[Efficacy and safety analysis of venetoclax combined with hypomethylating agents for the treatment of higher-risk myelodysplastic syndromes in the real world].

Objective: To investigate the efficacy and safety of combining venetoclax (VEN) with hypomethylated drugs (HMA) in the treatment of higher-risk (IPSS-R score >3.5) myelodysplastic syndromes (MDS) . Methods: From March 2021 to December 2022, forty-five MDS patients with intermediate and high risk were treated with VEN in combination with HMAs. Clinical data were collected and analyzed retrospectively, including gender, age, MDS subtype, IPSS-R score, treatment regimen, and efficacy, etc. Kaplan-Meier method and Cox regression model were used to analyze univariate and multivariate of survival prognosis. Results: ①Forty-five patients with MDS, including ninety-one percent were classified as high or very high risk. According to the 2023 consensus proposal for revised International Working Group response criteria for higher-risk MDS, the overall response rate (ORR) was 62.2% (28/45), with the complete response rate (CR) was 33.3% (15/45). For twenty-five naïve MDS, the ORR was 68% (17/25) and the CR rate was 32% (8/25). In nonfirst-line patients, the ORR and CR were 55% (11/20) and 35% (7/20) respectively. The median cycle to best response was 1 (1-4). ②With a median followup of 189 days, the median overall survival (OS) time was 499 (95% confidence interval, 287-711) days, and most patients died from disease progression. Responders had a significantly better median OS time than nonresponders (499 days vs 228 days, P<0.001). Multifactor analysis revealed that IPSS-R score and response to treatment were independent prognostic factors for OS; the presence of SETBP1 gene mutations was associated with a longer hospital stay (51.5 days vs 27 days, P=0.017) . Conclusions: There is clinical benefit of venetoclax in combination with hypomethylated agents in patients with higher-risk MDS, but adverse events such as severe hypocytopenia during treatment should be avoided.

Interaction between handgrip strength and vitamin D deficiency on all-cause mortality in community-dwelling older adults: a prospective cohort study.

OBJECTIVE: Muscle strength decline and vitamin D deficiency are coexisting conditions associated with multiple adverse health outcomes. This prospective study aimed to investigate the multiplicative and additive interactions between handgrip strength (HS) and serum 25-hydroxyvitamin D [25(OH)D] on all-cause mortality in Chinese community-dwelling older adults. STUDY DESIGN: This is a population-based cohort study. METHODS: 2635 older adults (85.15 ± 12.01 years) were recruited from the Chinese Longitudinal Healthy Longevity Survey (2012-2018). Low HS was defined according to the Asian Working Group for Sarcopenia 2019 updated consensus (<28 kg for men and <18 kg for women). Serum 25(OH)D < 50 nmol/L were defined as vitamin D deficiency. Cox proportional hazard models were used to examine the association of HS and 25(OH)D with all-cause mortality. Socio-demographics, health status, and clinical characteristics were included as covariates. RESULTS: 1715 (65.09 %) and 1885 (71.54 %) participants had low HS and vitamin D deficiency, respectively. During a median follow-up of 3.52 years, 1107 older people died. After multivariable adjustment, both HS and 25(OH)D levels were inversely associated with all-cause mortality risk (Ps < 0.001). The hazard ratios (HRs) of low HS and vitamin D deficiency for all-cause mortality were 1.73 (95 % CI: 1.41-2.13) and 1.61 (95 % CI: 1.32-1.93), respectively. Although significant multiplicative interactions were not found, the association between low HS and all-cause mortality was attenuated in the higher 25(OH)D subgroup than in the lower 25(OH)D subgroup (stratified by 50 nmol/L). The multiple-adjusted HR of mortality for combined low HS and vitamin D deficiency was 2.18 (95 % CI: 1.73-2.56), which was higher than that for these two conditions alone. Significant additive interactions between low HS and vitamin D deficiency on mortality were observed (relative excess risk due to interaction: 0.71, 95 % CI: 0.37-1.05). CONCLUSIONS: Low HS and low 25(OH)D levels synergistically increased the risk of all-cause mortality. Our results added new insights to the priority of early detection for older adults with comorbid muscle strength decline and vitamin D deficiency.

[Clinical analysis of long-term survival and influencing factors of chimeric antigen receptor T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia].

Objective: To analyze the survival and influencing factors of chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia (R/R B-ALL) . Methods: Clinical information of patients who received CAR-T-cell therapy and achieved complete remission of R/R B-ALL between May 2015 and June 2018 at the Shaanxi Provincial People's Hospital was obtained. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and leukemia-free survival (LFS) times of patients, and Cox regression analysis was performed to analyze the prognostic factors that affect patient survival after CAR-T therapy. Results: Among the 38 patients with R/R B-ALL, 21 were men, with a median age of 25 (6-59) years and a median OS time of 18 (95% CI 3-33) months. Multivariate Cox regression analysis showed that positive MLL-AF4 fusion gene expression was an independent risk factor for OS and LFS (OS: HR=4.888, 95% CI 1.375-17.374, P=0.014; LFS: HR=6.683, 95% CI 1.815-24.608, P=0.004). Maintenance therapy was a protective factor for OS and LFS (OS: HR=0.153, 95% CI 0.054-0.432, P<0.001; LFS: HR=0.138, 95% CI 0.050-0.382, P<0.001). In patients with MRD negative conversion, LFS benefit (HR=0.209, 95% CI 0.055-0.797, P=0.022) and OS difference was statistically insignificant (P=0.111). Moreover, patients with high tumor burden were risk factors for OS and LFS at the level of 0.1 (OS: HR=2.662, 95% CI 0.987-7.184, P=0.053; LFS: HR=2.452, 95% CI 0.949-6.339, P=0.064) . Conclusion: High tumor burden and high-risk genetics may affect the long-term survival rate of patients with R/R B-ALL receiving CAR-T, and lenalidomide-based maintenance therapy may improve their prognosis.

Comparison of efficacy and safety of flexible ureteroscopy and mini-percutaneous nephrolithotomy for 2-3 cm renal calculi in women: a single-center study.

OBJECTIVE: This study aimed to compare the efficacy and safety of flexible ureteroscopic lithotripsy (FURSL) and mini-percutaneous nephrolithotomy (mPCNL) in the treatment of 2-3 cm renal calculi in women. PATIENTS AND METHODS: Clinical data of 186 patients who underwent mPCNL (n=96) and FURSL (n=90) surgery in our hospital from June 2018 to February 2023 were collected. Several parameters were assessed and compared between the two groups, including operation duration, length of hospital stay, cost of hospitalization, pain intensity measured by the visual analogue scale (VAS), patient comfort assessed using the Bruggrmann Comfort Scale (BCS), decrease in hemoglobin levels, changes in blood urea nitrogen (BUN), fluctuations in serum creatinine (Scr), hypersensitive C-reactive protein (hs-CRP) levels, complication rates, immediate post-operative stone-free rate (RSFR), and long-term stone-free rate (LSFR). RESULTS: The comparative analysis of patient age, body mass index (BMI), stone size, computed X-ray tomography (CT) value of stones, number of stones, and comorbidities revealed no statistically significant differences between the mPCNL and FURSL groups (p>0.05). The mPCNL cohort exhibited a markedly lower duration of operation (p<0.001) and BCS score (p<0.001) compared to the FURSL cohort. Nonetheless, the mPCNL cohort demonstrated significantly higher hospitalization expenses (p<0.001), length of hospital stay (p<0.001), VAS score for pain (p<0.001), and level of hemoglobin decrease (p<0.001) in comparison to the FURSL cohort. Moreover, the immediate post-operative stone-free rate (RSFR) was significantly higher in the mPCNL group (p=0.007). The long-term stone-free rate (LSFR), however, showed no significant difference between the two groups (p=0.160). Furthermore, the FURSL group exhibited significantly fewer overall complications in contrast to the mPCNL group (p=0.006). CONCLUSIONS: mPCNL and FURSL are both safe and effective surgical methods for treating 2-3 cm renal calculi in women. However, FURSL holds distinct advantages, including minimally invasive procedure, accelerated recovery, reduced cost, and lower incidence of complications.

[Effects of bilobated superficial peroneal artery perforator flap in repairing two adjacent wounds of the fingers].

Objective: To investigate the therapeutic efficacy of bilobated superficial peroneal artery perforator flap in repairing two adjacent wounds of the fingers. Methods: A retrospective observational study was conducted. From January 2021 to January 2022, 15 patients with two adjacent wounds of the fingers who met the inclusion criteria were hospitalized in Suzhou Ruihua Orthopaedic Hospital, including 10 males and 5 females, aged 25 to 51 years. The area of single wound after debridement was from 2.5 cm×2.0 cm to 7.5 cm×2.5 cm. All the wounds were repaired by the bilobated superficial peroneal artery perforator flap from the lower leg. The single lobe area of bilobated flap was from 3.0 cm×2.0 cm to 8.0 cm×3.0 cm. The wounds in all the donor sites were sutured directly. During the operation, the number of resected flaps, the number and type of carried perforators were recorded, and the calibers of perforator and superficial peroneal artery and the length of vascular pedicle were measured. The survival of flap and the wound healing in the donor and recipient sites were recorded after operation. The recovery of donor and recipient sites were recorded during follow-up. At the last follow-up, the repair effect of flap was evaluated by the comprehensive evaluation scale, and the sensory function of flap was evaluated by the sensory function evaluation standard of British Medical Research Association. Results: During the operation, 15 bilobated flaps were successfully resected, carrying 36 superficial peroneal artery perforators, all of which were septocutaneous perforators with the caliber of 0.2-0.8 mm. The caliber of superficial peroneal artery was 0.4-1.1 mm and the length of vascular pedicle was 3-8 cm. After operation, all the flaps survived with no vascular crisis occurred, and the wounds in donor and recipient sites healed well. During the follow-up of 6 to 12 months, the color and texture of flaps were similar to those of normal tissue in the hand and the appearance of flap was good in 10 cases; the other 5 cases underwent the stage Ⅱ flap thinning and plastic surgery 6 months after operation due to the bloated appearance of flaps. There was only linear scar in the donor site of lower leg, with no obvious scar hyperplasia or pigmentation, and there was no obvious adverse effect on the sensation or motor function of the distal limbs in the donor area. At the last follow-up, the repair effect of flap of 15 patients was excellent in 11 cases and good in 4 cases, and the sensory function of the flap was evaluated as grade S2 in all cases. Conclusions: The bilobated superficial peroneal artery perforator flap has high proportion of septocutaneous perforator, and the blood supply is sufficient and reliable. Using this flap to repair two adjacent wounds of the fingers causes minimal damage to the donor area, only one group of blood vessels is needed to be anastomosed to repair two wounds, the difficulty of microoperation is reduced, and good flap repair effect and sensory function can be obtained.

[Curative effects of the superficial peroneal artery perforator flap carrying multiple perforators in repairing hand and foot wounds].

Objective: To investigate the curative effects of the superficial peroneal artery perforator flap carrying two and more homologous perforators in repairing hand and foot wounds. Methods: A retrospective observational study was conducted. From January to September 2021, 23 patients with hand and foot wounds combined with bone or tendon exposure who met the inclusion criteria were admitted to Suzhou Ruihua Orthopaedic Hospital, including 16 males and 7 females, aged 23 to 68 years. After expansion of the wound, the wound area was 3.0 cm×2.0 cm to 11.0 cm×4.0 cm. All the wounds were repaired with the superficial peroneal artery perforator flap carrying two and more homologous perforators. The area of the resected flap was 4.0 cm×2.0 cm to 12.0 cm×5.0 cm. All the wounds in donor areas were sutured directly. During the operation, the resection of the flap, the number and caliber of carried perforators, the caliber of superficial peroneal artery, the length of vascular pedicle, and the number of accompanying veins of the superficial peroneal artery were recorded. The survival of the flap, the occurrence of complications, and the wound healing in the donor area were observed after operation. The recovery of the donor and recipient areas was followed up. At the last follow-up, the comprehensive evaluation scale was used to evaluate the curative effect of flap repair, and the sensory grading scale was used to evaluate the sensory function of the recipient area. Results: Totally 24 flaps were successfully resected in surgical operations, carrying 56 superficial peroneal artery perforators in total, with the caliber of perforators of 0.20-0.70 mm. The calibers of all perforators carried by 7 flaps were smaller than 0.40 mm. Nineteen flaps carried 2 perforators each, 3 flaps carried 3 perforators each, 1 flap carried 4 perforators, and 1 flap carried 5 perforators. During the operation, the superficial peroneal artery was resected with a caliber of 0.40-1.50 mm, the vascular pedicle was 2-6 cm in length, and each superficial peroneal artery had two accompanying veins. After operation, all the flaps survived smoothly, no vascular crisis or distal necrosis occurred, and the wounds healed well in the donor area. During the follow-up of 6 to 10 months after operation, the color, texture, and elasticity of the recipient area were good. Among them, 6 recipient areas were thinned and reshaped because of bloating. There was only linear scar and no obvious scar hyperplasia or pigmentation in the donor area, without significant change in sensory or motor function. At the last follow-up, the curative effect evaluation of flap repair was excellent in 22 flaps and good in 2 flaps, and the sensory function evaluation of the recipient area was grade S3 in 1 area and grade S2 in 23 areas. Conclusions: The superficial peroneal artery perforator flap with two and more homologous perforators has sufficient and reliable blood supply and is effective in repairing hand and foot wounds. It provides an ideal solution for the clinical problem in which the original operation scheme is abandoned due to the existence of only multiple slender perforators of caliber smaller than 0.40 mm, and only a single perforator in the operative field that cannot satisfy the needs of the flap blood supply and recipient area.

[Morphological study on the transverse branch of lateral femoral circumflex artery based on digital subtraction angiography].

Objective: To summarize the morphological characteristics of the transverse branch of lateral femoral circumflex artery (LFCA) using digital subtraction angiography (DSA) and explore its clinical significance. Methods: A retrospective observational study was conducted. From October 2020 to May 2021, 62 patients with soft tissue injuries in the extremities were hospitalized in Suzhou Ruihua Orthopedic Hospital, including 40 males and 22 females, aged from 20 to 72 years. DSA was performed in the lateral femoral region of patients before the anterolateral thigh flap transplantation, and in combination with imaging scale to observe and measure the general condition of the blood vessels and the occurrence (with the occurrence rate being calculated), source artery, location of the origin point, direction of course, and the location of the perforating point of the cutaneous perforator of the transverse branch of LFCA, and in addition to classify the morphological characteristics of the transverse branch. Results: DSA detection showed that the femoral artery, the deep femoral artery, and the branches of LFCA were clearly distinguishable in 62 patients. Transverse branches of LFCA were observed in 59 patients, including 52 cases with a single transverse branch, and 7 cases with double transverse branches. The occurrence rate of transverse branches was 95.2% (59/62). A total of 66 transverse branches of LFCA were observed, of which 3 originated from the deep femoral artery, and 63 originated from the LFCA. The origin point of the transverse branch was 6.5-12.7 cm away from the anterior superior iliac spine. The transverse branch which was approximately perpendicular to the long axis of the body, originated outwards, ran between the ascending branch of LFCA and the oblique branch of LFCA, and branched along the way, with the trunk running under the greater trochanter. The perforating point of the cutaneous perforator of the transverse branch was 8.0-18.0 cm away from the anterior superior iliac spine. In the classification of morphological characteristics of the transverse branch of LFCA, the most common type was the one that originated from the same trunk with other branches of LFCA, accounting for 50.0% (31/62), followed by the one that originated from the singular trunk of LFCA (12 cases) or deep femoral artery (3 cases), accounting for 24.2% (15/62); the special type accounted for 21.0% (13/62), including 7 cases of double transverse branches and 6 cases of the transverse branch originated from the same trunk with multiple other branches of LFCA; those with small/absent transverse branch only accounted for 4.8% (3/62). Among the above-mentioned common trunk relationship of two branches, those with shared trunk of ascending and transverse branches were most frequently observed, accounting for 77.4% (24/31); those with shared trunks of the transverse and oblique branches (5 cases) and the transverse and descending branches (2 cases) accounted for 22.6% (7/31) altogether. Conclusions: A high incidence rate of the transverse branch of LFCA is observed through DSA. The transverse branch originates from the lateral femoral artery approximately perpendicular to the long axis of the body, mainly from the same trunk with another main branch of LFCA, especially the ascending branch. This positioning analysis can provide an important reference for the design and resection of anterolateral femoral flaps.

[Clinical effects of anterolateral thigh flap with blood supply source of medial femoral perforator in repairing the wounds on extremities].

Objective: To investigate clinical effects of anterolateral thigh flap with blood supply source of medial femoral perforator in repairing the wounds on extremities. Methods: A retrospective observational study was conducted. From October 2018 to June 2021, Suzhou Ruihua Orthopedic Hospital admitted 12 patients (11 males and 1 female, aged 24-64 years) who met the inclusion criteria, and did not have the lateral circumflex femoral artery during anterolateral thigh flap resection, or changed to medial femoral perforator as a source of blood supply due to small perforator to repair the wound with flap transplantation. The wounds were on the upper limbs in 7 cases and on the lower limbs in 5 cases. The wound area after debridement was 8.0 cm×5.0 cm-24.0 cm×6.5 cm, and the applied flap area was 9 cm×6 cm-25 cm×7 cm. During transplantation, the perforating branch or source artery of the flap was anastomosed end to end with the vascular pedicle of the recipient area. Subcutaneous beauty suture was performed on all the donor wounds. After operation, the survival of the flap and vascular crisis were observed; and the wound healing at the donor site was observed. During follow-up, the texture of the flap and complications at the donor site were observed. At the last follow-up, the effect of flap repair was evaluated by using the modified self-made comprehensive efficacy rating table. Results: After operation, all the flaps of patients survived without vascular crisis; the wounds in the donor site healed smoothly. During follow-up of 6 to 26 months, the flaps had good texture; only linear scars remained in the donor area without scar contracture, pain or other discomfort. At the last follow-up, the total score of flap repair effect of 12 patients was 75-95, with an average of 87, of which 5 cases were rated as excellent, 6 cases as good, and 1 case as fair, and the proportion of excellent and good patients was 11/12. Conclusions: The application of anterolateral thigh flap with blood supply from the medial femoral perforator to repair wounds on extremities is an alternative method for the vascular variations such as no descending branch, oblique branch, or small perforator of the lateral circumflex femoral artery during the resection of the anterolateral thigh flap. This operation has the advantages of simple operation, small trauma, and others, which effectively ensures the smooth operation.

[Molecular features of 109 patients with chronic myelomonocytic leukemia in a single center].

Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.

[Exploration of the clinical application of combined endoscopic and laparoscopic surgery in early gastric cancer: 15 cases].

Objective: To investigate the application of combined gastroscopy and laparoscopy (dual scope) in the treatment of early gastric cancer. Methods: In this descriptive case series study, we retrospectively collected data on 15 patients with cT1b stage gastric cancer who had undergone combined laparoscopic and endoscopic surgery in the 900th Hospital of the People's Liberation Army of China from May 2020 to October 2022. The study cohort comprised nine men and six women of median age 59 (range: 47-76) years and median body mass index 20.9 (range: 18.3-26.2) kg/m2. Seven of the lesions were located on the lesser curvature of the gastric antrum and eight in the gastric angle. All lesions were biopsied for pathological examination and evaluated by endoscopic ultrasonography, followed by endoscopic submucosal dissection (ESD) and laparoscopic regional lymph node dissection. Studied variables included surgical and pathological features, postoperative factors, and outcomes. Results: In this group of patients, the median (range) operative time for ESD was 45 (30-82) minutes, the duration of laparoscopic lymph node dissection (45.1±8.6) minutes, and the median (range) intraoperative blood loss during lymph node dissection 30 (10-80) mL. Of the 13 patients with negative postoperative horizontal margins, four were stage SM1 and had no lymph node metastases (Stage SM1) and nine were Stage SM2, of which had one positive regional lymph node and two received additional standard distal gastrectomy with D2 lymphadenectomy concurrently because of positive ESD specimens (lymph node negative). No lymph node metastases were found in the surgical specimens of these patients. The remaining two patients had positive vertical margins; both had undergone concurrent standard distal gastrectomy with D2 lymphadenectomy. One of them was found to be lymph node positive (No. 3, one node). Four patients had impaired gastric emptying after dual-scope treatment, all of whom recovered well with symptomatic management; one patient with a suspected lymphatic leak was also managed conservatively. There were no cases of postoperative bleeding, abdominal infection, or incisional infection. At a median follow-up of 14 (6-26) months, no tumor recurrence or metastasis had been identified in any of the patients. Three patients had a grade B nutrition score 3 to 6 months after surgery, all of whom had undergone major gastrectomy, and two patients who had undergone dual-scope surgery reported an increase in acid reflux and belching after surgery compared with the preoperative period. Conclusion: A combined technique is safe and feasible for the treatment of early gastric cancer and is worthy of further exploration.

[Effect of pancreatic extracorporeal shock wave lithotripsy on chronic pancreatitis stones].

Objective: To analyze the therapeutic effect and safety of pancreatic extracorporeal shock wave lithotripsy(P-ESWL) for patients with chronic pancreatitis complicated by stones of the pancreatic duct and to investigate the influencing factors. Methods: A retrospective analysis was performed on clinical data from 81 patients with chronic pancreatitis complicated by pancreatic duct calculus treated with P-ESWL in the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi 'an Jiaotong University from July 2019 to May 2022. There were 55 males(67.9%) and 26 females(32.1%). The age was (47±15)years (range: 17 to 77 years). The maximum diameter(M(IQR)) of the stone was 11.64(7.60) mm, and the CT value of the stone was 869 (571) HU. There were 32 patients (39.5%) with a single pancreatic duct stone and 49 patients(60.5%) with multiple pancreatic duct stones. The effectiveness, remission rate of abdominal pain, and complications of P-ESWL were evaluated. Student's t test, Mann Whitney U test, χ2 test, or Fisher's exact test was used to compare the characteristics between the effective and ineffective groups of lithotripsy. The factors influencing the effect of lithotripsy were analyzed by univariate and multivariate logistic regression analysis. Results: Eighty-one patients with chronic pancreatitis were treated with P-ESWL 144 times, with an average of 1.78 (95%CI:1.60 to 1.96) times per person. Among them, 38 patients(46.9%) were treated with endoscopy. There were 64 cases(79.0%) with effective removal of pancreatic duct calculi and 17 cases(21.0%) with ineffective removal. Of the 61 patients with chronic pancreatitis accompanied by abdominal pain, 52 cases(85.2%) had pain relief after lithotripsy. After lithotripsy treatment, 45 patients(55.6%) developed skin ecchymosis, 23 patients(28.4%) had sinus bradycardia, 3 patients(3.7%) had acute pancreatitis, 1 patient(1.2%) had a stone lesion, and 1 patient(1.2%) had a hepatic hematoma. Univariate and multivariate logistic regression analysis showed that the factors affecting the efficacy of lithotripsy included the age of patient(OR=0.92, 95%CI: 0.86 to 0.97), the maximum diameter of the stone(OR=1.12,95%CI:1.02 to 1.24) and the CT value of the stone(OR=1.44, 95%CI: 1.17 to 1.86). Conclusions: P-ESWL is effective in the treatment of patients with chronic pancreatitis complicated by calculi of the main pancreatic duct.Factors affecting the efficacy of lithotripsy include patient's age, maximum stone diameter, and CT value of calculi.

Uncertainty and influencing factors of the placement error of three-dimensional conformal intensity-modulated radiotherapy for thoracic tumors.

OBJECTIVE: Radiation therapy is an important method for the treatment of chest tumors. This study discussed the placement error of three-dimensional (3D) conformal intensity-modulated radiotherapy in patients with different types of chest tumors and analyzed the relevant influencing factors. PATIENTS AND METHODS: 100 patients with chest tumors diagnosed and treated in our hospital from March 2016 to March 2018 were randomly selected as research subjects, including 42 cases of esophageal cancer, 44 cases of breast cancer, and 14 cases of lung cancer. All patients underwent 3D conformal radiotherapy. The setup errors of patients with esophageal cancer, breast cancer, and lung cancer were detected after 3D conformal radiotherapy. Besides, the influencing factors of 3D conformal for thoracic tumors were analyzed by multiple linear regression analysis. RESULTS: After 3D conformal radiotherapy, the systematic errors of patients with esophageal cancer in X-axis, Y-axis, and Z-axis were -0.10, 1.26 and 0.07, respectively, while the random errors in X-axis, Y-axis, and Z-axis were 1.18, -1.14, and 0.97 respectively. The times for the absolute values of the positioning error with a range of ≤5 mm in X-axis, Y-axis, and Z-axis were 40 (95.24%), 2 (4.76%) and 36 (85.71%), while these with a range of >5 mm in X-axis, Y-axis, and Z-axis were 6 (14.29%), 41 (97.62%) and 1 (2.38%), respectively. For patients with breast cancer, the systematic errors and random errors in X-axis, Y-axis, and Z-axis are -0.19, 1.19, and 0.15, as well as 0.97, 0.02 and 1.29, respectively. The times for the absolute values of the positioning error with a range of ≤5 mm and >5 mm were 41 (93.18%), 3 (6.82%), and 36 (81.82%), as well as 8 (18.18%), 42 (95.45%) and 2 (4.55%), severally. For patients with lung cancer, the systematic errors and random errors in X-axis, Y-axis, and Z-axis were 0.14, 1.42, and 0.15, as well as 1.35, -0.23 and 1.12, respectively. The times for the absolute values of the positioning error with the range of ≤5 mm and >5 mm were 14 (93.33%), 1 (6.67%), and 11 (73.33%), as well as 4 (26.67%), 14 (93.33%) and 1 (6.67%) after 3D conformal radiotherapy. After multiple linear regression analyses, gender and lung volume were the influencing factors of Z-axis setup error, and the lesion location was the influence factor of Y-axis setup error (p<0.05). CONCLUSIONS: There are certain positioning errors in the X-axis, Y-axis, and Z-axis directions of thoracic tumors receiving 3D conformal radiotherapy. Gender, lung volume, and lesion location are all important factors that affect the placement error. The results of this study provide a certain reference for the positioning error of radiation therapy for thoracic tumors, which is conducive to improving the accuracy of radiotherapy and better protecting the surrounding tissues.

Optimal biopsy site for the diagnosis of oral pemphigus vulgaris and mucous membrane pemphigoid: a systematic review and meta-analysis.

The aim of this study was to critically evaluate the diagnostic yields of direct immunofluorescence (DIF) analysis on perilesional and normal-appearing mucosa biopsy samples, to determine the optimal biopsy site for patients presenting with oral pemphigus vulgaris (PV) or mucous membrane pemphigoid (MMP). Electronic databases and article bibliographies were searched in December 2022. The primary outcome was the rate of DIF positivity. Of 374 records identified after the elimination of duplicates, 21 studies with 1027 samples were ultimately included. Meta-analysis revealed a pooled DIF positivity rate of 99.6% (95% confidence interval (CI) 97.4-100.0%, I2 = 0%) for PV and 92.6% (95% CI 87.9-96.5%, I2 = 44%) for MMP for biopsies from perilesional sites, and of 95.4% (95% CI 88.6-99.5%, I2 = 0%) for PV and 94.1% (95% CI 86.5-99.2%, I2 = 42%) for MMP for biopsies from normal-appearing sites. For MMP, there was no significant difference in the rate of DIF positivity between the two biopsy sites (odds ratio 1.91, 95% CI 0.91-4.01, I2 = 0%). The results suggest that the perilesional mucosa remains the optimal biopsy site for DIF diagnosis of oral PV, while the normal-appearing mucosa biopsy is optimal for oral MMP.

[Chemical reprogramming of human embryonic fibroblasts into neural progenitor cells in vitro].

OBJECTIVE: To establish a protocol for reprogramming human embryonic fibroblasts (HEFs) into chemically induced neural progenitor cells (ciNPCs). METHODS: In the two-staged reprogramming of HEFs, the intermediate compact cell colonies were first chemically induced in KSR medium containing small-molecule compounds (VCR) for 15 days in normoxia, followed by the lineage-specific induction stage, in which the compact cell colonies were digested with 0.25% trypsin and the cells were cultured in low adhesion plates. After formation of a large number of free-floating neurospheres 2 days later, the ciNPCs were labeled with CM-DiI and transplanted into rat models of Parkinson's disease (PD)to observe the survival, migration and differentiation of the cells in PD brain. RESULTS: After induction with VCR for 10 days under normoxic condition, compact cell colonies occurred in HEF cultures (approximately 40 colonies in each well containing 1×105 HEFs), and most of the colonies expressed high levels of alkaline phosphatase. A large number of free-floating neurospheres formed 2 days after passage and were defined as P1 ciNPCs. These ciNPCs exhibited typical neurosphere-like structures and expressed NPC-specific markers (nestin, Sox2, and Pax6). Under neuronal or glial differentiation condition, the ciNPCs expressed the neuron-specific marker Tuj1 and the astrocyte-specific marker GFAP. These ciNPCs could differentiate into Tuj1+, GFAP+, TH+ and GABA+ cells 4 weeks after transplantation into the brain of PD rats. CONCLUSION: HEFs can be directly reprogrammed into ciNPCs using smallmolecule compounds without the need of introducing exogenous genes. This success may provide a solution to the shortage of donor materials for neuroscience research and treatment of neurodegenerative diseases.

[Difficulties and challenges of pelvic exenteration in locally advanced rectal cancer].

In recent years, with advances in pelvic oncology and surgical techniques, surgeons have redefined the boundaries of pelvic surgery. Combined pelvic exenteration is now considered the treatment of choice for some patients with locally advanced and locally recurrent rectal cancer, but it is only performed in a few hospitals in China due to the complexity of the procedure and the large extent of resection, complications, and high perioperative mortality. Although there have been great advances in oncologic drugs and surgical techniques and equipment in recent years, there are still many controversies and challenges in the preoperative assessment of combined pelvic organ resection, neoadjuvant treatment selection and perioperative treatment strategies. Adequate understanding of the anatomical features of the pelvic organs, close collaboration of the clinical multidisciplinary team, objective assessment and standardized preoperative combination therapy creates the conditions for radical surgical resection of recurrent and complex locally advanced rectal cancer, while the need for rational and standardized R0 resection still has the potential to bring new hope to patients with locally advanced and recurrent rectal cancer.

Unintrusive multi-cancer detection by circulating cell-free DNA methylation sequencing (THUNDER): development and independent validation studies.

BACKGROUND: Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas. PATIENTS AND METHODS: A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world. RESULTS: MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance. CONCLUSION: In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.

Setup error of electronic portal image device in IMRT for thoracic tumors and its influence.

OBJECTIVE: The aim of this study was to analyze the setup error of the electronics portal image device (EPID) in intensity-modulated radiation therapy (IMRT) for thoracic tumors and the influence on the outward expansion distance of the target area. PATIENTS AND METHODS: A total of 202 patients with chest tumors admitted to our hospital from March 2016 to March 2018 were selected as the observation subjects. All patients were treated with IMRT. The original plan was developed based on the SM90 obtained by the planning target volume (PTV) expansion method, and the new plan was obtained by shifting the isocenter coordinates of the treatment plan according to the positioning error value obtained by EPID. Before the treatment, EPID scans were performed. The electronic radiation field images (ERIs) were registered with the digitally reconstructed radiographic images (DRRs) generated by the treatment planning system using the image registration software, and the setup errors in the X, Y, and Z directions were further measured. The PTV was developed according to ERIs, and the setup error was simulated to obtain the PTV with 95% internal target volume (ITV) reaching the prescribed dose under the condition of a setup error. The outward expansion distance of clinical target volume (CTV) → PTV was calculated. RESULTS: In this experiment, the setup errors in X, Y, and Z directions were (-2.00±1.16) mm, (0.16±1.14) mm, and (-0.55±1.16) mm, respectively. The systematic error in the Z direction was -3.00 mm, and the random error in the X direction was 3.30 mm. The CTV → PTV outward expansion distance was set as 7, 8 and 7 mm in the X direction, Y direction and Z direction, respectively. At this time, under the presence of setup error, the PTV D95 and the ITV V100 in the new plan were (62.23±3.85) Gy and (97.51±1.56) %, respectively, effectively ensuring that 95% ITV of 90% patients reached the prescribed dose. In contrast, the ITV D95 and ITV V100 in the presence of setup error were (56.11±5.26) Gy and (90.15±3.12) %, respectively, at a CTV → PTV outward expansion distance of 5 mm, which could not guarantee that 95% ITV of 90% patients reached the prescribed dose. In the presence of a setup error, the double-lung 5 Gy irradiation of the total heart volume (V5), the double-lung 20 Gy irradiation of the total heart volume (V20), mean lung dose (MLD), mean heart dose (MHD), and D1 cm3 of the new plan increased by 0.89%, 0.29%, 0.13%, 0.06%, and 5 Gy, respectively, compared with the original plan. CONCLUSIONS: In general, the first treatment of radiotherapy in thoracic tumors mostly has a certain degree of setup error, which is most evident in the X direction. When the CTV → PTV outward expansion distance is set at 7, 8, and 7 mm in the X direction, Y direction, and Z direction, respectively, it can effectively ensure that 95% ITV reach the prescribed dose in 90% of patients in the presence of a setup error. EPID helps to achieve the desired effect of radiotherapy, improves the efficacy of radiotherapy, and reduces the side effects caused by radiotherapy errors.

[A meta-analysis of risk factors for multidrug-resistant tuberculosis in China].

Objective: To explore the main risk factors of multidrug-resistant tuberculosis (MDR-TB) in China and to provide evidence-based evidence for MDR-TB preventon and control. Methods: All relevant literatures were searched in thedatabases, such as Pubmed, Web of Science and CNKI, Wanfang, VIP and SinoMed from 2000 to 2021. Quality evaluation and data extraction were carried out, and then a meta-analysis was performed using Stata 16.0 software. Results: A total of 59 literatures (36 cross-sectional and 23 case-control) including 75 793 participants were included in this study, and meta-analysis results showed age (OR=1.27, 95%CI: 1.05-1.54), education level (OR=1.29, 95%CI: 1.02-1.65), positive sputum smear (OR=2.56, 95%CI: 1.09-6.04), pulmonary cavity (OR=1.99, 95%CI: 1.57-2.52), course of disease (OR=4.25, 95%CI: 1.95-9.30), history of tuberculosis treatment (OR=6.42,95%CI:5.40-7.63), treatment interruption (OR=2.81, 95%CI: 1.50-5.29), irregular medication (OR=5.02, 95%CI: 2.95-8.54), adverse drug reactions (OR=4.27, 95%CI: 2.22-8.19), combined chronic obstructive pulmonary disease (COPD) (OR=2.21, 95%CI: 1.45-3.37), tuberculosis exposure history (OR=1.99, 95%CI: 1.36-2.91), smoking history (OR=1.35, 95%CI: 1.09-1.66) and floating population (OR=1.60, 95%CI: 1.04-2.44) were associated with the occurrence of MDR-TB. Conclusions: The high risk groups were farmer, low education level, pulmonary cavity, long course of disease, history of tuberculosis treatment, treatment interruption, irregular medication, adverse drug reaction, co-COPD, contact history of tuberculosis, smoking history, rural residence, and floating population. We should pay attention to high-risk groups, strengthen management and take effective measures such as early screening, knowledge education on tuberculosis, standardized and personalized treatment and whole-course supervision.