Objective To explore the clinical value of laparoscopic radical cystectomy based on fascia anatomy for bladder cancer treatment.Methods The clinical data of 51 patients with bladder cancer who underwent 3D laparoscopic radical cystectomy during Jan.2015 and Jun.2022 were retrospectively analyzed.The surgery was performed based on membrane anatomy technology along four longitudinal and two transverse planes to complete the radical cystectomy.The pelvic plexus was preserved for patients with normal preoperative sexual function.Results All surgeries were completed without conversion to open operation.The mean operation time was(502.52±108.99)min,mean intraoperative blood loss was(275.96±155.18)mL,mean postoperative drainage time was(4.14±2.41)d,and the mean postoperative hospital stay was(16.37±4.85)d.The mean number of lymph nodes removed was(17.98±11.48).The mean postoperative follow-up was(30.27±19.39)months.At the last follow-up,no Clavien ≥grade 3 complications were observed.The estimated overall survival(OS),tumor-specific survival(TSS),and recurrence-free survival(RFS)were 82.4％,92.2％,and 88.2％,respectively.The lymph node positive patients had shorter OS and RFS(60.0％,60.0％)than the lymph node negative patients(84.8％,91.3％).Among the 19 male patients who underwent radical cystectomy with pre-exposure and preservation of pelvic plexus,daytime and nocturnal continence rate were 83.3％and 72.2％,respectively,and 17 patients recovered potency within 6 months postoperatively.Conclusion Laparoscopic radical cystectomy based on fascia anatomy is safe and effective in laparoscopic radical cystectomy,with standardized surgical procedure,satisfactory oncological outcomes,little hemorrhage,few complications and fast recovery.

Objective:To investigate the impacts of fatty acid binding protein 4(FABP4)silencing on endoplasmic reticulum stress(ERS)and insulin resistance(IR)in gestational diabetes mellitus(GDM)rats by regulating protein kinase R-like endoplasmic reticulum kinase(PERK)/eukaryotic initiation factor 2α(eIF2α)/transcription factor 4(ATF4)/C/EBP homologous protein(CHOP)signaling pathway.Methods:GDM rat model was established by intraperitoneal injection of streptozotocin(STZ).Rats were injected with FABP4 siRNA plasmid(si-FABP4),negative control plasmid(NC)and PERK activator(CCT020312)via tail vein,and were randomly grouped into Normal group,GDM group,GDM+NC group,GDM+si-FABP4 group and GDM+si-FABP4+CCT020312 group.The levels of FABP4,blood lipids,inflammatory markers and oxidative stress markers in pancreatic tissue were detected,the expres-sions of PERK/eIF2α/ATF4/CHOP signaling pathway-related proteins in pancreatic tissue were detected.HTR-8/SVneo cells were divided into 5 groups:Control group,high glucose(HG)group,HG+NC group,HG+si-FABP4 group,HG+si-FABP4+CCT020312 group.After 24 h,the expressions of FABP4 and PERK/eIF2α/ATF4/CHOP signaling pathway related proteins were detected.Results:Compared with Normal group,the level of FABP4 in the serum and pancreatic tissue of the GDM group were obviously up-regu-lated(P<0.05).FABP4 silencing obviously reduced FBG and IR,decreased the levels of blood lipids,CRP,TNF-α,IL-6 and MDA,and increased the levels of SOD and CAT(P<0.05).Furthermore,FABP4 silencing attenuated pancreatic and placental tissue damages.After CCT020312 up-regulated the phosphorylation levels of PERK and eIF2α and the protein expressions of ATF4 and CHOP,the inhibitory effects of FABP4 silencing on IR,inflammation,oxidative stress,and pancreatic and placental damages in GDM rats were reversed(P<0.05).FABP4 was up-regulated in HTR-8/SVneo cells induced by HG,and silencing FABP4 inhibited the protein ex-pression of the PERK/eIF2α/ATF4/CHOP pathway,while CCT020312 reversed this change(P<0.05).Conclusion:FABP4 silencing improves IR and ERS in GDM rats by inhibiting inflammation and oxidative stress,and the mechanism is related to the inhibition of PERK/eIF2α/ATF4/CHOP signaling pathway.

Objective:To investigate the efficacy and safety of anlotinib combined with whole brain radiation therapy in the treatment of driver gene mutation-negative non-small cell lung cancer (NSCLC) patients with multiple brain metastases.Methods:Forty-two driver gene mutation-negative NSCLC patients with multiple brain metastases who were admitted to Shaoxing People's Hospital from March 2018 to March 2022 were included. Among them, 21 patients in the anlotinib combined with whole brain radiation therapy group were enrolled from a prospective single-arm study (clinical trial registration number: ChiCTR1900027769), and the patients in the whole brain radiation therapy-alone group were enrolled from a concurrent retrospective study, and after 1∶1 propensity score matching, a total of 21 patients were finally included. The intracranial objective response rate (iORR), intracranial disease control rate (iDCR), intracranial progression-free survival (iPFS), overall survival (OS), and adverse events were compared between the two groups.Results:Among 21 patients in the arotinib combined with whole brain radiation therapy group, there were 1 case (4.8%) of complete remission (CR), 13 cases (61.9%) of partial remission (PR), 6 cases (28.6%) of stable disease (SD), and 1 case (4.8%) of progressive disease (PD). Among 21 patients in the whole brain radiation therapy-alone group, there were 0 case of CR, 10 cases (47.6%) of PR, 7 cases (33.3%) of SD, and 4 cases (19.0%) of PD. The iORR was 66.7% (14/21) and 47.6% (10/21) in the anlotinib combined with whole brain radiation therapy group and whole brain radiation therapy-alone group, respectively ( P = 0.212), and the iDCR was 95.2% (20/21) and 81.0% (17/21), respectively ( P = 0.343). The median iPFS time was 10.4 and 5.3 months in the anrotinib combined with whole brain radiation therapy group and the whole brain radiation therapy-alone group, respectively, and the difference in iPFS between the two groups was statistically significant ( P = 0.049); the 1-year OS rate was 50.5% and 39.5%, and the 2-year OS rate was 29.9% and 26.3%, respectively, with the median OS time of 13.4 and 6.6 months, respectively. The difference in OS between the two groups was not statistically significant ( P = 0.452). The most common treatment-related adverse effects in the anlotinib combined with whole brain radiation therapy group were loss of appetite (13/21, 61.9%), hypertension (11/21, 52.4%), fatigue (10/21, 47.6%), diarrhea (6/21, 28.6%), vomiting (6/21, 28.6%), dizziness (9/21, 42.9%), and headache (8/21, 38.1%). No ≥grade 4 adverse effects were observed, and there were no significant differences in adverse effects between the two groups (all P > 0.05). Conclusions:Anlotinib combined with whole brain radiation therapy can prolong the iPFS time of driver gene mutation-negative NSCLC patients with multiple brain metastases, and it is well-tolerated in terms of safety.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a^-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a^-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.
Animals ; Mice ; Amputation, Surgical ; Chronic Pain/pathology* ; Disease Models, Animal ; Ganglia, Spinal/pathology* ; Hyperalgesia/etiology* ; Ion Channels/metabolism* ; Macrophages ; Neuroma/pathology*

Objective:To investigate the effectiveness and safety of fully-covered self-expandable metal stent (FCSEMS) with plastic stent over the treatment of post liver transplantation anastomotic biliary stricture (AS).Methods:The clinical data of AS patients after liver transplantation admitted to the First Affiliated Hospital of Sun Yat-sen University from January 2014 to April 2018 was collected for the retrospective study. According to different implanted stents, patients were divided into FCSEMS group and plastic stent group. The general information of the two groups of patients, surgical success rate, postoperative complications, the number of endoscopic retrograde cholangiopancreatography (ERCP), the number of indwelling stents and other indicators were compared and analyzed.Results:A total of 54 patients were enrolled, including 41 males and 13 females, with a median age of 48 (34-65) years. A total of 23 cases were included in the FCSEMS group and 31 cases were included in the plastic stent group. The overall technical success rate of the operation was 98.3% (176/179). In the FCSEMS group, there were 21 patients recovered and 2 patients were relieved; in the plastic stent group, 29 patients were recovered, 1 case was relieved, and 1 case failed. There were no statistically significant differences in the efficacy and complication rate between the two groups (all P>0.05). The median stent indwelling time, ERCP times, and the number of indwelling stents in the FCSEMS group were 5.9 months, 2 times, and 1, respectively, and in the plastic stent group were 9.5 months, 4 times, and 8 respectively. There were statistical differences between the two groups (all P<0.05). Conclusions:FCSEMS for treatment of AS showed less duration of stenting, numbers of stents and endoscopic treatment sessions with the similar efficacy as plastic stents. It’s indicated that it’s necessary to pay attention to the probability of stent migration and pancreatitis.

Objective: To investigate the association between the preterm birth and low birth weight and parental thalassemia. Methods: Pregnant women and their husbands receiving prenatal examination in local hospitals or maternal and child health centers in Jingxi and Debao in Guangxi from January to December 2017 were selected as study subjects. A total of 758 pregnant women with pregnancy outcomes and their husbands, who were both or alone diagnosed with thalassemia through thalassemia gene detection, were selected as case group and 758 pregnant women with pregnancy outcomes and their husbands, who were negative in thalassemia gene detection and hemoglobin electrophoresis test were selected as control groups. The case group were further divided into mother group, father group and both mother and farther group. Clinical and pregnancy outcome data of the study subjects were collected for the analysis on the association between parental thalassaemia and preterm birth or low birth weight by the independent sample t test, χ² test and Cox regression analysis. Results: The incidence of preterm birth in case group and control group was about 6.5% and 1.6% and the incidence of low birth weight in case group and control group was about 7.3% and 0.8%. After adjusting for possible confounding factors, Cox regression analysis results showed that mother suffering from thalassemia (aRR=3.45, 95%CI: 1.35-8.81, P=0.010), fathers suffering from thalassemia (aRR=4.93, 95%CI: 2.16-11.21, P<0.001) and both mother and farther suffering from thalassemia (aRR=5.13, 95%CI: 2.62-10.04, P<0.001) were associated with preterm birth. Mother suffering from thalassemia (aRR=12.98, 95%CI: 4.91-34.30, P<0.001), fathers suffering from thalassemia (aRR=9.40, 95%CI: 3.40-25.95, P<0.001) and both mother and farther suffering from thalassemia (aRR=10.74, 95%CI: 4.44-26.00, P<0.001) were associated with low birth weight. The newborn whose parent all suffered from thalassemia had higher risks for preterm birth (χ²=22.72, P<0.001)and low birth weight (χ²=34.03, P<0.001) compared with those only with mother or father suffering from thalassemia. Conclusion Parental thalassaemia, including both sides and single side, might increase the risks of preterm birth and low birth weight for newborn, and the risks might be higher in newborn with both mother and father suffering from thalassaemia.

Objective To evaluate the clinical effects of the laparoscopic Roux-en-Y gastric bypass (LRYGB) on patients with type 2 diabetes mellitus (T2DM).Methods From Dec.2013 to Dec.2015,83 cases with T2DM received LRYGB were enrolled to this study.They were divided into low body mass index group (LBMI,25≤BMI＜28),intermediate body mass index group (IBMI,28≤BMI＜32) and high body mass index group (HBMI,BMI≥33).Meanwhile,the clinical effects and side-effects were evaluated among three groups.The factors of adverse effects were evaluated by Cox multivariate analysis.Results Only one patient in HBMI was conversed to open surgery,all the others received LRYGB.The surgery time,intraoperative blood loss and complica tion were positively related to BMI,and the difference was statistically significant between the 3 groups(P＜0.05).The main side-effect of LRYGB was gastrointestinal reaction.The level of fasting blood-glucose,postprandial 2 hours blood sugar,HbA1c and cholesterol total in three groups were lower than baseline (P＜0.05),however,there was no significant difference among the three groups (P＞0.05).The rate of clinical effects in three groups was 89.5％,89.3％ and 91.7％.There was no significant difference among the three groups(P＞0.05);In Cox multivariate analysis,cholesterol total and BMI were independent prognostic indicator for LRGB adverse.Conclusions LRYGB is a safe and effective method for patients with T2DM,which can effectively improve glucose and lipid metabolism.The increased BMI can increase the incidence of LRYGB complications.Total cholesterol is an independent prognostic indicator for the adverse of LRYGB.

Objective To explore the risk factors of hidden blood loss after UKA.Methods A retrospec-tive study was conducted on 273 patients who underwent UKA from January 2015 to December 2016,including 79 males and 194 females,age between 46 to 87 years old,mean age(67.21± 8.23)years old. The clinical data were collected and the blood volume was calculated according to the Nadler formula. The Gross equation was used to calculate the blood loss and the amount of occult blood loss at 3 days after operation. The risk factors were analyzed statistically. Results The volume of hidden blood loss after operation was(75.36 ± 10.21)mL,and the volume of total blood lost after operation was(187.35± 60.31)mL.Sex,BMI and type of prosthesis were risk factors for hidden blood loss after UKA. Conclusions The volume of hidden blood loss after UKA was related to sex, BMI,and type of prosthesis. For the obese and male patients,we should actively take bleeding management and choose the type of prosthesis reasonably.

OBJECTIVE:To investigate the use of prophylactic use of antibiotics for special diagnosis and treatment in our hos-pital,and to provide reference for rational use of antibiotics. METHODS:The patients receiving special diagnosis and treatment were collected from our hospital during Jan.-Aug. 2016. The prophylactic application of antibiotics was analyzed statistically. RE-SULTS:Among 149 included patients,there were 62 cases of prophylactic use of antibiotics with utilization rate of 41.61％. Among 62 patients receiving antibiotics,5 cases were given medicine orally and others were via injection. Nine categories 18 types of antibiotics were used,involving 69 times;cephalosporin were used in 49 times(71.01％),among which top 3 types in the list of use sequence were cefodizime,cefotetan and cefazolin;prophylactic use of antibiotics was not found in angiography(including coronary artery) and stent implantation. Utilization rate of antibiotics for other diagnosis and treatment was more than 50％. The prophylactic use of antibiotics was complex in ureteroscopy and cystoscopy,shock wave lithotripsy;the selection of drug types started from the high level. There were 59 cases of single drug(95.16％)and 3 cases of two-drug(4.84％). Total of 41 cases were given medicine 0.5-2 h before surgery or at the beginning of anaesthesia (66.13％). Medication time of 18 cases was ≤24 h (29.03％);that of 11 cases was >24-48 h(17.74％). CONCLUSIONS:The prophylactic use of antibiotics is relatively standard in angiography(including coronary artery),stent implantation and implantation of peritoneal dialysis tube in our hospital. There are some problems during special diagnosis and treatment,such as the indication of drug delivery is not strict;the selection of drug types starts from the high level;medication timing is not suitable;medication course is excessively long.