ObjectiveTo explore the effect and mechanism of the classic famous prescription Anmeidan （AMD） developed in the Qing Dynasty in regulating the hepatic neurotransmitters and circadian rhythm in the rat model of insomnia via the orexin-1 receptor （OX1R）/phosphatidylinositol-specific phospholipase Cβ-1 （PLCβ-1）/protein kinase Cα （PKCα）/extracellular signal-regulated kinase 1/2 （ERK1/2） signaling pathway. MethodSixty SPF-grade SD rats were randomized into blank， model， suvorexant （30 mg·kg^-1·d^-1）， and low-， medium-， and high-dose （4.55， 9.09， 18.09 g·kg^-1·d^-1， respectively） AMD groups， with 10 rats in each group. The rats in other groups except the blank group were modeled by intraperitoneal injection of p-chlorophenylalanine （PCPA） and administrated with corresponding drugs by gavage， and the blank group received an equal volume of normal saline. The general condition， body mass， and 24 h autonomic activity of each group were observed. The pathological changes of the liver tissue were observed by hematoxylin-eosin（HE）staining and Masson staining. The expression of gamma-aminobutyric acid （GABA）， 5-hydroxytryptamine （5-HT）， epinephrine （EPI）， norepinephrine （NE）， and acetylcholine （ACh） in the liver tissue was detected by enzyme-linked immunosorbent assay. The glutamate （Glu） expression in the liver tissue was detected by the biochemical method. The mRNA levels of biological clock genes Per1， Per2， Cry1， Cry2， Bmal1， and Bmal2 in the liver were determined by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. The protein and mRNA levels of factors in the OX1R/PLCβ-1/PKCα/ERK1/2 signaling pathway in the liver were determined by Western blot and Real-time PCR， respectively. ResultCompared with the blank group， the modeling decreased the body mass （P<0.05， P<0.01） and caused mania and disturbed resting rhythms （P<0.01）， hepatic muscle fiber fracture， and edema with inflammatory cell infiltration. In addition， the modeling decreased the GABA， 5-HT， EPI， NE， and ACh content， increased Glu content （P<0.01）， down-regulated the mRNA levels of Per1， Per2， Cry1， and Cry2 （P<0.01）， up-regulated the mRNA levels of Bmal1 and Bmal2 （P<0.01）， and promoted the expression of OX1R， PLCβ-1， PKCα， and ERK1/2 at both protein and mRNA levels （P<0.01）. Compared with the model group， suvorexant and AMD increased the body mass （P<0.05， P<0.01）， alleviated the mania， and increased the resting time and frequency （P<0.05， P<0.01）. Moreover， the medications elevated the levels of GABA， 5-HT， EPI， NE， and ACh， lowered the Glu level， up-regulated the mRNA levels of Per1， Per2， Cry1， and Cry2 （P<0.05， P<0.01）， down-regulated the mRNA levels of Bmal1 and Bmal2， and inhibited the expression of OX1R， PLCβ-1， PKCα， and ERK1/2 at both mRNA and protein levels （P<0.05， P<0.01）. ConclusionAMD can regulate hepatic neurotransmitters and improve circadian rhythm in insomniac rats by inhibiting the OX1R/PLCβ-1/PKCα/ERK1/2 signaling pathway， and high-dose AMD demonstrated the strongest effect.

Lung cancer is the malignant tumor with the highest morbidity and mortality in China. Non-small cell lung cancer (NSCLC) is the main pathological subtype of lung cancer. On April 13, 2023, the National Comprehensive Cancer Network (NCCN) released the third edition of the 2023 NCCN Oncology Clinical Practice Guidelines: Non-small Cell Lung Cancer, which reflects the latest advances in international lung cancer research. This article will interpret the main updated contents of the new edition of the guidelines, and compare it with the third edition of the NCCN guidelines in 2022, so as to provide references about the diagnosis and treatment of NSCLC for clinical medical personnel in China.
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Humans ; Carcinoma, Non-Small-Cell Lung ; China ; Lung Neoplasms ; Thorax

Objective:To summarize the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) infected with Delta variant, so as to provide further references for clinical diagnosis and treatment.Methods:A real-world study was conducted to analyze the characteristics of 166 COVID-19 patients infected with Delta variant at Guangzhou Eighth People’s Hospital, Guangzhou Medical University.Results:The study enrolled 5 asymptomatic cases, 123 non-severe cases (mild and moderate type), and 38 severe cases (severe and critical type). Among these patients, 69 (41.6%) were male and 97 (58.4%) were female, with a mean age of 47.0±23.5 years. Thirty-nine cases (23.5%) had received 1 or 2 doses of inactivated vaccine. The incidence of severe COVID-19 cases was 7.7% in 2-doses vaccinated patients, which was lower than that of 11.5% in 1-dose and 26.8% in unvaccinated patients. The proportion of severe cases in 2 dose-vaccinated patients was 7.7%, which was lower than that of 11.5% in 1-dose vaccinated patients and 26.8% in unvaccinated patients, but the difference was not significant ( P>0.05). The most common clinical symptom was fever (134 cases, 83.2%), and 39.1% of cases presented with high-grade fever (≥39 °C); other symptoms were cough, sputum, fatigue, and xerostomia. The proportion of fever in severe cases was significantly higher than that of non-severe cases (97.4% vs. 76.4%, P<0.01). Similarly, the proportion of severe cases with high peak temperature (≥39 ℃) () was also higher than that of non-severe cases (65.8% vs. 30.9%, P<0.01). The median minimal Cycle threshold (Ct) values of viral nucleic acid N gene and ORFlab gene were 20.3 and 21.5, respectively, and the minimum Ct values were 11.9 and 13.5, respectively. Within 48 h of admission, 9.0% of cases presented with decreased white blood cell counts, and 52.4% with decreased lymphocyte counts. The proportions of increased C-reactive protein, serum amyloid A, interleukin 6, and interleukin 10 were 32.5%, 57.4%, 65.3%, and 35.7%, respectively. The proportions of elevated C-reactive protein, serum amyloid A and interleukin-6 in severe cases were significantly higher than those in non-severe cases ( P<0.01). Logistic regression analysis showed that older age and higher peak temperature were associated with a higher likelihood of severe cases ( OR>3, 95% CI: 2-7, P<0.01). In terms of treatment, traditional Chinese medicine (TCM) was used in 97.6% of non-severe cases and 100% in severe cases. Other treatments included respiratory and nutritional support, immunotherapy (such as neutralizing antibodies and plasma of recovered patients). The median times from admission to progression to severe cases, of fever clearance, and of nucleic acid conversion were 5 days, 6 days and 19 days, respectively. No deaths were reported within 28 days. Conclusions:The symptoms of Delta variant infection in Guangzhou are characterized by a high proportion of fever, high peak temperature, long duration of fever, high viral load, a long time to nucleic acid conversion, and a high incidence of severe cases. The severe cases exhibit a higher percentage of elderly patients, a longer duration of fever and have a higher fever rate and a higher hyperthermia rate than non-severe cases. Age and hyperthermia are independent risk factors for progression to severe disease. The combination of TCM and Western medicine can control the progression of the disease effectively.

Objective:To compare the clinical outcomes between modified percutaneous kyphoplasty (PKP) and conventional PKP in the treatment of Kümmell disease.Methods:A retrospective cohort study was conducted of the 57 patients with single level kummell disease who had undergone PKP between January 2015 and December 2017 at Department of Spinal Surgery, Jiangmen Hospital Affiliated to Sun Yat-sen Uni-versity.Of them, 36 received modified PKP and 21 conventional PKP.In the modified PKP group, there were 24 males and 12 females with an age of 73.9 years±9.4 years and a course of disease of 2.2 months±1.5 months; the disease was located at a thorocic vertebra in 20 cases and at a lumbar vertebra in 16.In the conventional PKP group, there were 15 males and 6 females with an age of 72.6 years±11.9 years and a course of disease of 1.8 months±1.1 months; the disease was located at a thorocic vertebra in 10 cases and at a lumbar vertebra in 11.The 2 groups were compared in terms of operation time, bone cement volume, cement leakage, visual analogue scale (VAS), Oswestry disability index (ODI), anterior and middle heights and cobb angle of injured vertebra at postoperative 3 days, 1 and 3 months, and final follow-up.Results:There were no significant differences in the general clinical data between the 2 groups, showing compatibility between groups ( P>0.05).All the operations were accomplished uneventfully with no such serious complications as spinal cord nerve injury, wound infection, pulmonary embolism, bone cement poisoning reaction or death. There was no significant difference between the 2 groups in operation time or bone cement volume ( P>0.05).The rate of cement leakage in the modified PKP group [33.3%(9/27)] was significantly lower than that [52.4%(11/21)] in the conventional PKP group ( P<0.05).There were no significant differences be-tween the 2 groups in VAS, ODI, anterior or middle height of injured vertebra or cobb angle at postoperative 3 days or one month ( P>0.05), but the postoperative values were improved compared to the preoperative ones.At postoperative 3 months and final follow-up, the modified PKP group was significantly better in all the indexes than the conventional PKP group ( P<0.05). Conclusion:Compared with conventional PKP, the modified PKP may lead to better outcomes for Kümmell disease.

Objective:To analyze the clinicopathological characteristics and treatment strategies of hepatoblastoma with macrotrabecular structures.Methods:To retrospectively analyze the data of children with hepatoblastoma treated in the Department of Oncology at Beijing Children's Hospital affiliated to Capital Medical University amd Baoding Children's Hospital from January 1, 2011 to December 31, 2019. The study structure consisted of collecting clinical data and formulating treatment plan, including clinical stage, alpha-fetoprotein (AFP), chemotherapy plan, surgical margin, pathological classification and follow-up data to study the long-term prognosis of these patients.Results:Among 17 patients, 13 males and 4 females, age 5 to 134 months; 5 patients had the macrotrabecular type, 10 patients had the epithelial type with macrotrabecular, 2 patients had the mixed epithelial and mesenchymal with macrotrabecular type. For the PRETEXT staging, 1 patient had stage I, 2 patients had stage II, 14 patients had stage III and IV. A total of 15 patients received preoperative chemotherapy, and 6 achieved partial response. Among 17 patients, 10 had negative resection margins. The AFP of 7 patients was normal after chemotherapy, and 10 patients relapsed after surgery. The 2-year event-free survival was 26.18%.Conclusions:Patients with hepatoblastoma containing giant trabecular components are very rare. Among them, the recurrence rate of patients with giant trabecular and epithelial and giant trabecular components was high. Preoperative neoadjuvant chemotherapy (vincristine + irinotecan), transcatheter arterial chemoembolization and liver transplantation are treatment options for this type of hepatoblastoma.

Objective:To investigate the effect of complete decongestive therapy in the treatment of severe grade Ⅲ lower limb lymphedema.Methods:From January 2018 to December 2018, The patients were admitted to the lymphedema clinic of the cancer prevention and treatment center of Sun Yat-sen University, seven patients with severe gradeⅢ lower limb lymphedema were intervened with complete decongestive therapy, including problem skin care, special techniques of unarmed lymphatic drainage, foam block bandage combined with air wave pressure therapy, filled elastic bandage pressure bandage, functional exercise combined with home bare-handed lymphatic drainage and weight loss management. The intervention had two courses, and 20 times was a course of treatment. Perimeter measurement and weight measurement were used to evaluate the therapeutic effect at the 0, 5, 10, 15, 20, 30, 40 times of treatment.Results:After two courses of treatment, the circumference value of each measurement point on the affected side was lower than that before treatment, and the difference was statistically significant ( F values were 7.449-23.073, P < 0.05). The circumference value of the affected side decreased by 7.10 - 24.53 cm, and the weight after treatment was 9.0 - 20.5 kg less than that before treatment. During the follow-up period, it was found that the lower extremity diameter value at 3 months of follow-up at 5 sites increased and tended to be stable compared with that at 1 year of follow-up. Conclusion:Step 6 comprehensive swelling treatment can obviously improve the symptoms of patients with lower limb lymphedema of this research, and in the subsequent follow-up found that self-therapy at home, no recurrence or aggravate the limb swelling degree, and can reduce or stability treatment effect, enhance confidence in the treatment of patients, so as to improve the quality of life of patients and treatment compliance.

Objective:To analyze the body composition of breast cancer patients and the changes with age; to compare the incidence of obesity in breast cancer patients with different diagnostic criteria; To understand the relationship between body mass index (BMI) and body composition; to investigate the incidence of sarcopenia and its relationship with obesity in breast cancer patients.Methods:The bioelectrical impedance technique was used to analyze the body composition of 1 187 female breast cancer patients before surgery.Results:There was a statistically significant difference between different age groups of breast cancer patients with various body composition indicators ( F values were 3.767-32.627, P < 0.01), and the incidence of obesity and sarcopenia was different in different age groups ( χ2 value was 20.819, P < 0.01). The obesity detection rate of different diagnostic methods was different. The obesity rate diagnosed by body fat percentage (PBF) was the highest. 28.14% (334/1 187) of breast cancer patients were diagnosed as "invisible obesity", which refers to normal or low BMI but excessive PBF. BMI was positively correlated with all body composition indicators ( r values were 0.137-0.954, P < 0.01), and moderately correlated with PBF and skeletal muscle mass ( r values were 0.761, 0.534, P < 0.01). The incidence of sarcopenia in breast cancer patients was 8.26% (98/1 187). 8.78% (64/1 187) of the patients with normal BMI were diagnosed as Sarcopenia. Among patients with excess PBF and excess visceral fat area, 6.70% (47/1 187) and 5.98% (15/1 187) were diagnosed with sarcopenia, respectively. Conclusion:The incidence of PBF obesity in breast cancer patients is high, and some patients have sarcopenia, which is not good for prognosis. Bioelectrical impedance technology can accurately assess the body composition of patients, and can find "invisible obesity" and sarcopenia that cannot be diagnosed by BMI, which is worthy of further promotion and application in clinical practice.

Objective:To preliminarily evaluate the feasibility and safety of laparoscopic Parks procedure for chronic radiation proctopathy (CRP).Methods:A descriptive cohort study was carried out. The clinical and follow-up data of 19 patients who received laparoscopic Parks procedure due to CRP in the Sixth Affiliated Hospital of Sun Yat-sen University from July 2013 to March 2019 were retrospectively analyzed. Inclusion criteria: (1) serious late complications occurred after pelvic radiotherapy, e.g.serious intractable hematochezia (hemoglobin <70 g/L), intractable anal pain (numerical rating scale >7), rectostenosis, perforation, and fistula. (2) imaging examinations including colonoscopy, pelvic MRI and/or chest, abdomen and pelvic CT were performed before surgery to confirm the lesions. Exclusion criteria: (1) preoperative or intraoperative diagnosis of tumor recurrence; (2) only ostomy was performed after laparoscopic exploration; (3) after neoadjuvant radiotherapy for rectal cancer; (4) incomplete medical records. Surgical procedures: (1) Laparoscopic exploration: tumor recurrence was excluded, and the range of radioactive damage in the intestine was determined. Marks were made on the proximal sigmoid colon without grossly obvious edema, thickening or radioactive injuries. (2) Abdominal operation: the right mesentery of sigmoid colon and rectum was opened, inferior mesenteric vein and inferior mesenteric artery were divided and the Toldt gap was expanded inwards and cephalad. The outside of left hemicolon was freed, the gastrocolic ligament was opened, the splenic flexure was fully mobilized, and the rectum was separated from the rear, side and front to the lowest point. Then perineal operation was performed. (3) Perineal operation: the whole layer of rectum wall was cut thoroughly at 1cm below the lesion's lower margin, the space around the rectum was fully separated, the rectum and sigmoid colon was pulled out through the anus and cut off at the site of the grossly normal intestine, the diseased bowel was removed and a coloanal anastomosis was made. (4) A protective stoma was performed. Conditions of operation, complication and symptom relief were summarized. A descriptive statistic method was used to analyze the results.Results:All the 19 patients were female with a median age of 53 (interquartiles, 50, 56) years old, of whom 18 patients had primary cervical cancer. Surgical indications: 9 cases were rectovaginal fistula; 9 cases were intractable anal pain, among whom 7 were complicated with deep rectal ulcer; and 1 case was intractable hematochezia with deep rectal ulcer. Eighteen cases completed laparoscopic Parks procedure, while 1 case was converted to laparotomy. The median operative time was 215 (131, 270) minutes, the median bleeding volume was 50 (50, 100) ml, and the median hospital stay was 12 (11, 20) days. There was no perioperative death. Ten cases had postoperative complications, including 3 cases of serious complications (CD grade IIIb and above) within 30 days after operation, of whom one case developed pelvic infection caused by rectovaginal, rectovesical and rectourethral fistula and acute renal failure (IVa); 2 cases developed orifice prolapse and parastomal hernia (IIIb). Seven cases had anastomosis-related complications, including 4 cases of grade A anastomotic leakage and 3 cases of anastomotic stenosis. Symptoms of CRP in the whole group were significantly relieved or disappeared after one year of the operation. Five cases achieved stoma closure.Conclusions:Laparoscopic Parks procedure for chronic radiation proctopathy is safe and feasible, and can effectively improve symptoms. However, the incidence of anastomotic complications is high, so the surgical indications should be strictly controlled.

Objective:To preliminarily evaluate the feasibility and safety of laparoscopic Parks procedure for chronic radiation proctopathy (CRP).Methods:A descriptive cohort study was carried out. The clinical and follow-up data of 19 patients who received laparoscopic Parks procedure due to CRP in the Sixth Affiliated Hospital of Sun Yat-sen University from July 2013 to March 2019 were retrospectively analyzed. Inclusion criteria: (1) serious late complications occurred after pelvic radiotherapy, e.g.serious intractable hematochezia (hemoglobin <70 g/L), intractable anal pain (numerical rating scale >7), rectostenosis, perforation, and fistula. (2) imaging examinations including colonoscopy, pelvic MRI and/or chest, abdomen and pelvic CT were performed before surgery to confirm the lesions. Exclusion criteria: (1) preoperative or intraoperative diagnosis of tumor recurrence; (2) only ostomy was performed after laparoscopic exploration; (3) after neoadjuvant radiotherapy for rectal cancer; (4) incomplete medical records. Surgical procedures: (1) Laparoscopic exploration: tumor recurrence was excluded, and the range of radioactive damage in the intestine was determined. Marks were made on the proximal sigmoid colon without grossly obvious edema, thickening or radioactive injuries. (2) Abdominal operation: the right mesentery of sigmoid colon and rectum was opened, inferior mesenteric vein and inferior mesenteric artery were divided and the Toldt gap was expanded inwards and cephalad. The outside of left hemicolon was freed, the gastrocolic ligament was opened, the splenic flexure was fully mobilized, and the rectum was separated from the rear, side and front to the lowest point. Then perineal operation was performed. (3) Perineal operation: the whole layer of rectum wall was cut thoroughly at 1cm below the lesion's lower margin, the space around the rectum was fully separated, the rectum and sigmoid colon was pulled out through the anus and cut off at the site of the grossly normal intestine, the diseased bowel was removed and a coloanal anastomosis was made. (4) A protective stoma was performed. Conditions of operation, complication and symptom relief were summarized. A descriptive statistic method was used to analyze the results.Results:All the 19 patients were female with a median age of 53 (interquartiles, 50, 56) years old, of whom 18 patients had primary cervical cancer. Surgical indications: 9 cases were rectovaginal fistula; 9 cases were intractable anal pain, among whom 7 were complicated with deep rectal ulcer; and 1 case was intractable hematochezia with deep rectal ulcer. Eighteen cases completed laparoscopic Parks procedure, while 1 case was converted to laparotomy. The median operative time was 215 (131, 270) minutes, the median bleeding volume was 50 (50, 100) ml, and the median hospital stay was 12 (11, 20) days. There was no perioperative death. Ten cases had postoperative complications, including 3 cases of serious complications (CD grade IIIb and above) within 30 days after operation, of whom one case developed pelvic infection caused by rectovaginal, rectovesical and rectourethral fistula and acute renal failure (IVa); 2 cases developed orifice prolapse and parastomal hernia (IIIb). Seven cases had anastomosis-related complications, including 4 cases of grade A anastomotic leakage and 3 cases of anastomotic stenosis. Symptoms of CRP in the whole group were significantly relieved or disappeared after one year of the operation. Five cases achieved stoma closure.Conclusions:Laparoscopic Parks procedure for chronic radiation proctopathy is safe and feasible, and can effectively improve symptoms. However, the incidence of anastomotic complications is high, so the surgical indications should be strictly controlled.

Objective:To analyze the genetic and clinical characteristics of MYO15A variants associated non-syndromic autosomal recessive deafness3 (DFNB3).Methods:The hearing test and high-throughput sequencing data of 108 families with non-syndromic hearing loss, who visited the Center of Genetics and Prenatal Diagnosis in the First Affiliated Hospital of Zhengzhou University from November 2016 to February 2019, were retrospectively analyzed to investigate the characteristics of MYO15A variation.Results:Compound heterozygous MYO15A variations were detected in nine patients from eight families, accounting for 7.4% of all 108 families. The variants were c.5910+1G>A/c.9417_9418insTA, c.4234T>G/c.8324G>T, c.3926A>T/c.5002delC, c.9690+1G>A/c.10257_10259delCTT, c.8324G>T/c.10419_10423delCAGCT, c.4519C>T/c.6454G>C, c.6177+1G>T/c.10257_10259delCTT and c.5692C>T/c.7396-1G>A. All patients had severe to profound hearing loss. Among the 14 variations, 12 variations were located in the main structural domains, including 5 in motor domain, 3 in FERM domain, 3 in MyTH4 domain and 1 in IQ motif. The c.3926A>T, c.4234T>G, c.4519C>T, c.5002delC, c.6454G>C, c.8324G>T, c.9417_9418insTA and c.10419_10423delCAGCT had not been reported in the Human Gene Mutation Database up to February 2020. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), 6 reported variants and the first reported c.4519C>T, c.5002delC, c.9417_9418insTA and c.10419_10423delCAGCT were identified as pathogenic variants, while c.8324G>T was likely pathogenic variant, and c.3926A>T, c.4234T>G and c.6454G>C were variants of uncertain significance.Conclusions:The variations of MYO15A in patients with DFNB3 are mainly complex heterozygous. The clinical phenotypes are mostly severe to profound hearing loss, and the mutation loci are mainly in the motor, FERM and MyTH4 domains.