【Objective】 To explore the feasibility of en-bloc resection of bladder tumors by flexible cystoscope combined with laparoscopic instruments through urethra and to provide reference for the clinical application of this technique. 【Methods】 Self-designed and processed transurethral single-hole PORT and Olympus electronic cystoscope were used as observation mirror; Φ1.8 mm soft grasper, tissue scissors, electric hook, and ultrasonic scalpel were used as instruments; the porcine bladder was used as a model.The PORT was placed through the urethra, and the cystoscope was inserted to observe the inner wall of the bladder and the condition of the mucosa.After the lesion site was identified in the bladder cavity, the soft grasper was inserted to pull the mucosa to be removed, which was then fixed with tension at the target position to maintain a satisfactory feild of view.The surgeon held the cystoscope in the left hand, and operated the laparoscopic instruments into the bladder cavity through the PORT with the right hand.Observing with the cystoscope and lifting and pulling the mucosa with the grasper, the surgeon simulated the cutting and pushing actions to realize the en-bloc resection of the lesioned mucosa. 【Results】 The mucosa at 4 different locations were successfully resected on 2 in vitro porcine bladder models. 【Conclusion】 The in vitro experiments show that the combination of flexible electronic cystoscope and laparoscopic instruments achieves synergistic effects in en-bloc resection of bladder tumor by transurethral single-hole laparoscope without additional iatrogenic bladder injury caused by percutaneous bladder incision.This method is feasible in the treatment of bladder tumors, and has the potential of clinical application after further optimization.

Objective To investigate the impact of esketamine hydrochloride in combination with ultrasound-guided transverse thoracic muscle plane block on stress response and inflammatory levels in patients undergoing cardiac valve replacement under general anesthesia.Methods A total of 120 patients who underwent elective extra-corporeal circulation-supported median open heart valve replacement were selected and randomly assigned into four groups using the random number table method:general anesthesia alone(Group G),general anesthesia with intrave-nous administration of esketamine(Group E),general anesthesia with transverse thoracic plane block(Group T),and esketamine combined with transverse thoracic muscle plane block(Group ET);each group consisted of 30 cases.Patients in group E and group ET received a continuous infusion of esketamine hydrochloride injection at a rate of 0.2 mg/kg-1?h-1 until the completion of the surgical procedure,while patients in group G and group T received an equivalent volume of saline solution until the completion of the surgical procedure.After the induction of general anesthesia,patients in group T and group ET underwent ultrasound-guided bilateral transverse thoracic muscle plane block,while patients in group G and group E did not receive any specific intervention.All four groups received identical protocols for anesthesia induction and maintenance,with self-controlled intravenous analgesic pumps administered to all patients postoperatively.The following time points were recorded:1 day prior to surgery(T0),pre-induction of anesthesia(T1),1 minute post-tracheal intubation(T2),1 minute post-median sternotomy(T3),1 minute prior to initiation of cardiopulmonary circulation(T4),1 minute after cessation of cardiopulmonary circula-tion(T5),1 minute after completion of surgery(T6),1 day post-surgery(T7),2 days post-surgery(T8),and 3 days post-surgery(T9).Mean Arterial Pressure(MAP)and Heart Rate(HR)were continuously monitored from T1 to T6.The levels of blood glucose and lactate were measured and recorded at T1,T4 to T6.The levels of White Blood Cells(WBC)and C-Reactive Protein(CRP)were assessed at T0,as well as at T7 to T9.The occurrence of postoperative adverse reactions was documented in all four groups.Results(1)Comparison of hemodynamics among the four groups:Compared with group G,there was a significant decrease in MAP and HR at T3 in group T(P<0.05).At the T5 time point,MAP was lower in group ET compared to group E,while HR was higher in group ET compared to group T(P<0.05).(2)The lactate and blood glucose levels of the four patient groups after extracorporeal circulation transfer were higher than those at the T1 time point(P<0.05).Patients in group E had lower lactate values at the T5 time point and lower blood glucose values at the T6 time point compared to group G(P<0.05).Additionally,patients in group E exhibited lower lactate and blood glucose values at both the T5 and T6 time points compared to those in group T(P<0.05).(3)Compared to T0,the levels of white blood cells(WBC)and C-reactive protein(CRP)were increased in all four groups after surgery(P<0.05).At the T7 time point,the WBC levels in group E and group T were significantly lower than those in group G(P<0.05).Furthermore,compared to group E and group T,the level of WBC in group ET was significantly lower at T7,while the level of CRP was significantly lower at T8(P<0.05).(4)There were no significant differences observed in postoperative adverse reactions among the four groups(P>0.05).Conclusion Combining low-dose esketamine hydrochloride with transverse thoracic muscle plane block under general anesthesia during open heart valve replacement surgery can effectively stabilize the patient's hemodynamics,mitigate perioperative stress response and postoperative inflammation levels,thereby demonstrating significant clini-cal utility.

Objective To investigate the efficacy and safety of cryoablation combined with Camrelizumab monoclonal antibody in the treatment of hepatocellular carcinoma(HCC).Methods A total of 103 HCC patients who were admitted to our hospital from June 2020 to June 2023 were enrolled and randomly divided into combined treatment group with 53 patients and control group with 50 patients.The patients in the control group received percutaneous argon-helium cryoablation,and those in the combined treatment group received percutaneous argon-helium cryoablation combined with Camrelizumab monoclonal antibody.The two groups were compared in terms of short-term response,changes in T lymphocyte subsets after treatment,changes in liver function and alpha-fetoprotein(AFP)after treatment,and progression-free survival and overall survival during follow-up.The t-test was used for comparison of normally distributed continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to plot survival curves,and the log-rank test was used for comparison of survival time between the two groups.Results The combined treatment group had significantly higher overall response rate and disease control rate than the control group(χ2=4.156 and 4.348,P=0.042 and 0.037).After treatment,the combined treatment group had significant increases in the percentages of CD3+and CD4+T lymphocytes and CD4+/CD8+ratio(P＜0.05)and a significant reduction in the percentage of CD8+T lymphocytes(P＜0.05),while the control group had no significant changes in T lymphocyte subsets after treatment(P＞0.05),and compared with the control group after treatment,the combined treatment group had significantly higher percentages of CD3+and CD4+T lymphocytes and CD4+/CD8+ratio(all P＜0.05)and a significantly lower percentage of CD8+T lymphocytes(P＜0.05).After treatment,both groups had significant reductions in the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and AFP(all P＜0.05)and a significant increase in the level of albumin(Alb)(P＞0.05),and compared with the control group after treatment,the combined treatment group had significantly lower levels of ALT,AST,and AFP(all P＜0.05)and a significantly higher level of Alb(P＜0.05).There were no significant differences in the incidence rates of grade Ⅲ—Ⅳ(moderate to severe)adverse reactions between the two groups(P＞0.05).Compared with the control group,the combined treatment group had significantly better median progression-free survival(21.32 months vs 15.31 months,χ2=4.689,P=0.030)and median overall survival(28.36 months vs 20.75 months,χ2=5.030,P=0.025).Conclusion Argon-helium cryoablation combined with Camrelizumab monoclonal antibody can effectively improve short-term response,enhance immune function,and prolong survival time,with a favorable safety profile.

In recent years, artificial intelligence (AI) has been widely applied in the field of drug discovery and development.In particular, natural language processing technology has been significantly improved after the emergence of the pre-training model.On this basis, the introduction of graph neural network has also made drug development more accurate and efficient.In order to help drug developers more systematically and comprehensively understand the application of artificial intelligence in drug discovery, this article introduces cutting-edge algorithms in AI, and elaborates on the various applications of AI in drug development, including drug small molecule design, virtual screening, drug repurposing, and drug property prediction, finally discusses the opportunities and challenges of AI in future drug development.

Objective:To investigate the feasibility and adverse reactions of simultaneous integrated boost (SIB) in volumetric modulated arc therapy (VMAT) for early breast cancer after breast-conserving surgery.Methods:A total of 67 patients with early breast cancer after breast-conserving surgery at Zhongshan People's Hospital from September 2019 to May 2021 were enrolled. All patients received VMAT-SIB to the whole breast and tumor bed. The total breast dose and tumor bed dose were 40.5Gy/15 times every 3 weeks and 48 Gy/15 every 3 weeks respectively. The exposure dose of organs at risk and acute adverse reactions of radiotherapy were evaluated.Results:The average doses of planning target volume of the whole brease (PTV WB) and planning target volume of the boost(PTV BOOST) were (42.0±2.1) Gy and (49.9±0.8) Gy, respectively. The V 95% and V 105% of PTV WB and PTV BOOST were (98.8±1.2)% and (31.4±11.3)%, (99.8±0.6)% and (22.9±10.2)%, respectively. The V 5Gy, V 20Gy, V 30Gy and mean dose (D mean) of ipsilateral lung were (52.4±12.0)%, (15.3±4.5)%, (6.7±2.2)% and (11.0±2.4) Gy respectively. The V 18Gy, V 40Gy and D mean of heart were 3.80% (0.48%,9.60%), 0 (0,0.16%) and (6.7±2.1) Gy respectively. At the end of radiotherapy, 19 patients (29%) of all 67 patients had no acute skin toxicity, 41 patients (61%) showed radiation erythema, 5 patients (7%) had radioactive dry peeling and 2 patients (3%) had wet peeling mainly located in the nipple, areola area and breast folds. None of the patients had grade 3-4 acute skin reactions. Breast swelling and breast pain were found respectively in 9 patients (13%) and 7 patients (10%). No local recurrence or distant metastases were observed during the follow-up period. The 2-year disease-free survival rate was 100%. Conclusions:VMAT combined with SIB is feasible in the treatment of early breast cancer. The adverse reactions of radiotherapy are mild and well tolerated.

In order to improve the success rate of supraclavicular deep venous catheterization and reduce mechanical complications, we present an auxillary maneuver in regard to supraclavicular subclavian catheterization basing on the relatively fixed anatomy of subclavian vein and its adjacent surroundings, furthermore, we revised the standardized procedure of supraclavicular subclavian catheterization. The maneuver is summarized in the shape of verses (verses: thumb navigation is well designed according to anatomy. Needle penetrated into vein should be parallel to coronal plane. Fine needle in position should be immobilized. Is it difficult for parallel puncture? Pressure determination is required when needle is in place. It is critical to distinguish which vessel has been inserted. Guidewire is advanced smoothly. Check blood return after expansion of skin and catheterization.). For teaching convenience, verses are considered to be more concise and memorable, as well as applicable to clinical practice, in order to provide some help for clinical teaching.

To investigate the effects of ultrasound combined with microbubbles on intracellular Ca2+ homeostasis in carboplatin ( CBP )‐treated A549 cell and its possible mechanisms of inhibiting A549 cell line activity . Methods According to whether SonoVue was used or not ,and the different dose of CBP ,the groups A‐F were arranged as the ultrasound( US) group( group A ) ,the ultrasound combined with microbubbles ( USMB) group( group B) ,the low dose CBP ( 100 μg/ml) + US group( group C) ,the low dose CBP+USMB group( group D) ,the high dose CBP ( 200 μg/ml)+ US group ( group E) and the high dose CBP+USMB group( group F) .A549 cells were bathed and washed by a calcium‐free buffer , loaded with Ca2+ indicator fluo‐4 AM . Real‐time images were acquired using laser confocal microscopy . T he fluorescence intensity of intracellular calcium ion concentration ( [ Ca 2+ ] i ) in individual living cell was observed and the calcium overload was analyzed . Results After ultrasound irradiation ,the normalized fluorescence intensity of [ Ca2+ ] i increased rapidly ,then returned to a new homeostasis ( selected cells in groups A ,B ,E ,F ) or experienced a second calcium oscillation ( some cells in group C and D ) . All the selected cells in group B and some cells in group C and D exhibited superimposed oscillations . T he calcium overloading time in group D was longer than those of any other groups . Four cells in group A experienced delayed calcium oscillations . Compared with group A ,the selected cells in other groups exhibited a larger amplitude of calcium oscillation ( all P ＜ 0 .05 ) and the selected cells in group B and D exhibited calcium oscillation for a longer period of time( all P ＜0 .05) . Conclusions In the calcium‐free buffer ,US ,USMB , CBP+ US ,CBP + USMB are direct stimuli of calcium overload in A 549 cells . SonoVue ,CBP ,CBP +SonoVue are all synergistic stimuli of calcium overload in A 549 cells irradiated by ultrasound .US ,USMB and CBP may synergistically induce calcium release from intracellular store sites in A 549 cells . Calcium overload is a possible mechanism of ultrasound combined with microbubbles in assisting CBP chemotherapy .

Objective To investigate the effects of ultrasound combined with microbubbles on intracellular Ca2+ homeostasis in carboplatin ( CBP )-treated A549 cell and its possible mechanisms of inhibiting A549 cell line activity . Methods According to whether SonoVue was used or not ,and the different dose of CBP ,the groups A-F were arranged as the ultrasound(US) group(group A) ,the ultrasound combined with microbubbles ( USMB) group( group B) ,the low dose CBP ( 100 μg/ml) + US group( group C) ,the low dose CBP+USMB group( group D) ,the high dose CBP ( 200 μg/ml)+ US group ( group E) and the high dose CBP+USMB group( group F) .A549 cells were bathed and washed by a calcium-free buffer , loaded with Ca2+ indicator fluo-4 AM . Real-time images were acquired using laser confocal microscopy .The fluorescence intensity of intracellular calcium ion concentration ([Ca2+ ]i) in individual living cell was observed and the calcium overload was analyzed . Results After ultrasound irradiation ,the normalized fluorescence intensity of [Ca2+ ]i increased rapidly ,then returned to a new homeostasis (selected cells in groups A ,B ,E ,F) or experienced a second calcium oscillation ( some cells in group C and D) . All the selected cells in group B and some cells in group C and D exhibited superimposed oscillations . The calcium overloading time in group D was longer than those of any other groups . Four cells in group A experienced delayed calcium oscillations . Compared with group A ,the selected cells in other groups exhibited a larger amplitude of calcium oscillation( all P < 0 .05) and the selected cells in group B and D exhibited calcium oscillation for a longer period of time( all P <0 .05) . Conclusions In the calcium-free buffer ,US ,USMB , CBP+ US ,CBP + USMB are direct stimuli of calcium overload in A 549 cells . SonoVue ,CBP ,CBP +SonoVue are all synergistic stimuli of calcium overload in A 549 cells irradiated by ultrasound .US ,USMB and CBP may synergistically induce calcium release from intracellular store sites in A 549 cells . Calcium overload is a possible mechanism of ultrasound combined with microbubbles in assisting CBP chemotherapy .

The inhibitory effect of NACOS on dyslipidemia and potential molecular mechanisms by in vitro and in vivo experiments were investigated. For in vitro study, four experimental groups were designed by using HepG2 cells, including the control group, palmitic acid (PA) treatment alone group, NACOS treatment alone group and NACOS + PA treatment group. For in vivo study, male C57BL/6 mice were divided into four groups (n=5) at random including the normal control group (NCD), high fat diet (HFD) group, NACOS treatment alone group, NACOS+HFD group, which were treated for 20 weeks. The used methods in this study were as follows: the observation of lipid droplet deposition in HepG2 cells by oil red O staining, the detection of mRNA levels of lipid metabolism-related regulators and inflammatory cytokine by RT-PCR method, the monitoring of MAPKs and PI3K/Akt pathway activation by Western blotting method. The in vitro study shows that, NACOS had no toxicity on the viability of HepG2 cells at 25-100 μg/mL and significantly reduced the deposition of lipid droplet. Also, based on both in vitro and in vivo investigation, NACOS evidently down-regulated the expression of lipid metabolism-related regulators (PGC1α, Cox5b, Mcad) and inflammatory cytokine (IL-1β) at mRNA level (P<0.05 or 0.01), and suppressed the activation of p38, ERK1/2 and Akt in HepG2 cells and lever tissues from HFD-fed mice (P<0.05 or 0.01). Based on the above, NACOS may inhibit the oxidation of liver mitochondrial fatty acid and the lipid biosynthesis, block the inflammatory responses and prevent the HepG2 cells and C57BL/6 mice from lipidemia.

Objective To compare laparoscopic hepatectomy to open surgery in recurrent hepatolithiasis.Methods From Jan 2014 to Feb 2016,106 cases of recurrent hepatolithiasis eligible for hepatectomy were prospectively randomized into laparoscopic group (53cases) and open group (53 cases).The perioperative variables,postoperative morbidity and outcomes were analyzed and compared between the 2 groups.Results The statistical results show that the laparoscopic group and open group had similar intraoperative rate of blood loss ＞400 ml,wound infection,abdominal infection,Grade B bile leakage,score of Clavien classification system,stone clearance rate and hospitalization cost (P ＞ 0.05).The laparoscopy group had longer operation time (P ＜ 0.05),and shorter postoperative hospital stay (P ＜0.05).Binary logistic analysis showed that decreased preoperative platelet count,longer operation time,and hepatectomy in difficult places are risk factors for intraoperative blood loss ＞ 400 ml (OR ＞ 1,P ＜0.05);type of past biliary tract operation,positive bile culture during surgery and residual stones are risk factors for grade B bile leakage (OR ＞ 1,P ＜ 0.05).Conclusions Laparoscopic hepatectomy for recurrent hepatolithiasis is safe and feasible.