[Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study].

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

[Methylthioadenosine phosphorylase and p16 as surrogate diagnostic markers for CDKN2A homozygous deletion in brain tumors].

Objective: To examine whether immunohistochemistry of methylthioadenosine phosphorylase (MTAP) and p16 could be used to predict the CDKN2A status in various brain tumors. Methods: A total of 118 cases of IDH-mutant astrocytomas, 16 IDH-wildtype glioblastoma, 17 polymorphic xanthoastrocytoma (PXA) and 20 meningiomas diagnosed at Xuanwu Hospital, Capital Medical University, Beijing, China from November 2017 to October 2023 were collected and analyzed. The CDKN2A status was detected by using fluorescence in situ hybridization or next-generation sequencing. Expression of MTAP and p16 proteins was detected with immunohistochemistry. The association of loss of MTAP/p16 expression with CDKN2A homozygous/heterozygous deletion was examined. Results: Among the 118 cases of IDH-mutant astrocytoma, 13 cases showed homozygous deletion of CDKN2A. All of them had no expression of MTAP while 9 cases had no expression of p16. Among the 16 cases of IDH wild-type glioblastoma, 6 cases showed homozygous deletion of CDKN2A. All 6 cases had no expression of MTAP, while 3 of these cases had no expression of p16 expression. Among the 17 PXA cases, 4 cases showed homozygous deletion of CDKN2A, and the expression of MTAP and p16 was also absent in these 4 cases. Among the 20 cases of meningiomas, 4 cases showed homozygous deletion of CDKN2A. Their expression of MTAP and p16 was also absent. Among the four types of brain tumors, MTAP was significantly correlated with CDKN2A homozygous deletion (P<0.05), with a sensitivity of 100%. However, it was only significantly correlated with the loss of heterozygosity (LOH) of CDKN2A in astrocytomas (P<0.001). P16 was associated with CDKN2A homozygous deletion in IDH-mutant astrocytoma and PXA (P<0.001), but not with the LOH of CDKN2A. Its sensitivity and specificity were lower than that of MTAP. Conclusions: MTAP could serve as a predictive surrogate for CDKN2A homozygous deletion in adult IDH-mutant astrocytoma, PXA, adult IDH-wildtype glioblastoma and meningioma. However, p16 could only be used in the first two tumor types, and its specificity and sensitivity are lower than that of MTAP.

[Clinical application of photobiomodulation in trauma repair and medical aesthetics].

In recent years, with the deepening of researches on the molecular biological mechanisms of photobiomodulation (PBM), PBM has gradually been applied in clinical practice, providing effective treatment methods and approaches for various diseases. Compared with traditional photothermal therapy, PBM has the characteristics of good therapeutic effect, almost no adverse reaction, and simple operation, and its clinical efficacy is becoming increasingly significant. This article provides a detailed explanation on the mechanism of PBM, its application characteristics and development trends in trauma repair and medical aesthetics, in order to provide a theoretical basis for the extensively clinical application of this therapy.

[A case of high-pressure injection injury of hand complicated with deep chemical burn caused by industrial cement].

This article reports a patient with extensive high-pressure injection injury of the hand combined with deep chemical burn caused by high-pressure injection of industrial cement materials was diagnosed and treated in the Department of Hand Surgery, Xiaolan Hospital Affiliated to Southern Medical University in 2022. The nerves, tendons and blood vessels of the left hand were involved, and the ulnar skin of the left thumb was extensively necrosis, and a large number of extensive cement foreign bodies remained under the skin. Part of the cement was inserted into the joint capsule of the interphalangeal joint. After emergency surgical treatment, the patient was saved successfully, and the wound healed well without chemical poisoning and other related complications, which created conditions for the second stage of flap repair.

[Association between CD4+T lymphocyte and body composition with physical frailty among elderly HIV-infected patients in Chongqing City].

Objective: To identify the association between CD4+T lymphocyte (CD4) counts and physical frailty among HIV-infected people aged 65 years and older, and evaluate whether this association will be modified by the indicators of body composition. Methods: From May to October 2022, 485 elderly HIV-infected patients receiving antiretroviral therapy (ART) were recruited from 7 antiviral treatment sites in Jiangjin District Center for Disease Control and Prevention, Chongqing. The data of basic characteristics (age and gender), living habits (smoking and drinking) and disease history (metabolic diseases, cardiovascular and cerebrovascular diseases, respiratory disease and malignant tumors) were collected through the face-to-face investigation with self-made questionnaires. Fried Frailty Scale was used to evaluate the status of physical frailty. Physical fitness (walking speed, grip strength, height, and weight) and body composition (skeletal muscle mass, body fat mass, and basal metabolic rate) were measured. The antiretroviral treatment data were obtained from the China AIDS Integrated Prevention and Treatment Data information management system. The prevalence of physical frailty was calculated among the HIV-infected patients. The potential effects of CD4 counts on physical frailty were explored by using multivariate logistic regression. Subgroup analyses were repeated in the logistic regression with muscle mass, body fat mass, and other indicators of body composition as subgroup variables to determine whether the association might be modified by body composition. Results: The age of 485 patients were (72±5) years old, of which 48.2% (234 cases) were>70 years old and 70.9% (344 cases) were male, and all of whom had initiated the ART treatment. The prevalence of physical frailty among these patients was 7.4% (36/485). Multivariate logistic regression showed that after adjusting for age, sex, smoking, drinking, body composition index, ART duration, viral load and the number of comorbidities, increased CD4 cell level was associated with decreased prevalent risk of physical frailty among elderly HIV-infected patients. For every increase of 5.0×107 CD4 cells/L, the prevalent risk of physical frailty decreased by 12% [OR (95%CI): 0.88 (0.76-1.01)]. Compared with the low CD4 cell level group, the risk of physical frailty in those with normal CD4 cell level decreased by 69% [OR (95%CI): 0.31 (0.10-0.92)]. Subgroup analysis of body composition indicators showed that the protective effect of normal CD4 cell level on physical frailty was more pronounced in the high skeletal muscle mass and high basal metabolic rate group (Pinteraction<0.05). Conclusion: The prevalence of physical frailty among elderly HIV-infected patients is relatively lower in Chongqing, and the CD4 cell level, skeletal muscle mass and basal metabolic rate are related to physical frailty.

[A prospective cohort study of factors associated with longevity in older adults in 10 areas of China].

Objective: To evaluate the associations of sociodemographic characteristics and lifestyle factors with longevity status in older adults in China. Methods: After excluding those born after 31st December 1938, a total of 51 870 older adults from the China Kadoorie Biobank (CKB) were included. The attained age was defined according to the survival age or age on 31st December 2018. According to the attained age, the old persons were categorized into non-longevity (died before age 80 years) and longevity (attained age ≥80 years). The longevity group was further divided into two groups: longevity with death occurring before 2019, and longevity and survival to 2019. The information about socio-demographic characteristics and lifestyles was collected at the 2004-2008 baseline survey. Multinomial logistic regression models were used to analyze the associations between exposure factors and outcomes by taking the non-longevity group as the reference group. Results: A total of 51 870 older adults aged 65-79 years in the baseline survey were included for analysis. During a follow-up for (10.2±3.5) years, 38 841 participants were longevity, and 30 354 participants still survived at the end of 2018. Compared to men, rural populations, non-married individuals, those with an annual household income of less than 10 000 yuan, and those with education levels of primary school or below, the adjusted ORs(95%CI) for longevity and survival to 2019 in women, urban residents, married individuals, those with annual household incomes ≥20 000 yuan, and those with education levels of college or university were 1.68 (1.58-1.78), 1.69 (1.61-1.78), 1.15 (1.10-1.21), 1.44 (1.36-1.53), and 1.32 (1.19-1.48), respectively. The OR (95%CI) for longevity and survival to 2019 was 1.09 (1.08-1.10) for those with an increase of 4 MET-hour/day in total physical activity level. With those who never or almost never smoked, had no alcohol drinking every week, had normal weight (BMI: 18.5-23.9 kg/m2), and WC <85 cm (man)/<80 cm (woman) as the reference groups, the ORs(95%CI) of longevity and survival to 2019 were 0.64 (0.60-0.69) for those smoking ≥20 cigarettes per day, 1.29 (1.14-1.46) for those with alcohol drinking every week, 1.13 (1.01-1.26) for those with pure alcohol drinking <30 g per day, 0.56 (0.52-0.61) for those being underweight, 1.27 (1.19-1.36) for those being overweight, 1.23 (1.11-1.36) for those with obesity, and 0.86 (0.79-0.93) for those with central obesity. Further stratified analysis by WC was performed. In the older adults with WC <85 cm (man)/<80 cm (woman), the ORs (95%CI) of longevity and survival was 1.80 (1.69-1.92) for those with each 5 kg/m2 increase in BMI and 1.02 (0.96-1.08) for those with WC ≥85 cm (man)/≥80 cm (woman). There was a statistically significant difference in the association between BMI and longevity between the two WC groups (interaction test P<0.001). Conclusion: This study showed that women, the married, those with higher socioeconomic status and education level, and those with healthy lifestyles were more likely to achieve longevity.

[Long-term follow-up of humanized and murine CD19 CAR-T-cell therapy for B-cell acute lymphoblastic leukemia].

Objective: Murine CD19 chimeric antigen receptor T-cell (CAR-T) products have been approved for the treatment of refractory/relapsed (R/R) B-cell acute lymphocytic leukemia (B-ALL) ; moreover, humanized products are also undergoing clinical trials. This study aimed to explore the differences in safety and short- and long-term follow-up efficacy between humanized and murine CD19 CAR-T-cells for treating relapsed and refractory B-ALL. Methods: Clinical data of 80 patients with R/R B-ALL treated with CD19-targeted CAR-T-cells at the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between May 2016 and March 2023 were analyzed, which included 31 patients with murine CAR-T and 49 with humanized products. Results: The proportion of patients with cytokine-release syndrome (CRS) in the murine and humanized groups was 63.1% and 65.3%, respectively. Moreover, a higher proportion of patients suffered from severe CRS in the murine group than in the humanized CAR-T group (19.4% vs 8.2%, P=0.174). Furthermore, one patient per group died of grade 5 CRS. The incidence of grade 1-2 immune effector cell-associated neurotoxicity syndrome (ICANS) was 12.9% and 6.1%, respectively; severe ICANS were not observed. Among patients receiving murine CAR-T-cells, an overall response (OR) was observed in 74.2%. Conversely, the OR rate of patients receiving humanized CAR-T-cells was 87.8%. During the median follow-up time of 10.5 months, the median recurrence-free survival (RFS) of patients with murine CAR-T-cells was 12 months, which was as long as that of patients with humanized CAR-T-cells. The median overall survival (OS) were not reached in both groups. Of the 45 patients with a bone marrow burden over 20% at baseline, humanized CAR-T therapy was associated with a significantly improved RFS (43.25% vs 33.33%, P=0.027). Bridging transplantation was an independent factor in prolonging OS (χ(2)=8.017, P=0.005) and PFS (χ(2)=6.584, P=0.010). Common risk factors, such as age, high proportion of bone marrow blasts, and BCR-ABL fusion gene expression, had no significant effect on patients' long-term follow-up outcomes. Three patients reached complete remission after reinfusion of humanized CAR-T-cells. However, one patient relapsed one month after his second infusion of murine CAR-T-cells. Conclusions: The results indicate that humanized CAR-T therapy showed durable efficacy in patients with a higher tumor burden in the bone marrow without any influence on safety. Moreover, it could overcome immunogenicity-induced CAR-T resistance, providing treatment options for patients who were not treated successfully with CAR-T therapies.

[To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia].

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

[Protective effect of intervention with cannabinoid type-2 receptor agonist JWH133 on pulmonary fibrosis in mice].

Objective: JWH133, a cannabinoid type 2 receptor agonist, was tested for its ability to protect mice from bleomycin-induced pulmonary fibrosis. Methods: By using a random number generator, 24 C57BL/6J male mice were randomly divided into the control group, model group, JWH133 intervention group, and JWH133+a cannabinoid type-2 receptor antagonist (AM630) inhibitor group, with 6 mice in each group. A mouse pulmonary fibrosis model was established by tracheal instillation of bleomycin (5 mg/kg). Starting from the first day after modeling, the control group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution, and the model group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution. The JWH133 intervention group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg, dissolved in physiological saline), and the JWH133+AM630 antagonistic group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg) and AM630 (2.5 mg/kg). After 28 days, all mice were killed; the lung tissue was obtained, pathological changes were observed, and alveolar inflammation scores and Ashcroft scores were calculated. The content of type Ⅰ collagen in the lung tissue of the four groups of mice was measured using immunohistochemistry. The levels of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in the serum of the four groups of mice were measured using enzyme-linked immunosorbent assay (ELISA), and the content of hydroxyproline (HYP) in the lung tissue of the four groups of mice was measured. Western blotting was used to measure the protein expression levels of type Ⅲ collagen, α-smooth muscle actin (α-SMA), extracellular signal regulated kinase (ERK1/2), phosphorylated P-ERK1/2 (P-ERK1/2), and phosphorylated ribosome S6 kinase type 1 (P-p90RSK) in the lung tissue of mice in the four groups. Real-time quantitative polymerase chain reaction was used to measure the expression levels of collagen Ⅰ, collagen Ⅲ, and α-SMA mRNA in the lung tissue of the four groups of mice. Results: Compared with the control group, the pathological changes in the lung tissue of the model group mice worsened, with an increase in alveolar inflammation score (3.833±0.408 vs. 0.833±0.408, P<0.05), an increase in Ashcroft score (7.333±0.516 vs. 2.000±0.633, P<0.05), an increase in type Ⅰ collagen absorbance value (0.065±0.008 vs. 0.018±0.006, P<0.05), an increase in inflammatory cell infiltration, and an increase in hydroxyproline levels [(1.551±0.051) µg/mg vs. (0.974±0.060) µg/mg, P<0.05]. Compared with the model group, the JWH133 intervention group showed reduced pathological changes in lung tissue, decreased alveolar inflammation score (1.833±0.408, P<0.05), decreased Ashcroft score (4.167±0.753, P<0.05), decreased type Ⅰ collagen absorbance value (0.032±0.004, P<0.05), reduced inflammatory cell infiltration, and decreased hydroxyproline levels [(1.148±0.055) µg/mg, P<0.05]. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group showed more severe pathological changes in the lung tissue of mice, increased alveolar inflammation score and Ashcroft score, increased type Ⅰ collagen absorbance value, increased inflammatory cell infiltration, and increased hydroxyproline levels. Compared with the control group, the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK proteins in the lung tissue of the model group mice increased, while the expression of type Ⅰ collagen, type Ⅲ collagen, and α-SMA mRNA increased. Compared with the model group, the protein expression of α-SMA (relative expression 0.60±0.17 vs. 1.34±0.19, P<0.05), type Ⅲ collagen (relative expression 0.52±0.09 vs. 1.35±0.14, P<0.05), P-ERK1/2 (relative expression 0.32±0.11 vs. 1.14±0.14, P<0.05), and P-p90RSK (relative expression 0.43±0.14 vs. 1.15±0.07, P<0.05) decreased in the JWH133 intervention group. The type Ⅰ collagen mRNA (2.190±0.362 vs. 5.078±0.792, P<0.05), type Ⅲ collagen mRNA (1.750±0.290 vs. 4.935±0.456, P<0.05), and α-SMA mRNA (1.588±0.060 vs. 5.192±0.506, P<0.05) decreased. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group increased the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK protein in the lung tissue of mice, and increased the expression of type Ⅲ collagen and α-SMA mRNA. Conclusion: In mice with bleomycin-induced pulmonary fibrosis, the cannabinoid type-2 receptor agonist JWH133 inhibited inflammation and improved extracellular matrix deposition, which alleviated lung fibrosis. The underlying mechanism of action may be related to the activation of the ERK1/2-RSK1 signaling pathway.

[Evaluation of the efficacy and safety of Nocardia rubra cell wall skeleton immunotherapy for cervical high-risk HPV persistent infection].

Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) Ⅰ and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINⅡ and more lesions after treatment with CINⅡ or CIN Ⅲ (CINⅡ/CIN Ⅲ). All participants were randomly divided into the test group and the control group at a ratio of 2∶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ2=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ2=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.

[Efficacy and safety of modified Hartel approach in the treatment of primary trigeminal neuralgia with radiofrequency thermocoagulation].

Objective: To assess the efficacy and safety of modified Hartel approach in the treatment of primary trigeminal neuralgia with radiofrequency thermocoagulation. Methods: A total of 89 patients with primary trigeminal neuralgia in Nanjing Drum Tower Clinical College of Xuzhou Medical University from July 2021 to July 2022 were prospectively included, and were divided into experimental group (n=45, modified Hartel approach: selecting 2.0 cm lateral to and 1.0 cm below angulus oris as insertion point) and control group (n=44, traditional Hartel approach: selecting 2.5 cm lateral to the angulus oris as insertion point) according to the random number table method. There were 19 males and 26 females in the experimental group, and aged (67.6±8.8) years. Meanwhile, there were 19 males and 25 females in the control group, and aged (64.8±11.7) years. All the patients were treated by CT-guided radiofrequency thermocoagulation. The success rate of one-time puncture, number of punctures, the time of puncture, operation time, numerical rating scale (NRS) scores and complications were recorded and compared between the two groups. Results: The success rate of one-time puncture in experimental group was 64.4% (29/45), which was higher than that in control group 31.8% (14/44) (P<0.05). The number of punctures [M (Q1, Q3)], the time of puncture [M (Q1, Q3)] and operation time in the experimental group were 1 (1, 2), 218 (206, 378) s, (19.9±2.7) min, which were less than those of control group [2 (1, 3), 390 (231, 598) s, (27.0±3.9) min] (all P<0.05). The NRS scores [M (Q1, Q3)] of 1 day, 1 month and 3 months after surgery in the experimental group were 1 (1, 2), 1 (0, 2) and 1(0, 1), respectively, which were lower than the baseline level [6 (6, 7)] (all P<0.05). The NRS scores [M (Q1, Q3)] of 1 day, 1 month and 3 months after surgery in the control group were 1 (1, 2), 1 (0, 2) and 1 (0, 2), respectively, which were lower than the baseline level [6 (6, 7)] (all P<0.05). There was no statistically significant difference in the incidence of nausea and vomiting, facial numbness, and decreased masticatory muscle strength between the two groups (all P>0.05) In the experimental group, two patients had puncture needles into the oral cavity, with timely detection and replacement of puncture needles, and no infection occurred. There was no cerebrospinal fluid leakage and decreased corneal reflex in both groups. Conclusion: The modified Hartel approach can significantly improve the success rate of one-time puncture via foramen ovale, reduce the operation time and the incidence of postoperative facial swelling, which is a safe and effective puncture method.

[Homozygous familial hypobetalipoproteinemia caused by APOB gene variations: a case report and review of literature].

Objective: To summarize the genotypes and clinical characteristics of homozygous family hypobetalipoproteinemia (Ho-FHBL) caused by apolipoprotein B (APOB) gene variations. Methods: The clinical, laboratory, genetic, and liver histology data of a boy with Ho-FHBL managed in the hepatology ward of the Children's Hospital of Fudan University in May 2021 were retrospectively analyzed. The literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China VIP database, China Biology Medicine disc and PubMed database (up to May 2022) with "familial hypobetalipoproteinemia" or "hypobetalipoproteinemias" or "hypo beta lipoproteinemia" or "hypolipoproteinemias" as the search terms. All relevant literatures were reviewed to summarize the clinical and genetic features of Ho-FHBL caused by APOB gene variations. Results: The male patient was admitted to the hospital due to abnormal liver function tests for 8 months at the age of 4 years and 6 months. Blood biochemistry showed transaminitis and abnormally low serum levels of lipids. Liver biopsy revealed fatty liver with inflammation and early cirrhosis (Brunt score was F3G2S4). Whole exome sequencing revealed two novel variants of APOB gene (c.3745C>T, p.Q1249 * from the father and c.4589_4592delinsAGGTAGGAGGTTTAACTCCTCCTACCT, p.T1530Kfs * 12 from the mother). He was diagnosed as Ho-FHBL caused by APOB gene compound heterozygous variations. Literature search retrieved 36 English literatures and 0 Chinese literature. A total of 55 (23 males and 32 females) Ho-FHBL cases, including this one, were caused by 54 APOB gene pathogenic variants (23 frameshift, 15 nonsense, 7 missense, 8 splice and 1 gross deletions). The age of the last follow-up was between 1 month and 75 years. Among them, 28 cases had lipid malabsorption, 19 cases had early dysplasia, 12 cases had no symptoms. Twenty-one patients had symptoms related to fat soluble vitamin deficiency, including 14 cases of acanthocytosis, 10 cases of neurological symptoms, and 6 cases of ocular lesions. Thirty-four patients had liver involvement, including 25 cases of elevated transaminase, 21 cases of fatty liver, 15 cases of hepatomegaly, 9 cases of liver fibrosis, 3 cases of liver cirrhosis, 1 case of hepatic hemangioma and 1 case of liver neoplastic nodule. Conclusions: The variants of APOB gene in Ho-FHBL are mainly frameshift and nonsense variations. Patients may have lipid malabsorption and (or) early dysplasia, or symptom-free. Liver involvement is common.

[Changes of the World Health Organization 2022 classification (5th edition) of salivary glands tumors].

Pathological diagnosis of salivary gland tumors is one of the most challenging areas in all head and neck surgical pathology. The classification of salivary gland tumors was updated in the 5th edition of the World Health Organization Classification of Head and Neck Tumours, most of which were based on their molecular pathological characteristerics. This new classification features a description of several new entitiesamong benign and malignant neoplasms, salivary gland tumors with updated naming or diagnostic criteria, and lesions deleted from this section, etc.This present review focuses on the updates and changes in the new classification of salivary gland tumors, and provides some reference for head and neck surgeons and pathologists.

[Pancreas multidisciplinary team optimizes the diagnosis and treatment of pancreas-related diseases and improves the prognosis of pancreatic cancer patients].

Objectives: To evaluate the role of pancreas multidisciplinary team(MDT) clinic in the diagnosis of pancreatic diseases,patient compliance with MDT advice,and the impact of MDT on the postoperative survival of patients with pancreatic cancer. Methods: The study included 927 patients(554 males,373 females,aged (58.1±13.3)years (range: 15 to 89 years)) that had visited the pancreas MDT clinic of Zhongshan Hospital from May 2015 to December 2021,and 677 patients(396 males, 281 females, aged (63.6±8.9)years(range: 32 to 95 years)) who underwent radical surgery and with pathologically confirmed pancreatic adenocarcinoma from January 2012 to December 2020,of whom 79 patients had attended the pancreas MDT. The clinical and pathological data were collected and analyzed retrospectively. Diseases were classified in accordance with 2010 WHO classification of tumors of the digestive system and usual clinical practices. The Kaplan-Meier method was used for drawing the survival curve and calculating the survival rate. The univariate analysis was done by Log-rank test and the multivariate analysis was done by COX proportional hazards model. Survival rates were compared using χ2 test. Results: Among the 927 patients that had visited the MDT clinic,233 patients(25.1%) were referred due to undetermined diagnosis. A direct diagnosis was made in 109 cases (46.8%,109/233) by the MDT clinic, of which 98 were consistent with the final diagnosis,resulting in an accuracy of 89.9%(98/109). The direct diagnosis rate in the recent years(36.6%(41/112),from June 2019 to December 2021) decreased compared to that in the previous years(56.2%(68/121),from May 2015 to May 2019),yet the accuracy in the recent years(90.2%,37/41) was basically the same as before (89.7%,61/68). The rate of compliance of the entire cohort was 71.5%(663/927), with the compliance rate in the recent two and a half years(81.4%,338/415) remarkably higher than that in the previous four years(63.4%,325/512). Patients with pancreatic cancer that attended the MDT exhibited a trend toward longer median postoperative survival than patients that did not attend the MDT,but the difference was not statistically significant(35.2 months vs.30.2 months,P>0.05). The 1-year and 3-year survival rates of patients that attended the MDT were significanly higher than patients that did not attend the MDT(88.6% vs. 78.4%,P<0.05;32.9% vs. 21.9%,P<0.05,respectively),but the 5-year survival rate was not statistically different(7.6% vs. 4.8%,P>0.05). Conclusions: The pancreas MDT clinic is an accurate and convenient way to diagnose intractable pancreatic diseases,and in the recent years the patients' compliance rate with MDT advice has increased. Pancreatic cancer patients that have attended the MDT have higher 1-year and 3-year postoperative survival rates,but the long-term survival benefits of MDT still needs to be proved by clinical studies on a larger scale.

[Effectiveness of different epidural coverage materials for preventing postoperative scar hyperplasia and dural adhesion in spine].

Objective: To analyze the effects and mechanisms of three commonly used epidural coverings, gelatin sponge, bovine Achilles tendon extract collagen and polyester urethane fiber, in preventing epidural scar adhesions after laminectomy in rats. Methods: Forty-eight adult Wistar rats were excised from L2 to L5 lamina to establish laminectomy models, and were divided into four groups with random number table according to different covering materials (12 rats in each group): blank group (group A), gelatin sponge group (absorbable, group B), polyester urethane fiber group (non-absorbable, group C) and bovine Achilles tendon extract collagen group (absorbable, group D). At 4 and 12 weeks postoperatively, the spinal tissues of the operated area were taken for gross observation (Rydell scar adhesion rating criteria) and histological observation (Nussbaum criteria); and the expression of three scar proliferation-related cytokines, basic fibroblast growth factor (bFGF), growth transforming factor ß1 (TGF-ß1) and vascular endothelial growth factor (VEGF), were measured in the peridural tissues. The differences between the indices in each group were analyzed and compared. Results: All 48 rats survived, and gross and histological findings at 4 and 12 weeks showed no dural adhesions in the gelatin sponge and bovine Achilles tendon extract collagen groups, adhesions in the polyester urethane fiber group, and heavy adhesions and spinal cord compression in the blank control group. There were significant differences in the Rydell grade and Nussbaum histological score between the absorbable material group and the non-absorbable group (both P<0.05). Western protein blotting at 4 and 12 weeks confirmed that the expression levels of three cytokines, including bFGF, TGF-ß1, and VEGF, were lower in the absorbable material group than those in the non-absorbable group (all P<0.01). Immunofluorescence tests at 12 weeks confirmed that the expression of bFGF, TGF-ß1 and VEGF were all lower in the gelatin sponge group (9.81±0.81, 12.42±2.35, 8.63±1.76) and the bovine Achilles tendon extract collagen group (12.70±2.02, 8.23±1.03, 10.19±2.67) than those in the polyester urethane fiber group (33.94±2.03, 30.29±2.76, 25.79±1.21) (all P<0.01). Conclusions: Bovine achilles tendon extract collagen and gelatin sponge can effectively reduce the hyperplasia of scar and dural adhesions after spinal surgery.

[Associations between sleep status and risk for kidney stones in Chinese adults: a prospective cohort study].

Objective: To analyze the associations between sleep status and the risk for kidney stone in Chinese adults. Methods: This study used baseline and long-term follow-up data of China Kadoorie Biobank. After excluding those with self-reporting of diagnosed chronic kidney disease and cancer and those with extreme values of sleep duration at baseline survey, 501 701 participants were included in this study. The information about their sleep status were collected, including insomnia symptoms, daytime sleepiness, nap habit, snoring and sleep duration. The sleep score was constructed based on insomnia symptoms, daytime sleepiness, and sleep duration, ranging from 0 to 3. Cox proportional hazards regression models were used to evaluate the association of sleep status with the risk for kidney stone, including individual sleep factors and combined sleep score. Results: During the follow-up for average (10.7±2.2) years, 12 381 cases of kidney stone were recorded for the first time. Compared with participants without insomnia symptoms, the multivariable-adjusted HR of kidney stone in those with difficulty falling asleep and waking up early were 1.12 (95%CI: 1.06-1.18) and 1.06 (95%CI: 1.00-1.12), respectively. There was no statistically significant association of kidney stone risk with sleeping pill use, daytime sleepiness, nap habit, or snoring. Compared with participants with sleep duration ≥7 hours per day, the HR of kidney stone in those with sleep duration <7 hours per day was 1.13 (95%CI: 1.08-1.18). Compared with participants with sleep score of 3 (highest sleep quality), the HR of kidney stone in those with sleep score of 2, 1, and 0 were 1.08 (95%CI: 1.03-1.13), 1.16 (95%CI: 1.10-1.23), and 1.19 (95%CI: 1.03-1.37), respectively. Conclusion: In China, adults with insomnia symptoms or short sleep duration have increased risk for kidney stone.

[Efficacy and safety of total neoadjuvant therapy versus neoadjuvant chemoradiotherapy in the treatment of locally advanced rectal cancer: a meta-analysis].

Objective: To systematically evaluate the efficacy and safety of total neoadjuvant therapy (TNT) in the comprehensive treatment of locally advanced rectal cancer. Methods: Literatures were screened from PubMed, Embase, Web of Science, Cochrane Library, CBM, Wanfang Data, VIP and CNKI from the inception date to May 2021 to collect the randomized controlled clinical trials (RCTs) of TNT followed by total mesorectal excision (TME) versus neoadjuvant chemotherapy (nCRT) followed by TME in the treatment of locally advanced rectal cancer. The data of overall survival, disease-free survival, R0 radical resection rate, pathological complete response (pCR) rate, T downstaging rate, the incidence of adverse events ≥ grade III, including neutropenia, nausea and vomiting, diarrhea, radiation dermatitis and nervous system toxicity, and the morbidity of complications within postoperative 30 days of the two groups were extracted from the included literatures. Review Manager 5.3 software was utilized for statistical meta-analysis. Results: Nine RCTs were finally enrolled including 2430 patients. Meta-analysis results showed that compared with nCRT group, patients in TNT group had longer overall survival (HR=0.80, 95%CI: 0.65-0.97, P=0.03) and higher pCR rate (RR=1.73, 95%CI: 1.44-2.08, P<0.01) with significant differences. Besides, there were no significant differences between two groups in disease-free survival (HR=0.86, 95%CI:0.71-1.05, P=0.14), R0 radical resection rate (RR=1.02, 95%CI: 0.99-1.06, P=0.17) and T downstaging rate (RR=1.04, 95%CI: 0.89-1.22, P=0.58) between two groups. In terms of treatment safety, the incidence of adverse events ≥ grade III (RR=1.09, 95%CI: 0.70-1.70, P=0.70) and morbidity of complications within postoperative 30 days (RR=1.07, 95%CI: 0.97-1.18, P=0.19) did not significantly differ between two groups. Conclusions: In the treatment of locally advanced rectal cancer, TNT may bring more survival benefits than nCRT and does not increase the incidence of adverse events and postoperative complications. Therefore, TNT could be used as a recommended treatment for patients with locally advanced rectal cancer.