ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled， and according to the presence or absence of esophageal and gastric varices under gastroscopy， they were divided into esophageal and gastric varices group （GOV group） and non-esophageal and gastric varices group （NGOV group）. Related data were collected， including age， sex， imaging findings， and laboratory markers. The chi-square test was used for comparison of categorical data between groups； the least significant difference t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic （ROC） curve was plotted to evaluate the diagnostic value of five scoring models， i.e.， fibrosis-4 （FIB-4）， LOK index， LPRI， aspartate aminotransferase-to-platelet ratio index （APRI）， and aspartate aminotransferase/alanine aminotransferase ratio （AAR）. The binary logistic regression method was used to establish a combined model， and the area under the ROC curve （AUC） was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group， the GOV group had a significantly higher age （52.64±1.44 years vs 47.96±1.68 years， t=0.453， P<0.05） and significantly lower levels of alanine aminotransferase ［42.00 （24.00 — 17.00） U/L vs 82.00 （46.00 — 271.00） U/L， Z=-3.065， P<0.05］， aspartate aminotransferase ［44.00 （32.00 — 96.00） U/L vs 62.00 （42.50 — 154.50） U/L，Z=-2.351， P<0.05］， and platelet count ［100.00 （69.00 — 120.00）×10⁹/L vs 119.00 （108.50 — 140.50）×10⁹/L， Z=-3.667， P<0.05］. The ROC curve analysis showed that FIB-4， LOK index， LPRI， and AAR used alone had an accuracy of 0.667， 0.681， 0.730， and 0.639， respectively， in the diagnosis of esophageal and gastric varices （all P<0.05）， and the positive diagnostic rates of GOV were 69.97%， 65.28%， 67.33%， and 58.86%， respectively， with no significant differences in AUC values （all P>0.05）， while APRI used alone had no diagnostic value （P>0.05）. A combined model （LAF） was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%， with a significantly higher AUC than FIB-4， LOK index， LPRI， and AAR used alone （Z=-2.773，-2.479，-2.206， and-2.672， all P<0.05）. ConclusionFIB-4， LOK index， LPRI， and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy， which provides a certain reference for clinical promotion and application.

Breast cancer (BC) is one of the most prevalent malignant tumors affecting women worldwide, with its incidence rate continuously increasing. As a result, treatment strategies for this disease have received considerable attention. Research has highlighted the crucial role of the Hedgehog (Hh) signaling pathway in the initiation and progression of BC, particularly in promoting tumor growth and metastasis. Therefore, molecular targets within this pathway represent promising opportunities for the development of novel BC therapies. This study aims to elucidate the therapeutic mechanisms by which natural compounds modulate the Hh signaling pathway in BC. By conducting a comprehensive review of various natural compounds, including polyphenols, terpenes, and alkaloids, we reveal both common and unique regulatory mechanisms that influence this pathway. This investigation represents the first comprehensive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC. Furthermore, by exploring the structure-activity relationships between these compounds and their molecular targets, we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway. These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics. Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.

Objective To investigate the effect of daily soft brace wearing on plantar dynamics during walking in patients with chronic ankle instability(CAI). Methods A total of 52 patients with unilateral chronic ankle instability(CAI)in Beijing Rehabilitation Hospital from February,2021 to January,2023 were randomly divided into control group(n=26)and experimental group(n=26).Both groups underwent an eight-week exercise training program.The control group wore placebo brace dur-ing daily activities,while the experimental group wore soft ankle brace.Plantar dynamic parameters were mea-sured using a pressure plate system during walking,including peak plantar pressure and plantar impulse before and after intervention. Results Six participants dropped out in the control group and five in the experimental group,resulting in a final inclu-sion of 41 participants.After intervention,there was no significant difference in peak plantar pressure and im-pulse on the affected side in the control group among different areas(P＞0.05).In the experimental group,the peak pressure and impulse in the heel medial,heel lateral and forefoot medial areas increased(|t|＞4.192,P＜0.001),while the peak pressure and impulse in the midfoot and lateral forefoot areas decreased(t＞2.984,P＜0.05);the peak pressure and impulse in the heel medial,heel lateral and forefoot medial areas were higher in the experimental group than in the control group(|t|＞2.126,P＜0.05),and the peak pressure and impulse were low-er in the midfoot and forefoot lateral areas(t＞2.133,P＜0.05). Conclusion Wearing a soft brace during daily activities may optimize the distribution of peak plantar pressure and plan-tar impulse on the affected side in patients with CAI,which may prevent recurrence of sprains.

Objective:To retrospectively analyze and summarize the clinical experience and therapeutic effect of anterograde Needle-perc combined with RIRS, namely N+ R (Needle perc + RIRS) technique in the treatment of complex calyceal diverticular stone.Methods:Retrospective analysis of 23 cases of complex renal caliceal diverticulum stones admitted to our hospital from January 2020 to December 2022. The complex factors mainly include the invisible cervical orifice of diverticulum, large stone volume, and special anatomical location, which makes single RIRS or PCNL treatment difficult or unsuccessful. There were 14 males and 9 females with an average age of (42.3±6.1) years. Three cases were upper calyceal diverticular stone, average size was (0.9±0.2)cm. Nine patients had diverticular stone in the middle posterior calyx, and the average size was (1.2±0.3)cm. The average size of four diverticular stone was (1.8±0.2)cm in the anterior middle calyx. Seven patients had diverticular stone with an average size of (1.3±0.1)cm in lower calyx. Among them, 12 patients underwent RIRS which were difficult or stone undiscovered, and 3 patients underwent PCNL and the operation was terminated due to failure of channel establishment. In our center, oblique supine lithotomy position (male) or prone split-leg position (female) was adopted, and the combined treatment of Needle-perc and RIRS was performed. Needle-perc puncture was completed under the guidance of full ultrasound. During the operation, methylene blue reagent or mutual guidance of two endoscopes was used to find the diverticulum neck and expand the outlet with holmium laser incision. Depending on the size and location of the stones, a single Needle-perc laser lithotripsy combined with stone removal in flexible ureteroscope was used, or dual lasers were be used simultaneously for stone removal under double endoscopes. The first stage stone free rate, operation time, hemoglobin decrease, complications, postoperative hospital stay and other conditions were analyzed.Results:All the 23 operations were completed successfully. The stone free rate within 48 hours and one month after surgery was 78.2% and 100.0% respectively. The average operation time was (61.5±12.2)min. The mean postoperative hospital stay was (2.8±0.6) days. The mean decrease of hemoglobin was (3.6±0.4)g/L. Three patients had fever and one patient had renal subcapsular effusion. After anti-inflammatory and symptomatic treatment, the patient was discharged. There was no incidence of Clavien-Dindo≥Ⅱcomplications such as blood transfusion, abdominal organ injury or urosepsis.Conclusions:Treatment of complex renal caliceal diverticulum stones using N+ R technique of anterograde needle-perc combined with RIRS can effectively improve the success rate of first-stage surgery. Overall, it is safe, efficient and feasible with the advantages of high stone free rate, lower damage, and few postoperative complications.

Objective To analyze the relationship between expression levels of long non-coding RNA(LncRNA)LINC00342 and microRNA-203a-3p(miR-203a-3p)in colorectal cancer tissue and the prognosis of patients within 5 years after surgery.Methods Samples of colorectal cancer tissue and paracancer tissue of 133 patients with colorectal cancer were collected.Expression levels of LncRNA LINC00342 and miR-203a-3p were detected by fluorescence quantitative PCR.Survival and death were recorded after 5 years of follow-up.The LncRNA LINC00342 and miR-203a-3p expressions and clinicopathological parameters in patients under different conditions were compared.The correlation between expressions of LncRNA LINC00342 and miR-203a-3p in colorectal cancer tissue was analyzed,and their predictive value for the prognosis was also analyzed.Results The expression level of LncRNA LINC00342 was higher in colorectal cancer tissue than that in paracancer tissue,and the expression level of miR-203a-3p was lower in colorectal cancer tissue than that in paracancer tissue(P＜0.05).The expression levels of LncRNA LINC00342 and miR-203a-3p in colorectal cancer tissue were negatively correlated(P＜0.05).The proportion of patients with low tumor differentiation,TNM stage Ⅲ and lymph node metastasis were higher in the LncRNA LINC00342 high expression group and the miR-203a-3p low expression group than those in the LncRNA LINC00342 low expression group and the miR-203a-3p high expression group,respectively(P＜0.05).The 5-year overall survival rate after operation was lower in the LncRNA LINC00342 high expression group and the miR-203a-3p low expression group(P＜0.05).The proportion of patients with low tumor differentiation,TNM stage Ⅲ,lymph node metastasis,and higher expression level of LncRNA LINC00342 were higher in colorectal cancer tissue of the death group than those in the survival group,and the expression level of miR-203a-3p was lower than that in the survival group(P＜0.05).Low tumor differentiation,TNM stage Ⅲ,lymph node metastasis,high expression of LncRNA LINC00342 and low expression of miR-203a-3p were independent risk factors for death within 5 years after colorectal cancer surgery(P＜0.05).The combined predictive value of LncRNA LINC00342 and miR-203a-3p for prognosis was greater than that of individual prediction.Conclusion LncRNA LINC00342 is higher expressed and miR-203a-3p is lower expressed in colorectal cancer tissue,and the combined detection of the two is expected to become a clinical evaluation indicator for predicting postoperative survival.

Objective:To prepare recombinant protein of group 36 allergen of Dermatophagoides farinae(Der f 36),to deter-mine its immunogenicity and bioinformatics analysis was performed.Methods:Nucleic acid sequence coding for Der f 36 was obtained and artificially synthesized,pET-28a(+)was inserted to construct pET-28a(+)-Der f 36 plasmid and transformed into BL21(DE3)receptor cells.After expressed and purified in BL21(DE3),recombinant allergen rDer f 36 was obtained,recombinant protein rDer f 36 was identified by SDS-PAGE and Western blot.Serum IgE binding rates of rDer f 36 was determined by IgE-ELISA.Cross-reactivity between rDer f 36 and rDer p 36 was detected by IgE-ELISA inhibition assay.HNEpC cells were cultured with rDer f 36 for 24 h and cytokines were detected.Bioinformatics softwares were used to analyze physicochemical properties and structures of Der f 36 and Der p 36.Results:Coding gene for Der f 36 was obtained with a total length of 690 bp,whose molecular weight was 25.6 kD;serum IgE binding rate of rDer f 36 was 42.1%by IgE-ELISA;IgE-ELISA inhibition assay showed that rDer p 36 had 40%(8/20)inhibition rate(>50%)for rDer f 36,with an average inhibition rate of 52.98%.Compared with control group,HNEpC cells cultured with rDer f 36 showed that IL-6,IL-8,IL-33,IL-25 and TSLP expressions had increased;bioinformatics analyses show that sequence consistency of Der f 36 and Der p 36 was 77.63%,with similar physicochemical properties.Secondary structure analysis showed that both of them contained α helix,β-turn and random coils,and content of random coils was the highest;structure of C2 domains was also highly overlapping(RMSD=0.046).Conclusion:Recombinant allergen rDer f 36 is successfully prepared with good immunogenicity,laying foundation for diagnosis and treatment of dust mite allergen single component.High similarity in physical and chemical properties,secondary structure,and tertiary structure between Der f 36 and Der p 36 determines their cross reactivity.

Objective:To retrospectively summarize disease characteristics and the clinical experience of minimally invasive endoscopy in the treatment of upper urinary tract obstruction caused by ureteropelvic encrusted inflammatory disease.Methods:Three patients with bilateral ureteropelvic encrusted inflammatory disease admitted to our hospital from March 2018 to July 2021 were involved. Case 1, male, 45 years old, admitted due to bilateral hydronephrosis for 5 months. The preoperative diagnosis were bilateral ureteropelvic stones (encrustation), right ureteral atresia, left ureteral stenosis, and systemic vasculitis. Left double J tube insertion and right nephrostomy were performed in another hospital. We conducted antegrade percutaneous nephroscopy combined with retrograde ureteroscopy surgery and assisted balloon dilation to treat bilateral lesions stage by stage. Case 2, Male, 12 years old, admitted due to bilateral abdominal pain for 6 weeks. The preoperative diagnosis were bilateral ureteral stones, bilateral hydronephrosis, and dermatomyositis. After the failure of double J tube insertion in another hospital, double nephrostomy was performed instead. We performed left percutaneous nephroscopy and right percutaneous nephroscopy combined with ureteroscopy for the treatment of bilateral lesions. Case 3, female, 32 years old, was admitted because of pain in the left lower back and abdomen for over 6 months. The preoperative diagnosis were bilateral ureteral stones, bilateral ureteral stenosis, and dermatomyositis. She underwent three times of ESWL and once URS before. We performed ureteroscopic surgery for bilateral lesions. During the surgery, various degrees of crusting in the renal pelvis or ureter were observed in all 3 cases, and the lesions were removed using pneumatic lithotripsy combined with forceps or baskets. After surgery, oral antibiotics were continuously used for 1-3 months. The efficacy and prognosis were evaluated based on the follow-up of urine, imaging, and endoscopic examinations at 3, 6, and 12 months after surgery.Results:All 3 surgeries were successfully completed. At 3, 6, and 12 months after surgery, follow-up CT showed no crusting in the left ureter, and endoscopy showed good mucosal wound healing and unobstructed lumen in case 1. There were still some crusting lesions and lumen stenosis in the right renal pelvis, and the right ureter reconstruction surgery was ultimately performed. There were no crusting on both sides and the urinary tract was unobstructed after 3, 6, and 12 months of follow-up in case 2 and case 3. Postoperative pathological examination showed chronic inflammation of urothelial mucosal tissue, small pieces of proliferative fibrous tissue with peripheral calcification. Calcification layer composition analysis showed magnesium ammonium phosphate and carbonate apatite. No related complications occurred in case 2 and case 3.Conclusions:Urothelial crusted inflammatory disease is rare clinically, and the diagnosis and treatment strategies are rarely reported domestically and internationally. Preoperative imaging examination, intraoperative findings and postoperative pathology or calcification composition analysis are of instruction for the diagnosis and treatment of this disease. Minimally invasive endoscopy treatment for upper urinary tract obstruction caused by ureteropelvic encrusted inflammatory disease has a good effect. Long-term efficacy and other adjuvant treatment need long-term follow-up and clinical practice.

Objective:To summarize the preliminary clinical experience of utilizing ureteral balloon dilation catheter in the treatment of "difficult ureter" during ureteroscopic lithotripsy, and to discuss the efficacy and safety of the technique.Methods:Clinical data of 28 patients (30 sides) with upper urinary tract calculi admitted to Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua University from April 2021 to July 2022 were retrospectively analyzed. There were 23 males (82.1%) and 5 females (17.9%), with age of (51.5±13.6) years. Among the 30 sides, 20 (66.7%) on the left and 10(33.3%) were on the right. Calculi were either located in the renal pelvis or calyxes in 7 sides (23.3%), upper ureter in 17 sides (56.7%), and lower ureter in 6 sides (20.0%). The maximum diameter of the stones was (9.4±4.2)mm, and 23 sides (76.7%) were combined with hydronephrosis before surgery. When "difficult ureter" was encountered during the procedure, that is, it was difficult to insert ureteroscope or ureteral access sheath (UAS) due to small ureteral lumen, balloon catheter was used for dilation in the first stage, in which the balloon diameter was 4 mm on 22 sides and 5mm on 8 sides. The instrument was retrogradely inserted through the working channel of F8 semi-rigid ureteroscope, and the small site of the ureteral lumen was dilated under direct endoscopic view. After a single dilation, the balloon catheter was withdrawn, and the effect of dilation was evaluated by semi-rigid ureteroscopy to determine whether to proceed with the following procedures. The intraoperative data were recorded, including surgical method, stage of "difficult ureter" occurred, site of the small part of the ureter, related data of utilizing ureteral dilatation balloon catheter, grade of ureteral injury after dilatation (according to the 0-4 grading classification of endoscopic ureteral injuries), total operation time, balloon catheter-related adverse events, stone-free rate, and time of removing ureteral stents.Results:Among the 30 sides, 29 (96.7%) had difficulty in the stage of ureteroscope insertion, and 1(3.3%) had difficulty in the stage of UAS insertion. A total of 37 small sites of ureter were involved, including 18 in the intramural segment, 10 in the lower part, 2 in the middle part, and 7 in the upper part. Each site was dilated once with a median time of 3 (0.5, 5.0) minutes and a median maximum balloon pressure of 1 215.9(1 215.9, 1 443.9)kPa[12.0(12.0, 14.3)atm]. There were 28 sites of grade Ⅰ injury, 8 sites of grade Ⅱinjury, and 1 site of grade Ⅲinjury. The total duration of unilateral procedure was (73.4±30.3) min. Ureteroscope or UAS insertion was successful in 28 sides(93.3%) after balloon dilation, and failed in 2 sides(6.7%), both of which were in the stage of inserting ureteroscope and ureteral stent was indwelled for the second-stage procedures. On the first day after surgery, the hemoglobin level was (134.1±12.9)g/L, which was significantly different from the preoperative parameters ( P<0.01), and serum creatinine level was (86.7±23.2)μmol/L, which showed no significant difference from the preoperative one ( P=0.263). The primary stone-free rate was 92.9% (26/28), and the total postoperative complication rate was 13.3% (4/30), including 3 of grade Ⅰ (lateral lower abdominal pain requiring additional analgesic drugs) and 1 of grade Ⅱ (postoperative hematuria requiring intravenous hemostatic drugs). Follow-up was conducted for 3 months. All of the 28 successful sides had their ureteral stents removed before the last follow-up, and the time of removal was (36.9±11.5) days. No hydronephrosis was found in the ipsilateral kidney by ultrasound 3 months after operation. Conclusions:Balloon dilation technique showed good efficacy and safety in the treatment of "difficult ureter" during ureteroscopic lithotripsy.

Objective:To summarize the clinical characteristics and therapeutic efficacy of central nervous system (CNS) aspergillosis.Methods:The clinical manifestations, laboratory examination, neuroimaging features, treatment and prognosis of 37 cases of CNS aspergillosis diagnosed and treated in the First Medical Center of People′s Liberation Army General Hospital from January 2000 to January 2021 were retrospectively analyzed. According to the correlation between intracranial lesions and paranasal sinus lesions, they were divided into two groups: rhino-cerebral aspergillosis (RA, n=21) group and cerebral aspergillosis (CA, n=16) group. Results:Only 16.2% (6/37) of CNS aspergillosis patients had a clear background of immunosuppression, but 35.1% (13/37) were complicated with diabetes. The most common clinical manifestations were headache (73.0%, 27/37), cranial nerve involvement (59.5%, 22/37) and fever (37.8%, 14/37). Cerebrospinal fluid characteristics included increased pressure (53.8%, 14/26), increased white blood cell count (46.7%, 14/30), decreased glucose (30.0%, 9/30), increased protein (70.0%, 21/30), and high positive results of the metagenomic next-generation sequencing (mNGS) of pathogenic microorganism (7/10). Cranial magnetic resonance imaging showed that commonly involved sites were sinus, orbital apex, posterior orbit, cavernous sinus (43.2%, 16/37) and cerebral lobes (27.0%, 10/37). Treatment options included antifungal drugs alone (64.9%, 24/37), combination of drugs and surgery (27.0%, 10/37) and surgery alone (8.1%, 3/37). Compared with the CA group, RA group had fewer males [47.6% (10/21) vs 14/16, χ2=6.34, P=0.012] and older age [(54.2±19.4) years vs (38.4±18.4) years, t=2.50, P=0.017], and was more prone to headache [85.7% (18/21) vs 9/16, χ2=4.00, P=0.046) and cranial nerve involvement [81.0% (17/21) vs 5/16, χ 2=9.31, P=0.006]. The misdiagnosis rate of these patients in the early stage was 73.0% (27/37). A total of 29 patients (85.3%, 29/34) were treated with voriconazole successively, and the course of treatment was 3.0 (0.5, 10.4) months. Compared with salvage therapy, the mortality of primary therapy was lower (4/17 vs 9/12, χ2=7.54, P=0.006). All patients were followed up to December 2021, and 17 patients died, with a mortality rate of 45.9% (17/37). Conclusions:CNS aspergillosis may have no definite immunosuppressive background. Some of CNS aspergillosis patients are complicated with diabetes, and the clinical manifestations of the disease lack specificity, with high misdiagnosis rate in the early stage, no inflammatory changes in cerebrospinal fluid, and high positive rate of mNGS for pathogenic microorganism. Early and long-term application of voriconazole can significantly reduce the mortality rate.

Objective:To investigate clinical efficacy and safety of venetoclax (VEN)-based regimens in the treatment of acute myeloid leukemia (AML).Methods:The clinical data of 41 AML patients treated with venetoclax-based regimens from January 2021 to December 2021 in Ruijin Hospital North of Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The treatment regimens included VEN+demethylating drugs ± gene mutation inhibitors or VEN+chemotherapy with a median number of 2 courses (1- 5 courses).Results:The median age of all patients was 60 years (18-73 years), and there were 24 males and 17 females. After 1 course of VEN-based therapy, 22 (53.7%) patients achieved complete remission (CR) or morphological complete remission without complete blood count recovery (CRi), including 5 patients achieving minimal residual disease (MRD) negative. After 2 courses of treatment, of 17 patients available for efficacy evaluation, 7 patients achieved MRD negative. Among 20 relapsed/refractory AML patients, 9 cases achieved CR/CRi after 1 course of treatment, of which 1 patient had MRD negative. Among 21 patients initially treated and re-treated, 13 cases achieved CR/CRi and 1 case achieved partial remission after 1 course of treatment, of which 4 cases had MRD negative.Conclusions:VEN-based treatment regimens for AML have a high remission rate and tolerable adverse effects.