surgical time was (58±15) min, ranging from 40 to 90 min, and their intraoperative bleeding 85 (63, 150) mL, ranging from 50 to 250 mL. According to the Matta scoring, the fracture reduction was evaluated as excellent in 10 cases, as good in 3 cases and as fair in 3 cases. The (10±3)-month follow-up for the 16 patients revealed complete fracture union for all after (12±2) weeks. According to the Majeed scoring at the last follow-up, the pelvic function was evaluated as excellent in 5 cases, as good in 7 cases, and as fair in 4 cases. No such postoperative complications as fracture displacement or internal fixation failure occurred.Conclusion:Owing to the biplane and integrated structure, our self-designed PSOCAP can help reduce the fractures or dislocations around the pubic symphysis to achieve anatomical reduction and strong internal fixation, leading to good clinical efficacy.

Adventitia ; Atherosclerosis/genetics* ; Cell Communication ; Humans ; Hyperhomocysteinemia/genetics* ; Sequence Analysis, RNA

Objective:To investigate the relationship between double mutations of myosin heavy chain gene (MYH6) p.Gly743Arg and p.Glu1389Lys and the cardiac phenotype.Methods:Patients carrying double mutations in the MYH6 gene p.Gly743Arg and p.Glu1389Lys were screened from 52 unrelated left ventricular hypertrophy (LVH) who were admitted to the Second Hospital of Chongqing Medical University from 2015 to 2020, and the genetic testing of peripheral blood of patients by second-generation whole-exome sequencing assay technology and genomic DNA of their family members Sanger sequencing was performed to validate the genomic DNA of the family members. The cardiac phenotype was evaluated by electrocardiogram, coronary computed tomography angiography (CTA), echocardiography, and cardiac magnetic resonance imaging (MRI) as adjuncts.Results:All whole-exome gene were detected in 52 unrelated patients with LVH, of which 1 patient (1.9%) had double mutations in MYH6 gene p.Gly743Arg and p.Glu1389Lys (proband). Two members of the maternal line of this patient carried p.Glu1389Lys mutation, but there was no obvious clinical phenotype. Two members of the paternal line carried p.Gly743Arg mutation and had obvious clinical phenotype of bradycardia, but there was no LVH. The male proband, aged 21 years old, presented with LVH and sinus bradycardia but no coronary artery stenosis on CTA before treatment, MRI showed that the left ventricular end diastolic diameter was 58 mm. After treatment with angiotensin receptor-enkephalinase inhibitor (ARNI), electrocardiogram showed that the heart rate increased significantly (from 43 bpm to 72 bpm). Echocardiography showed that the left ventricular end diastolic diameter decreased significantly (from 60 mm to 49 mm).Conclusions:The p.Glu1389Lys mutation of the MYH6 gene may not manifest the phenotype of heart disease. MYH6 gene p.Gly743Arg mutation may be manifested asymptomatic sinus bradycardia, but there is no LVH phenotype. The cardiac disease phenotype caused by the double mutations of p.Gly743Arg and p.Glu1389Lys in the MYH6 gene is more obvious. Asymptomatic LVH and sinus bradycardia can appear in adolescence, but the LVH phenotype can be reversed in a short period of time after ARNI treatment.

Objective: To further explore TCE-induced hepatotoxicity and its mechanisms by identification of trichloroethylene (TCE) induced abnormal histone methylation in human liver cells. Methods: L-02 cells were treated with 0 and 8 mmol/L TCE for 24 h. Histones were extracted by acid. Liquid chromatography electrospray ionization tandem mass spectrometry (ESI-LC-MS/MS) were used to identify and quantify TCE related histone methylations. TCE induced abnormal methylation of H3K79 me2 and H3K79 me3 were validated by Western blot analysis. The further analysis of the function of histone abnormal methylation modifications were done by single cell gel electrophoresis (SCGE) and Western blot analysis of p53 and ɤH2AX. Results: After treatment with TCE for 24 h in L-02 cells, the 36 TCE related histone methylation sites in 28 peptide segments were identified by MS. After treatment with TCE in concentrations of 0 and 8.0 mmol/L in L-02 cells for 24 h, the relative expression level of histone H3K79 me3 were 1.00±0.06, 0.70±0.09 (t=15.01, P=0.015); the relative expression level of histone H3K79 me2 were 1.00±0.05, 0.74±0.07 (t=16.69, P=0.018); the Olive Tail Moment about DNA damage were 1.46±0.28, 3.12± 0.68 (t=15.22, P=0.018); the relative expression levels of p53 were 1.00±0.04, 1.24±0.04 (t=18.71, P= 0.012); and the relative expression levels of ɤH2AX were 1.00 ± 0.03, 1.56 ± 0.11 (t=8.32, P=0 045). Conclusion TCE can induce changes in the relative expression level of H3K79 me2 and H3K79 me3 in L-02 cell, and induce DNA damage, suggesting that TCE may induce changes in the relative expression level of H3K79 me2 and H3K79 me3 by DNA damage.

Objective To explore the influence of the scores and weights of the regular grade on the evaluation of students' learning effect.Method To compare the impact of the regular grade before and after adjustment on the total mark,analyze the problems exposed during scoring and search for the solutions according to Medical Microbiology results of four grades including Grade 2010 to 2013.SPSS 13.0 software was used for statistical analysis and Pearson method was used for correlation analysis and theory achievement scores.Results The regular grade of four grades scored highly,with the average (95.00 ± 3.80),(96.00 ± 4.55),(95.00 ± 2.84) and (95.00 ±-2.82) respectively.What was more,it had randomness.The correlation coefficient between regular grade and total mark were 0.069,0.149,0.984 and 0.285 respectively.The regular grade of Grade 2010 was the same as Grade 2013 and the theoretical score of Grade 2013 was 4 points lower than Grade 2010(71 vs.75),however the total mark of Grade 2013 was 1 point higher than Grade 2010 (80 vs.79),which showed the more the regular grade weights,the greater it impacted on the total mark.Conclusion The appropriate score and weight of the regular grade is important to evaluate the students' learning effect objectively.

OBJECTIVETo study postoperative anorectal dynamic change in ultra-low rectal cancer patients undergoing laparoscopic intersphincteric resection.

METHODSClinical and follow-up data of 26 ultra-low rectal cancer patients undergoing laparoscopic intersphincteric resection in our department from January 2007 to January 2013 were retrospectively analyzed (observation group). Thirty rectal cancer patients undergoing laparoscopic low anterior resection by the same surgical team in the same period from the Medical Record Room were randomly extracted as control group. The observation indexes included preoperative and postoperative anal resting pressure(ARP), anal maximum squeeze pressure (AMSP), rectal maximum tolerable volume (RMTV), rectal anal inhibition reflex (RAIR) and Wexner anal function scores (0 means normal).

RESULTSThere were no significant differences in clinical baseline data between the two groups(all P>0.05), except the distance from lower edge of tumor to dentate line [(2.9±0.4) cm in observation group vs. (5.0±0.5) cm in control group, P=0.000]. There were no differences in preoperative anorectal manometry and Wexner anal function score between two groups (all P>0.05). The average follow-up time in observation group and control group was 14.5 months and 14.0 months respectively. Three months after operation, significant differences between observation group and control group (all P=0.000) were as follows: defecation frequency [(6.0±1.5) times/day vs. (2.5±1.0) times/day], Wexner anal function score(5.0±0.9 vs. 2.9±1.2), ARP [(32.0±6.7) mmHg vs. (45.0±8.2) mmHg], AMSP [(90.1±6.9) mmHg vs. (110.0±7.5) mmHg], RMTV [(61.0±7.2) ml vs. (91.1±7.5) ml] and positive rate of RAIR [11.5%(3/26) vs. 66.7%(20/30)]. One year after surgery, there were no significant differences in defecation frequency, Wexner anal function scores, ARP, AMSP and RMTV between the two groups (all P>0.05), however the difference in positive rate of RAIR was still significant[38.5%(10/26) vs. 93.3%(28/30), P=0.000].

CONCLUSIONLaparoscopic intersphincteric resection for ultra- low rectal cancer can achieve satisfactory anorectal dynamic effect.

Aged ; Anal Canal ; physiopathology ; Female ; Humans ; Laparoscopy ; Male ; Middle Aged ; Postoperative Period ; Pressure ; Rectal Neoplasms ; surgery ; Rectum ; physiopathology ; Retrospective Studies