OBJECTIVE To observe the efficacy and safety of camrelizumab combined with pemetrexed and nedaplatin in the treatment of epidermal growth factor receptor （EGFR） and anaplastic lymphoma kinase （ALK） wild-type advanced non-squamous non-small cell lung cancer （NSCLC）. METHODS The data of 92 patients with EGFR/ALK wild-type advanced non-squamous NSCLC patients who visited the First Affiliated Hospital of Chongqing Medical University from August 2021 to May 2023 were collected and divided into nedaplatin group （46 cases） and carboplatin group （46 cases） based on different treatment regimens. Nedaplatin group was given camrelizumab for injection+nedaplatin for injection+pemetrexed disodium for injection； carboplatin group was given camrelizumab for injection+carboplatin injection+pemetrexed disodium for injection. Both groups received treatment with 21 days as one cycle， and all patients would be treated at least two cycles. The recent efficacy and the incidence of adverse drug reactions were observed in two groups， and the factors affecting progression-free survival （PFS） of patients were analyzed. RESULTS There was no statistically significant difference in the objective response rate， disease control rate， median PFS， and the incidence of grade 3-5 treatment-related adverse event （TRAE） between the two groups （P＞0.05）. While the incidence of grade 1-2 renal and urinary system TREA， palpitations and pericardial effusion in nedaplatin group were significantly lower than carboplatin group， the incidence of nausea， vomiting and decreased appetite were significantly higher than carboplatin group （P＜0.05）. The patient’s gender， age， smoking history， Eastern United States Cancer Collaboration score， and TNM staging were not significant factors affecting patient’s PFS （P＞0.05）. CONCLUSIONS Camrelizumab combined with pemetrexed and nedaplatin has significant efficacy in the treatment of EGFR/ALK wild-type advanced non-squamous NSCLC， with good safety.

BACKGROUND:The traditional view is that proximal fibular fractures do not require fixation.Others and our research suggest that the proximal fibular structure plays an important role in the stability of the posterolateral structure of the knee joint,and its mechanism of action is worth studying. OBJECTIVE:To investigate the biomechanical effects of proximal fibular fractures on various structures of the knee joint in an extended state. METHODS:Finite element method was used to conduct simulated biomechanical experiments.A healthy young male volunteer was selected to establish a finite element model of the knee joint in an extended state using MRI and CT image data,and four proximal fibular shapes were simulated(Model A:intact,Model B:1 cm fracture below the fibular head,Model C:1 cm tip defect fracture from the proximal end of the fibula to the distal end,and Model D:2 cm bone defect from the proximal end of the fibula).A longitudinal concentrated load of 1 500 N was applied to the femoral shaft to compare and analyze the distribution and changing trend of the maximum equivalent stress and maximum first principal stress of each structure of the knee joint in an extended state under four working conditions. RESULTS AND CONCLUSION:(1)In Model A,the maximum equivalent stress in the tibial cartilage and lateral compartment of the meniscus was greater than that in the medial compartment,while the maximum first principal stress in the tibial plateau and medial compartment of the meniscus was greater than that in the lateral compartment.The maximum equivalent stress of the medial condyle of the femoral cartilage was greater than that of the lateral condyle,and the maximum first principal stress of the medial condyle of the femoral cartilage was greater than that of the medial condyle.(2)Compared to Model A,there was no significant difference in the magnitude and distribution of the maximum equivalent stress and maximum first principal stress in the cartilage and meniscus of Model C.(3)Compared to Model A,the maximum equivalent stress increase amplitude of Model B was in the order of medial tibial cartilage(14.9％),medial condyle of femoral cartilage(13.6％),and medial meniscus(6.6％).The maximum first principal stress increase amplitude was the medial meniscus(11.06％),the medial tibial cartilage(8.65％),and the medial condyle of the femoral cartilage(7.46％).The maximum equivalent stress increase amplitude of the ligament was as follows:popliteal arch ligament(33.2％)>anterior cruciate ligament(21.3％)>fibular collateral ligament(17％)>posterior cruciate ligament(14.3％)>anterior lateral collateral ligament(13.2％)>medial collateral ligament(10.1％).(4)Compared to Model A,the maximum equivalent stress increasing trend of Model D followed the medial tibial cartilage(19.5％),femoral cartilage medial condyle(17.9％),and medial meniscus(9.9％).The maximum first principal stress in sequence was the medial meniscus(14.04％),the medial tibial cartilage(13.03％),and the medial condyle of the femoral cartilage(11.37％).The increasing trend of maximum equivalent stress in ligaments was as follows:anterior cruciate ligament(25.2％)>posterior cruciate ligament(18.9％)>medial collateral ligament(18.5％)>anterior lateral collateral ligament(12.7％).(5)It is suggested that when the knee joint is extended,a 1 cm fracture below the fibular head and a 2 cm fibular tip bone defect have a significant impact on the structure of the medial ventricular cartilage,anterior cruciate ligament,and posterior lateral ligament complex.

Objective A high sodium(HS)diet is believed to affect bone metabolism processes.Clarifying its impact on osseointegration of titanium(Ti)implants holds significant implications for postoperative dietary management of implanted patients. Methods This investigation probed the impact of sodium ions(Na+)on neovascularization and osteogenesis around Ti implants in vivo,utilizing micro-computed tomography,hematoxylin and eosin staining,and immunohistochemical analyses.Concurrently,in vitro experiments assessed the effects of varied Na+concentrations and exposure durations on human umbilical vein endothelial cells(HUVECs)and MC3T3-E1 cells. Results In vivo,increased dietary sodium(0.8%-6.0%)led to a substantial decline in CD34 positive HUVECs and new bone formation around Ti implants,alongside an increase in inflammatory cells.In vitro,an increase in Na+concentration(140-150 mmol/L)adversely affected the proliferation,angiogenesis,and migration of HUVECs,especially with prolonged exposure.While MC3T3-E1 cells initially exhibited less susceptibility to high Na+concentrations compared to HUVECs during short-term exposure,prolonged exposure to a HS environment progressively diminished their proliferation,differentiation,and osteogenic capabilities. Conclusion These findings suggest that HS diet had a negative effect on the early osseointegration of Ti implants by interfering with the process of postoperative vascularized bone regeneration.

Objective:To investigate the therapeutic effect of dorsal skin-tightening technique on the correction of mild penile curvature in children with hypospadias.Methods:The clinical characteristics of hypospadias patients (95 cases) with mild penile curvature (<30°) after degloving penis during operation in our hospital from Jan 2017 to Sep 2020 were analyzed retrospectively. Group A: A new technique, reconstructing penile pubic angle at 12 o'clock position of penile dorsal side after degloving and suturing forskin outer and inner plate with tension at 12 o'clock position, was performed in dorsal skin-tightening group (43 cases). Gtoup B: while in dorsal midline tunica albuginea plication group (52 cases), Buck fascia was incised on dorsal midline area, following by tunica albuginea plication with one or two stitches. The patients in Group A were 0.4 to 1.5 years old, and the median age was 1.1 years, urethral orifice were located on distal shaft in 36 cases, proximal in 7 cases.The patients in Group B were 0.5 to 2.6 years old, and the median age was 1.5 years, urethral orifice were located on distal shaft in 41 cases, proximal in 11 cases. The penile ventral curvature degree was recorded during regular follow-up (postoperative 6 and 12 months), as well as postoperative complications.Results:Artificial erection test showed penile curvature was corrected during surgery by measuring with protractor. There was no chordee by measuring with the side photos in all patients during an average of 1.6 years follow-ups. There were 4 case of urethral fistula in Group B and 3 cases in Group A. No cases of urethrostenosis, diverticulum or concealed penis was recorded. The difference of postoperative complications had no statistical significance.Conclusion:Hypospadias with mild penile curvature could be effectively corrected by dorsal skin-tightening technique, which showed a good result of early follow-up.

Objective To investigate the effect of a modified preputial flap urethroplasty in twostage treatment of severe hypospadias.Methods The clinical characteristics of the severe hypospadias patients (41 cases) who underwent the staged urethroplasty by using the procedure of preset urethral plate with preputial flap from January 2015 to December 2016 were analyzed retrospectively.We used a modified method (modified group,23 cases):Form the distal urethra with the transected distal urethral plate by using tubularize incised plate (TIP) procedure during the first stage operation,after completely straightened the penis,urethral plate was preseted with transverse preputial flap at the penis shaft.While in the traditional group (18 cases),urethral plate was preseted with preputial flap by using Bracka procedure after transecting urethral plate.The corresponding missing part of urethra underwent urethroplasty at the second stage operation six months later.The patients in the modified group were 9 to 18 months old,and the median age was 13 months;meatus were located at the penis shaft in 10 cases,scrotum in 12 cases,perineum in 1 case.The patients in the traditional group were 9 to 18 months old,and the median age was 13 months;meatus were located at the penis shaft in 6 cases,scrotum in 10 cases,and perineum in 2 cases.There was no statistic difference in age and meatus position between the two groups.Results During the first stage operation,distal urethra was repaired by 13-19 mm,with an average of (14.5 ± 1.3) mm,and the proximal urethra was repaired by 0-6 mm,with an average of (3.1 ± 2.4) mm at the modified group.While at the traditional group,the length of proximal urethra was repaired of 0-9 mm,with an average of (5.6:±:2.9) mm.The urethral length required for reconstruction was measured during the second stage operation,with an average of (26.3:t:4.4) mm in the modified group and (40.5 ± 3.3) mm in the traditional group (P ＜ 0.05).There were 3 case of urethral stricture after removed the catheter,with 2 cases in the modified group and 1 case in the traditional group.Postoperative follow-up was 2 to 3 years,with an average of 2.4 years.There were 3 cases (3/23,13.0％) of urethral fistula in the modified group and 3 cases (3/18,16.7％) in the traditional group.Ascended testis occured in 2 patients in the traditional group after operation.No case of urethrostenosis,diverticulum,chordee or concealed pennis was recorded.There was no significant difference in postoperative complications between the two groups (P ＞ 0.05).Conclusions The modified staged preputial flap method shorten the new forming urethra by making full use of its own materials at the second stage operation,which was helpful to reduce complications.

Objective To review the clinical characteristics of urethral prolapse in female children and summarize our experience of treatment.Methods A retrospective analysis of the clinical characteristics of 102 patients with urethral prolapse from January 2007 to December 2017 was conducted at The Children's Hospital of Zhejiang University School of Medicine.The age of the patients ranged from 8-156 months with an median of 80 months.The presenting symptoms in the 102 girls were:bleeding in 57 patients (55.9％),mass in 31 patients (30.4％),and dysuria/urinary frequency,urgent and pain in 14 patients (13.4％).In all,58 patients were managed conservatively with Sitz baths as their masses were small,39 underwent prolapse reduction under topical anesthesia and Sitz baths because their mass were large,and 5 patients were treated by excision of the prolapsed urethral mucosa with four-quadrant excisional technique because thrombosed urethral prolapse at first visit.Results A total of 89 patients were cured after conservative treatment (87.3％),8 patients were converted to surgical treatment because frequent recurrence with conservative treatment.No urethral stricture,active hemorrhage and recurrent were found in 13 patients after operation.Conclusions The most common clinical manifestations of urethral prolapse are urethral mass and bleeding.Most patients can be cured by conservative treatment.The patients whose symptoms were severe or suffered from frequent recurrence of urethral prolapse should be managed with surgical excision.

Objective To investigate the effect of replacing a smaller-size catheter after tubularized incised plate (TIP) urethroplasty on postoperative urethral complications.Methods The data of 116 hypospadias patients underwent TIP urethroplasty performed by the same urologist in our hospital from January 2014 to December 2017 were retrospectively analyzed.The age of patients ranged from 0.5-15.4 years,with the median age of 1.5 years.Meatal location was distal in 47 (39.5％),midshaft in 62 (52.1％) and proximal in 10(8.4％) patients.Unhealthy urethral plate occurred in 49 (42.2％) patients.F8 catheter was used for urethroplasty in 92 (79.3 ％) patients,F10 in 17 (14.7％),and F12 in 7 (6.0％).According to the pattern of urinary diversion,patients were divided into two groups.Conventional catheter group in 56 patients (group A):the catheter was chosen in as large size as possible for urethroplasty without tension.Replace a smaller-size catheter group in 60 patients (group B):replace a smaller-size catheter after urethroplasty on the basis of group A.There were no statistically significant differences in age,meatal location and catheter size between the two groups (P ＞ 0.05).Results The mean follow up was 23 months (range 6-66 months).There were 73(62.9％) cases of orifice overflow during indwelling catheterization.There were 5 (4.3％) patients needed further reoperation result from postoperative urethral complications,including 4 cases of fistula and 1 case of meatal stenosis.The process of replacing a smaller-size catheter after urethroplasty in group B was simple and without adverse reactions.There were 15 (26.8％) cases of orifice overflow in group A and 58 (96.7％) in group B.There were statistically significant differences in orifice overflow between the two groups (P ＜ 0.05).There were 5 (8.9％) cases of postoperative urethral complications in group A and 0 case in group B.There were statistically significant differences in postoperative urethral complications (P ＜ 0.05).Conclusions The process of replacing a smaller-size catheter after TIP urethroplasty in was simple and subsequently contributed to less postoperative urethral complications.The results of replacing a smaller-size catheter after TIP urethroplasty were superior to that of no replacing conventionally.

Objective To investigate the application of pedicled tunica vaginalis flap cover new urethra in redo and second-stage hypospadias repair.Methods Retrospective analysis was performed in 45 redo hypospadias repair cases,aged from 1 year 3 months to 9 years 4 months (median 5 years 3month).All patients were divided into urethral dehiscence after hypospadias repair (group A) and the second stage surgery of two-stage hypospadias repair (group B) based on medical history.According to the site of dehiscence,the group A were further divided into midshaft urethral dehiscence (A1) and glans and distal urethral dehiscence with urethral opening located on midshaft (A2).After new urethra was completed,the appropriate size of the pedicledtunica vaginalis flap was transferred to cover the new urethra.Results There was no scrotal hematoma occurred in all 45 cases,and somecomplications occurred,including scrotal swelling in 1 case,high-riding testicle in 2 cases,penile clockwise torsion in 1 case,urethrocutaneous fistula in 6 cases.All the 45 cases were followed up for 1 to 4 years,with mean of 1.8 years.One more urethrocutaneous fistula occurred in group A2 and 1 more urethrocutaneous fistula with urethral stricture occurred in group B.There was no penile curvature and urethral diverticulum occurred in all cases.Conclusions Pedicled tunica vaginalis flap could be used as waterproofing layer to cover new urethra in redo hypospadias repair and presented a low incidence rate of postoperative complications.

Objective To investigate the proper procedure for repairing different urethrocutaneous fistulas after primary urethroplasty for hypospadias.Method There were 101 cases,whose age ranged from 27 months to 171 months (mean 61 months),underwent urethrocutaneous fistula repairing secondary to the primary hypospadiasis urethroplasty from January 2010 to December 2015.The methods of the repairing were chosen mainly on the site and the size of the fistula,which included three types.The coronal fistula with a thin band of tissue stretching between the glans wings was classified as type Ⅰ (n =24).For the rest of the small fistulas at penis coronal ditch and penis body,the small fistula (diameter ＜ 3 mm) was classified as type Ⅱ (n =57) and the large fistula (diameter ≥3 mm) was classified as type Ⅲ(n =30).The urethroplasty was performed in the type Ⅰ cases.The ligation and transfixion was performed in type lⅡ cases.And the tension free repairing with continuous suture was performed in type Ⅲ cases.De-epithelization dartos fascia flap or tunica vaginalis flap covering was performed in all cases.After removing the catheter,all cases were followed-up at least 1 year.The successive operation was termed as no complication,such as urethral stricture,urethral diverticulum and urethrocutaneous fistula.Result Totally 111 fistulas were repaired by the methods described above.The mean followed-up duration was 32 months (ranging 12-48months).Total recurrence of fistula was 11.7％ (13/111) in different type fistulas,including 16.7％(4/24) in type Ⅰ,3.5％ (2/57) in type Ⅱ and 23.3％ (7/30) in type 1Ⅲ.Conclusions Different classification and treatment of urethrocutaneous fistula after urethroplasty by the site and size of fistula can improve the outcome of the operation.It is necessary to cover the tissue tightly to a new urethra during the operation.

Objective To evaluate the effect of sevoflurane preconditioning on the expression of heat shock protein 70 (HSP70) during renal ischemia-reperfusion in rats.Methods Twenty-four pathogen-free healthy adult male Sprague-Dawley rats,weighing 250-300 g,aged 2-3 months,were divided into 3 groups (n=8 each) using a random number table:sham operation group (group S),renal I/R group (group I/R) and sevoflurane preconditioning group (group SP).The animals were anesthetized with 2％ pentobarbital sodium 50 mg/kg.After the right kidney was removed,the left renal artery was clamped for 45 min followed by 2 h reperfusion to establish the model of renal I/R injury.In group SP,2.2％ sevoflurane was inhaled for 1 h followed by 10-min washout before the model was established.The animals were sacrificed at the end of rcpcrfusion,and kidneys were then removed for determination of the expression of HSP70 (by immunohistochemistry) and malondialdehyde (MDA) content in renal tissues (by thiobarbituric acid colorimetric method).Results Compared with group S,the expression of HSP70 in renal tissues was significantly up-regulated,and the MDA content in renal tissues was increased in t/R and SP groups (P＜0.05).Compared with group I/R,the expression of HSP70 in renal tissues was significantly up-regulated,and the MDA content in renal tissues was decreased in group SP (P＜0.05).Conclusion The mechanism by which sevoflurane preconditioning reduces renal I/R injury is related to up-regulation of HSP70 expression in rats.