ObjectiveTo characterize the seasonal patterns of influenza in Kunming City, Yunnan Province before, during, and after the COVID-19 pandemic, and provide scientific evidence for optimizing influenza prevention and control strategies. MethodsInfluenza-like illness (ILI) and etiological surveillance data for influenza from the 14^th week of 2010 to the 13^th week of 2024 in Kunming City of Yunnan Province were collected. Harmonic regression models were constructed to analyze the epidemic characteristics and seasonal patterns of influenza before (2010/2011‒2019/2020 influenza seasons), during (2020/2021‒2022/2023 influenza seasons), and after (2023/2024 influenza season) the COVID-19 pandemic. ResultsBefore the COVID-19 pandemic, influenza in Kunming City mainly exhibited an annual cyclic pattern without a significant semi-annual periodicity, peaking from December to February of the next year, with an epidemic duration of 20‒30 weeks. During the pandemic, influenza seasonality shifted, with an increase in semi-annual periodicity and an approximate one month delay in annual peaks. However, after the pandemic, the annual amplitude of influenza increased compared with that before the pandemic, and the epidemic duration extended by about one month. Although the annual peak largely reverted to the pre-pandemic levels, the annual peaks for different influenza subtypes/lineages had not fully recovered. ConclusionInfluenza seasonality in Kunming City underwent substantial alterations following the COVID-19 pandemic and has not yet fully reverted to pre-pandemic levels. Continuous surveillance on different subtypes/lineages of influenza viruses remains essential, and prevention and control strategies should be adjusted and optimized in a timely manner based on current epidemic trends.

In recent years, proton therapy technology has developed rapidly, and the number of patients treated with proton therapy has gradually increased. However, the application of proton therapy technology was far from practical needs. Because of the shortage of resources and the high cost, proton therapy systems are not accessible and affordable for most patients. In order to change this situation, it is necessary to develop a new truly practical proton therapy system based on clinical needs. Conceptual design of a practical proton therapy system was proposed. Compared with the existing system, one feature of the newly designed system is to reduce the maximum energy of the proton beam to 175~200 MeV; another feature is the configuration of deluxe and economical treatment rooms, the deluxe room is equipped with a rotating gantry and a six-dimensional treatment bed, and the economical room is equipped with a horizontal fixed beam and a patient vertical rotating setup device. This design can not only reduce the cost of proton therapy system and equipment room construction, but also facilitate the hospital to choose the appropriate configuration, which will ultimately benefit more patients.
Humans ; Proton Therapy ; Radiotherapy Planning, Computer-Assisted ; Hospitals ; Radiotherapy Dosage

Objective:To establish an automatic planning method using volumetric-modulated arc therapy (VMAT) for primary liver cancer (PLC) radiotherapy based on predicting the feasibility dose-volume histogram (DVH) and evaluate its performance.Methods:Ten patients with PLC were randomly chosen in this retrospective study. Pinnacle Auto-Planning was used to design the VMAT automatic plan, and the feasibility DVH curve was obtained through the PlanIQ dose prediction, and the initial optimization objectives of the automatic plan were set according to the displayed feasible objectives interval. The plans were accessed according to dosimetric parameters of the planning target volume and organs at risk as well as the monitor units. All patients′ automatic plans were compared with clinically accepted manual plans by using the paired t-test. Results:There was no significant difference of the planning target volume D 2%, D 98%, D mean or homogeneity index between the automatic and manual plans ((58.55±2.81) Gy vs.(57.98±4.17) Gy, (47.15±1.58) Gy vs.(47.82±1.38) Gy, (53.14±0.95) Gy vs.(53.44±1.67) Gy and 1.15±0.05 vs. 1.14±0.07, all P>0.05). The planning target volume conformity index of the manual plan was slightly higher than that of the automatic plan (0.77±0.08 vs. 0.69±0.06, P<0.05). The mean doses of normal liver, V 30Gy, V 20Gy, V 10Gy, V 5Gy and V< 5Gy of the automatic plan were significantly better than those of the manual plan ((26.68±11.13)% vs.(28.00±10.95)%, (29.96±11.50)% vs.(31.89±11.51)%, (34.88±11.51)% vs.(38.66±11.67)%, (45.38±12.40)% vs.(50.74±13.56)%, and (628.52±191.80) cm 3vs.(563.15±188.39) cm 3, all P<0.05). The mean doses of the small intestine, the duodenum, and the heart, as well as lung V 10 of the automatic plan were significantly less than those of the manual plan ((1.83±2.17) Gy vs.(2.37±2.81) Gy, (9.15±9.36) Gy vs.(11.18±10.49) Gy, and (5.44±3.10) Gy vs.(6.25±3.26) Gy, as well as (12.70±7.08)% vs.(14.47±8.11)%, all P<0.05). Monitor units did not significantly differ between two plans ((710.67±163.72) MU vs.(707.53±155.89) MU, P>0.05). Conclusions:The automatic planning method using VMAT for PLC radiotherapy based on predicting the feasibility DVH enhances the quality for PLC plans, especially in terms of normal liver sparing. Besides, it also has advantages for the protection of the intestine, whole lung and heart.

Objective: To explore the safety and effectiveness of left bundle branch area pacing (LBBAP) in children. Methods: Clinical data, pacing electrocardiogram and parameters of 6 patients (5 females and 1 male) who underwent permanent pacemaker implantation and LBBAP from January to June 2019 in the Department of Pediatric Cardiology of Anzhen Hospital were retrospectively analyzed. Results: The weight of the 6 patients aged between 9 and 14 years ranged from 26 to 48 kg. Five patients were diagnosed with third degree atrioventricular block, and 1 patient was diagnosed with cardiac dysfunction after right ventricular apical pacing. Cardiac function decreased in one patient and remained normal in the other five patients. Left ventricular end diastolic diameter (LVEDD) Z score was 1.85±0.65. V₁ lead showed changes like right bundle branch block in pacing electrocardiogram. No significant difference was found regarding QRS wave duration ((95±13) ms vs. (111±20) ms, t=-1.610, P>0.05) between preoperation and postoperation. Pacing threshold was (0.85±0.26) V. The sensing threshold was (15.0±4.3) mV and the impedance was (717±72) Ω. P potential was recorded in 3 cases. The earliest left ventricular local activation time was (56±5) ms and remained stable at different output voltages. Postoperative echocardiography revealed that the electrodes were located near the endocardium of the left ventricular septum. No complications such as myocardial perforation and electrode dislocation occurred during follow-up. The pacing threshold, sensing threshold and impedance were (0.60±0.09)V, (16.1±3.9)mV, (662±78)Ω respectively at 3 months after operation. The patient with low left ventricular ejection fraction (LVEF) recovered to normal on the 3 rd day after LBBAP (45% vs. 57%). The LVEDD Z score decreased to (1.1±0.3) at 3 months after operation and was significantly lower than that before operation (t=2.38, P<0.05). Conclusions LBBAP in children can achieve narrow QRS pacing andphysiological pacing with stablepacing parameters. It can improve left ventricular enlargement caused by long-term bradycardia, and cardiac dysfunction and cardiac enlargement caused by long-term right ventricular apical pacing quickly and effectively.LBBAP is safe and feasible for older children in the near future. However, the long term potential risks of LBBAP need further observation and study.

Objective To analyze the clinicopathological features and lymph node metastases characteristics of intrahepatic cholangiocarcinoma (ICC).Methods The retrospective case-control study was conducted.The clinicopathological data of 1 321 ICC patients who were admitted to 12 hospitals from April 2007 to November 2017 were collected,including 182 in the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University,173 in the First Affiliated Hospital of Xi'an Jiaotong University,156 in the First Hospital Affiliated to Army Medical University (Third Military Medical University),139 in the Cancer Center of Sun Yatsen University,128 in the Zhongshan Hospital of Fudan University,113 in the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine,109 in the First Affiliated Hospital of Dalian Medical University,84 in the Tianjin Medical University Cancer Institute and Hospital,65 in the First Affiliated Hospital of Zhengzhou University,62 in the Affiliated Hospital of North Sichuan Medical College,58 in the Affiliated Drum Tower Hospital of Nanjing University Medical School and 52 in the Second Affiliated Hospital of Zhejiang University School of Medicine.Treatment planning was respectively determined by comprehensive hospitals according to clinical features and results of related examinations.Surgical procedures were performed based on the results of intraoperative examinations and patients' conditions.Observation indicators:(1) laboratory examination and treatment situations;(2) relationship between clinicopathological features and primary tumor location and diameter;(3) diagnosis of lymph node dissection and metastases;(4) relationship between clinicopathological features and lymph node metastases.Measurement data with normal distribution were represented as x±s,and comparison between groups was done by the t test.Measurement data with skewed distribution were described as M (range).Comparison of count data were analyzed using the chi-square test.Results (1) Laboratory examination and treatment situations:of 1 321 patients,cases and percentages of positive hepatitis B virus (HBV),positive serum alpha-fetoprotein (AFP) (＞ 20 μg/L),positive serum carcinoembryonic antigen (CEA) (＞ 5 μg/L),positive serum alanine transaminase (ALT) (＞75 U/L),positive serum CA19-9 (＞37 U/mL) and positive serum total bilirubin (TBil) (＞20 μmol/L) were respectively 202,80,329,207,590,300 and 15.586％ (202/1 296),7.339％(80/1 090),26.299％ (329/1 251),16.587％ (207/1 248),49.789％(590/1 185),24.000％ (300/1 250).Of 1 321 patients,1 206 underwent surgery,including 904 with hepatectomy,193 with transcatheter arterial chemoembolization (TACE),72 with percutaneous transhepatic biliary drainage (PTBD),3 with endoscopic retrograde cholangiopancreatography (ERCP),3 with PTBD + ERCP and 31 with other treatments;115 had missing registration of surgical procedures.(2) Relationship between clinicopathological features and primary tumor location and diameter:① Relationship between clinicopathological features and primary tumor location:cases with CA19-9 level ≤ 37 U/mL,38-200 U/mL and ＞ 200 U/mL were respectively 227,91,146 with primary tumor located in left liver and 282,134,137 with primary tumor located in right liver.Cases combined with hepatitis and intrahepatic bile duct stone were respectively 67,73 with primary tumor in left liver and 111,47 with primary tumor in right liver,with statistically significant differences in above indictors (x2 =6.710,5.656,12.534,P＜0.05).The results of further analysis showed that incidence age of ICC was (63± 10)years old in patients with hepatitis and (59± 10) years old in patients without hepatitis,with statistically significant differences (t =4.840,P＜0.05).② Relationship between clinicopathological features and primary tumor diameter:cases with primary tumor diameter ≤ 3 cm,with 3 cm ＜ primary tumor diameter ≤ 5 cm and with primary tumor diameter ＞ 5 cm were respectively 159,250,229 with CEA level ≤ 5 pg/L and 40,65,95 with CEA level ＞ 5 μg/L and 165,258,286 with ALT level ≤ 75 U/L and 34,57,36 with ALT level ＞ 75 U/L and 148,242,281 with TBil level ≤ 20 μmol/L and 51,73,43 with TBil level ＞ 20 μmol/L,and 37,70 and 131 patients had satellite loci of tumor,with statistically significant differences in above indictors (x2=8.669,6.637,15.129,34.746,P＜0.05).(3) Diagnosis of lymph node dissection and metastases:of 904 patients with hepatectomy,346 received lymph node dissection,total number,number in each patient and median number of lymph node dissected were respectively 1 894.0,5.5 and 4.0 (range,1.0-26.0);157 had lymph node metastases,with a rate of lymph node metastasis of 45.376％ (157/346),number and number in each patient of positive lymph node were respectively 393.0 and 2.5.Of 346 patients with lymph node dissection,114 had lymph node metastasis by preoperative imaging examination,postoperative pathological examinations confirmed 64 with lymph node metastasis and 50 without lymph node metastasis;232 didn't have lymph node metastasis by preoperative imaging examination,postoperative pathological examinations confirmed 93 with lymph node metastasis and 139 without lymph node metastasis.The sensitivity,specificity and diagnostic accuracy by imaging examination were respectively 40.8％,73.5％ and 58.7％.(4) Relationship between clinicopathological characteristics and lymph node metastases:lymph node metastasis rate was respectively 51.397％ (92/179) in patients with primary tumor located in left liver,39.103％ (61/156) in patients with primary tumor located in right liver,34.615％(18/52) in patients with primary tumor diameter ≤ 3 cm,42.500％(51/120) in patients with 3 cm ＜ primary tumor diameter ≤ 5 cm,52.980％(80/151) in patients with primary tumor diameter ＞ 5 cm,48.790％(121/248) in patients with CEA ≤ 5 μg/L,59.302％ (51/86) in patients with CEA ＞ 5 μg/L,40.234％ (103/256) in patients with TBil ≤ 20 μmol/L,35.106％ (33/94) in patients with TBil ＞ 20 μmol/L,with statistically significant differences in above indictors (x2 =5.078,6.262,9.456,5.156,P ＜ 0.05).Conclusions The related etiological factors may be different due to different primary location of ICC.Primary tumor in left liver is significantly associated with intrahepatic bile duct stone of left liver,and primary tumor in right liver is associated with combined hepatitis,while combined hepatitis could lead early occurrence of ICC.At present,there is a low rate of lymph node dissection in ICC patients and a high lymph node metastasis rate in patients receiving lymph node dissection.Lymph node metastasis is associated with primary tumor location and diameter,levels of CEA and TBil.Lymph node metastasis rate in left liver is higher than that in right liver,and is getting higher with increased primary tumor diameter.

Objective To quantitatively assess the plan quality of conventional fractionated volumetric modulated arc therapy ( VMAT ) plans for liver cancer treatments using flattening filter-free (FFF) and flattening filter (FF) modes based on plan quality metric (PQM). Methods A total of ten patients with liver tumor were selected. The patients were planned in FF and FFF mode of 6 MV X-ray respectively. The dose distribution of the planning target volume ( PTV) and the organ at risk ( OAR) were evaluated, and the monitor units ( MUs) and the beam on time ( BoT) were compared. According to the clinical requirements, a PQM with 16 submetrics was defined to evaluate the plan quality of the two modes. Results The maximal dose of FFF plan was less than that of FF plan (t =3.828, P <0.05). The normalized volume of 5 Gy ( V5 ) and mean dose ( Dmean ) of the normal liver of FFF plan were lower than those of the FF plan (t=2.716, 3.007, P<0.05). The average MU of FFF plan [(574 ± 130) MU] was higher than that of FF plan [(518 ± 81) MU](t= -2. 782,P<0. 05), while the average BoT of FFF plan [(108 ±36)s] was significantly lower than that of FF plan [(160 ±29) s](t=6.767,P<0.05). The score of FFF plan was higher than that of FF plan (t= -2.746, P<0.05). Conclusions FFF mode can better protect the OAR at low dose levels. The MU of FFF mode plan were higher, but the beam on time was significantly lower than FF mode plan. With reference to the PQM evaluation criteria, the overall plan quality of the FFF mode was slightly higher.

Objective: To explore the characteristics underlying Th1/Th2/Th17 expression level after entecavir (ETV) discontinuation of chronic hepatitis B (CHB) patients who were HBeAg-positive and define the role of Th1/Th2/Th17 in maintaining virological response after ETV discontinuation. Methods: We selected 112 HBeAg positive CHB patients who met the withdrawal criteria according to the guideline of prevention and treatment of chronic hepatitis B (2010 version), and we also separated them into virology sustained response (SVR) group and virological relapse (VR) group according to the recurrence in 52 weeks. We detected serum level of Th1/Th2/h17 related cytokines during 0, 12, 24 and 52 weeks follow-up to further analyze their dynamic changes and expression differences. Results: The results of the study reveals that serum levels of IFN-γ in the group of SVR were at a higher level compared with VR group during follow-up (all P<0.05). While, the serum level of IL-10 decreased in SVR group and was lower than the paired IL-10 level in VR group with significance during follow-up. In VR group, the serum level of IFN-γ decreased during the first 24 weeks after ETV withdrawal, and after then, the level rose. The serum levels of IFN-γ (Th1) in SVR patients were significantly higher than those in VR patients in the different follow-up time points after ETV discontinuation (all P<0.05). And the serum levels of IL-10 (Th2) in SVR patients were significantly lower than that in VR patients (all P<0.05). The comparison of serum levels of IL-17A (Th17) between the two groups had no significant difference (all P>0.005). Conclusions The serum level of IFN-γ in SVR group maintained a high level is conducive to maintaining virological response after ETV withdrawal and high level of IL-10 may be related to virologic relapse.

Objective To study the correlation between interleukin(IL)-21 and the recurrence of chronic hepatitis B(CHB)in hepatitis B e antigen(HBeAg)-positive patients after discontinuation of entecavir(ETV).Methods A total of 112 HBeAg-positive CHB patients treated with ETV were enrolled.Serum levels of IL-21 at week 0,12,24 and 52 after ETV discontinuation were detected.The Cox regression model was used to analyze the correlation between IL-21 and the recurrence after ETV discontinuation.The receiver operating characteristic(ROC)curve was applied to determine the predictive value of IL-21 for CHB recurrence after ETV discontinuation.The expression differences of IL-21 were compared between sustained viral response(SVR)group and viral relapse(VR)group.The t test and Chi-square test were used for statistical analysis.Results The serum levels of IL-21 in SVR group at week 0,12,24 and 52 after ETV withdrawal were(60.0 ± 10.8),(60.2 ± 14.7),(60.6 ± 19.5)and (61.2 ± 15.4)ng/L,respectively,which were all significantly higher than those in VR group(47.5 ± 10.7),(47.3 ± 12.9),(46.9 ± 12.2)and(46.4 ± 12.8)ng/L,respectively(t=6.153,4.926,4.382 and 5.515,respectively,all P< 0.01).The area under curve(AUC)was 0.811(95% CI:0.728 ~0.893,P<0.01)and the best cut-off value of serum IL-21 level was 49.8 ng/L.The recurrence rates of patients with serum IL-21 level ≥49.8 ng/L and <49.8 ng/L at time of ETV withdrawal was 25.4%(16/63)and 77.6%(38/49),respectively.The difference was statistically significant(χ2=30.027,P<0.01).The serum IL-21 level at the time of drug withdrawal(P= 0.005),serum hepatitis B surface antigen(HBsAg)level at the time of HBeAg seroconversion(P= 0.008)and age(P= 0.016)were factors associated with CHB recurrence after ETV withdrawal by multivariate Cox model analysis.The serum levels of ALT,HBV DNA,HBeAg and HBsAg in SVR group were significantly lower than those of VR group at week 12,24 and 52 after ETV withdrawal(t= -5.968,-7.691,-8.093; -3.047,-9.477,-28.900;-2.872,-10.424,-18.330;-4.633,-4.030 and -5.032,respectively;all P<0.01).Serum level of IL-21 was negatively correlated with HBsAg in SVR group after ETV withdrawal (r= -0.241,P<0.01),while positively correlated with HBsAg in VR group(r=0.286,P<0.01). Conclusions The serum IL-21 level at the time of drug withdrawal is associated with the recurrence after ETV discontinuation.IL-2l may play an important role as an immunomodulatory factor in maintaining virological responses in HBeAg-positive CHB patients after ETV withdrawal.

Charged particle therapy offers a better effect and obvious dosimetric and biological advantages over conventional radiotherapy in tumor control.Charged particles form Bragg peak in the dose distribution in tissue, enable most of energy to be deposited in the target region, and thus enhance tumor control and reduce the damage to normal tissues surrounding the tumor.With the increasing demand for charged particle therapy and the advances in particle accelerator, particle therapy technology is developing rapidly.The core apparatus of particle therapy facility is particle accelerator, and the accelerator type, particle type, and implementation technique determine the performance and therapeutic effect of the facility.This article provides a detailed comparative analysis of various particle therapies.Statistical data show that proton therapy is dominant in particle therapy, and high construction difficulty, large facility size, and extremely high cost have limited the development of heavy ion therapy.Nowadays, there are still some technical problems regarding charged particle therapy, and more clinical trials are required.

Objective To evaluate the influence and significance of Pingyangmycin chemotherapy on the c-myc and Ras-P21 protein expression in penile cancer .Methods A total of 100 penile squamous cell carci-noma cases was retrospectively studied and divided into two groups .Data were obtained from 1995 to 2005 .In the chemotherapy group ,50 cases of patients were selected to perform preoperative chemotherapy before surgery .The patients were treated by Pingyangmycin .After 7 times of medication ,partial excision of penis plus improved ingui-nal lymph node dissection was performed .In the control group ,50 cases of patients were selected for partial exci-sion of penis plus improved inguinal lymph node dissection directly without any pre -operative chemotherapy .All pathology specimens were detected of c -myc and Ras-P21 protein expression by immunohistochemical staining assay.Theχ2 test was used for the statistical analysis .Results In chemotherapy group,the positive expression rates of c-myc and Ras-P21 were 30%,27%,respectively.However,in control group,the positive expression rate of c-myc,Ras-P21 were 52%,48%,respectively.By theχ2 test,the expressive differences of c -myc,Ras-P21 positive expression rate between chemotherapy group and control group were all significant (P<0.05). Conclusion The protein expressions of c -myc and Ras-P21 is significantly decreased in the tissue of Pingy-angmycin chemotherapy of penile cancer .