Objective:To understand the current status of pubertal sexual characteristics development of girls aged 6-18 years in Tongzhou District of Beijing and to compare the differences in sexual characteristics development among girls characterized as thin, normal, overweight, and obese.Methods:A cross-sectional survey was conducted among 2 844 girls aged 6-18 years in Tongzhou District of Beijing from September 2022 to July 2023. The developmental stages of breast and pubic hair were assessed on site, and menarche status was inquired. Weight and height were measured. The girls were subsequently characterized into thin, normal, overweight and obese groups. Basic information (including family and personal history) was obtained through questionnaires. Probit probability unit regression was applied to calculate the age of each Tanner stage of sexual characteristics development and the age of menarche. The χ 2 test was applied to compare the counting data between two or multiple groups. Results:A total of 2 844 girls were surveyed and 2 704 girls met the inclusion criteria, resulting in a valid response rate of 95.1%. Among these girls, 1 105 (40.9%) were aged 6-9 years, 1 053 (38.9%) were aged 10-13 years, and 546 (20.2%) were aged 14-18 years. The of height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), and body mass index-for-age Z-score (BAZ) were 0.46(-0.23,1.16), 0.69(-0.16,1.67), and 0.67(-0.27,1.73) respectively. The prevalences of thin, overweight, and obesity were respectively 1.7% (45/2 704), 17.3% (467/2 704), and 19.9% (538/2 704), respectively. There were 45 girls in the thin group, 1 654 girls in the normal weight group, 1 005 girls in the overweight and obesity group. The age of Tanner stage breast 2 (B2), Tanner stage pubic hair 2 (P2), and menarche was 9.0 (95% CI 8.9-9.1), 10.5 (95% CI 10.4-10.6), and 11.4 (95% CI 11.3-1.5) years, respectively. The current status of breast and pubic hair maturity in girls with pubertal development shows that 64.6% (1 211/1 874) of these girls had breast development preceding pubic hair development, 32.4% (607/1 874) had concurrent breast and pubic hair development, and 3.0% (56/1 874) had pubic hairs development preceding breast development. The interval age between B2 and B5 was 4.7 (95% CI 4.6-4.8) years, between P2 and P5 was 4.5 (95% CI 4.4-4.6) years, and between B2 and menarche was 2.4 (95% CI 2.3-2.5) years. The ages of sexual characteristics development in overweight and obese groups were earlier than that in normal and thin groups. The ages of B2 in thin, normal, overweight, and obese groups were 10.0 (95% CI 9.5-10.6), 9.3 (95% CI 9.2-9.4), and 8.6 (95% CI 8.4-8.7) years, respectively. The age of menarche in thin, normal, overweight, and obese groups were 13.1 (95% CI 12.4-13.7), 11.6 (95% CI 11.4-11.7), and 11.1 (95% CI 11.0-11.2) years, respectively. The interval ages between B2 and B5 and between P2 and P5 was 4.5 and 4.1 years, respectively in the overweight and obese groups, and those in normal group and thin group was 4.7 and 4.5 years, 4.6 and 4.7 years, respectively. Conclusions:The ages of sexual characteristics development and menarche tend in Tongzhou District of Beijing to be earlier than that being reported of Beijing's survey 20 years ago. Girls characterized as overweight and obese not only start puberty at an earlier age than girls of normal weight, but also have a shorter developmental process.

Abstract：Objective To optimize the production process of inactivated vaccine of Aeromonas veronii（AV）CA07 strain. Methods The fermentation culture process of AV CA07 strain liquid was determined through the optimization of the culture time（2～16 h），medium（optimized fermentation medium，LB medium and NB medium）and fermentation conditions（in⁃ oculation amount of 1%，5%，10% and 15%；ventilation rate of 2，4，6 and 8 L／min and fermentation time of 6，8，10 and 12 h）. The optimal inactivation process was determined through the comparison of the final concentration of formalde⁃ hyde solution（0. 10%，0. 20%，0. 30% and 0. 40%），inactivation temperature（28 and 37 ℃）and inactivation time（24， 48 and 72 h）. The large⁃scale production process of inactivated vaccine of AV CA07 strain in 500 L fermentor was estab⁃ lished and the prepared vaccines were tested for safety and immunogenicity. Results The optimal inoculation amount of AV CA07 strain was 5%，ventilation rate was 4 L／min and culture time was 10 ~ 12 h. The optimal inactivation condition was adding formaldehyde solution with final concentration of 0. 30% incubating at 37 ℃ for 24 h. The number of viable bacteria in the fermentation broth of AV CA07 strain prepared in 500 L fermentor was more than 8 × 109 CFU／mL. All crucian carps immunized with the inactivated vaccine by abdomen survived. After challenge，the relative immune protection rate was more than 90%. Conclusion AV CA07 strain inactivated vaccine prepared by optimized production process showed good safety and immunogenicity.

OBJECTIVE: To observe the effect of needle knife on chondrocyte autophagy and expressions of autophagy-related protein and mammalian target of rapamycin (mTOR) in rats with knee osteoarthritis (KOA), and to explore the possible mechanism of needle knife for KOA. METHODS: A total of 42 SD rats were randomly divided into a normal group, a model group and a needle knife group, 14 rats in each group. Except for the normal group, the other two groups were injected with the mixture of papain and L-cysteine into the left hind knee joint to establish the KOA model. After modeling, the rats in the needle knife group were treated with needle knife at strip or nodule around the quadriceps femoris and medial and lateral collateral ligament on the affected side, once a week for 3 times (3 weeks). The changes of left knee circumference in each group were observed; the chondrocytes and ultrastructure of left knee joint were observed by HE staining and electron microscope; the mRNA and protein expressions of autophagy-related genes (Atg5, Atg12, Atg4a), Unc-51 like autophagy activated kinase 1 (ULK1), autophagy gene Beclin-1 and mTOR in left knee cartilage were detected by real-time fluorescence quantitative PCR and Western blot. RESULTS: After modeling, the left knee circumferences in the model group and the needle knife group were increased compared with those before modeling and in the normal group (P<0.05); after intervention, the left knee circumference in the needle knife group was smaller than that in the model group and after modeling (P<0.05). Compared with the normal group, the number of chondrocytes was decreased, and a few cells swelled, nuclei shrank, mitochondria swelled and autophagosomes decreased in the model group; compared with the model group, the number of chondrocytes was increased , and most cell structures returned to normal, and autophagosomes was increased. Compared with the normal group, the mRNA and protein expressions of Atg5, Atg12, Atg4a, Beclin-1 and ULK1 in the knee cartilage in the model group were decreased (P<0.05); compared with the model group, the expressions of the above indexes in the needle knife group were increased (P<0.05). Compared with the normal group, the mRNA and protein expressions of mTOR in the knee cartilage in the model group were increased (P<0.05); compared with the model group, the expressions of the above indexes in the needle knife group were decreased (P<0.05). CONCLUSION The needle knife intervention could improve knee cartilage injury in rats with KOA, and its mechanism may be related to reducing the expression of mTOR and up-regulating the expressions of Atg5, Atg12, Atg4a, ULK1 and Beclin-1, so as to promote chondrocyte autophagy and delay the aging and degeneration of chondrocytes.
Animals ; Autophagy ; Autophagy-Related Protein-1 Homolog/genetics* ; Beclin-1/genetics* ; Chondrocytes ; Osteoarthritis, Knee/therapy* ; Rats ; Rats, Sprague-Dawley ; TOR Serine-Threonine Kinases/genetics*

Tumors are new organisms formed by uncontrollable cell proliferation of local tissues driven by various oncogenic factors. The cause of tumors is unknown with life-threating outcome. Tumors can be classified into benign tumors， borderline tumors， and malignant tumors according to their pathological properties. Among them， malignant tumor is commonly known as cancer， with no specific medicines or reliable cure means， so this is a hot spot and difficult point in current medical research. In ancient literatures， there are many records about the efficacy of Chinese herbal medicine in treating tumor， and modern pharmacological researches have shown that more and more active ingredients of traditional Chinese medicine（TCM） have gradually highlighted their inhibitory effect on various types of tumor. Caulis sinomenii has been used for treatment of rheumatic diseases in TCM for a long history. Sinomenine is a major bioactive alkaloid presented in C. sinomenii， which has demonstrated a wide range of pharmacological activities such as anti-inflammation， immunosuppression， analgesia and sedation， and due to its slightly soluble in water， it is commonly used in clinic in the form of hydrochloride， with its commercial name of Zhengqing Fengtongning. Recent studies show that sinomenine alone or combined with chemoradiotherapy can inhibit growth of several tumors significantly or in a synergistic way， so it is termed as an inhibitor of tumors. Anti-tumor effect of sinomenine involve inhibition of tumor cell proliferation， induction of tumor cell apoptosis， blockade of tumor cell cycle， suppression of tumor invasion and metastasis， induction of autophagy of tumor cells， and reversal of multidrug resistance of tumor cells. Upon combination with nanomaterials， it can enhance efficiency and reduce toxicity. Here we summarized and reviewed recent advances on basic anti-tumor research of sinomenine， and then made a classification and description according to its in vivo and in vitro pharmacological action and mechanism of action， so as to elucidate the great potential of sinomenine as a promising anti-tumor drug， and provide reference for further research on its anti-tumor mechanism.

Objective: To observe the effects of laurocapram and borneol as transdermal penetration enhancers applied to herbal cake-partitioned moxibustion on liver lipids, hormone-sensitive lipase (HSL) and hydroxymethylglutaryl CoA (HMG-CoA) reductase in hyperlipidemia rabbits.Methods: Forty New-Zealand rabbits were randomly divided into 5 groups using the random number table method, with 8 rats in each group. Rabbits in the blank group were fed routinely with a normal diet; rabbits in the other groups were fed with high-fat diet for 12 weeks to establish the hyperlipidemia model. Rabbits in the blank and the model groups were not given any intervention. After the model was prepared successfully, rabbits in the non-transdermal penetration enhancer group received herbal cake-partitioned moxibustion without transdermal penetration enhancers; rabbits in the laurocapram group and the borneol group received herbal cake-partitioned moxibustion with laurocapram or borneol respectively. After 4 weeks of treatment, the serum was isolated and enzyme-linked immunosorbent assay (ELISA) was applied for the detection of HSL and HMG-CoA reductase. The liver tissues were isolated, and total cholesterol (TC) and triglycerides (TG) were measured by enzymatic methods. One-step method was applied for high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) detection, and transmission turbidimetry was for apolipoprotein A1 (Apo-A1) and apolipoprotein B (Apo-B) detection. Results: The serum concentrations of the drugs in the laurocapram and the borneol groups were significantly higher than those in the non-transdermal penetration enhancer group (both P<0.05); all drug penetrations in the borneol group were significantly higher than those in the laurocapram group (both P<0.05), except for tanshinone ⅡA. Compared with the non-transdermal penetration enhancer group, the HSL was significantly increased while the HMG-CoA reductase was significantly decreased in the laurocapram and the borneol groups (both P<0.05); between groups, the HSL in the borneol group was significantly higher than that in the laurocapram group (P<0.05). Compared with the blank group, the levels of LDL-C, TG, TC and Apo-B in rabbit liver were significantly increased in the model group (P<0.05); compared with the model group, the levels of LDL-C, TG, TC and Apo-B in the non-transdermal penetration enhancer, the laurocapram, and the borneol groups were significantly decreased (all P<0.05); between groups, the TG and TC in the laurocapram group and the LDL-C, TG, TC and Apo-B in the borneol group were significantly lower than those in the non-transdermal penetration enhancer group (all P<0.05), and the TG, LDL-C and Apo-B in the borneol group were significantly lower than those in the laurocapram group (all P<0.05). Compared with the blank group, the HDL-C and Apo-A1 were significantly decreased in the model group (both P<0.05), while compared with the model group, the HDL-C and Apo-A1 were significantly increased in the non-transdermal penetration enhancer, the laurocapram, and the borneol groups (all P<0.05). Between groups, the Apo-A1 in the laurocapram group, the HDL-C and Apo-A1 in the borneol group were significantly higher than those in the non-transdermal penetration enhancer group (all P<0.05).Conclusion: The application of laurocapram and borneol, as transdermal penetration enhancers, in herbal cake-partitioned moxibustion can promote the penetration of the drugs in the herbal cake, increase the levels of HDL-C and Apo-A1, improve the metabolism of HSL and HMG-CoA reductase, and also simultaneously reduce the levels of TC, TG, LDL-C and Apo-B in the liver. The transdermal penetration enhancement effect of borneol is slightly better than or equivalent to that of laurocapram.

Objective:To observe the controlling effect of addition and subtraction therapy of Xuanbi tang on knee osteoarthritis of rheumatic fever arthralgia type (KOA) at attack stage and to investigate the influence to acute inflammation factors. Method:One hundred and twenty-eight patients were randomly divided into control group and observation group (1∶1) by random number table with SAS software. The patients in both groups got celecoxib capsules, 0.2 g/time, 1 time/day, glucosamine hydrochloride capsule, 1 grain/time, 2 times/day. Patients in control group addiiontally got Simiaowan, 6 g/time, 2 times/day. Patients in observation group got addition and subtraction therapy of Xuanbitang, 1 dose/day, with a treatment course of 2 weeks in both groups. Visual analogue scale of pain (VAS) was used to discuss pain degree of knee joint, and the VAS scores during activity and resting state were recorded every day, and the time to pain relief and time to pain disappearance were also recorded. Before and after treatment, the scores of osteoarthritis index visual scale of Western Ontario and McMaster University (WOMAC), scores of swelling degree and scores of rheumatism heat arthralgia syndrome were graded. The levels of high sensitive C-reactive protein (hs CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and serum matrix metalloproteinase-3 (MMP-3) were detected before and after treatment. In addition, safety was evaluated and discussed. Result:The comprehensive total effective rate in observation group was 95.00% (57/60), higher than 83.05% (49/59) in control group (P<0.05). At the third, seventh, tenth, fourteenth day after treatment, scores of knee joint pain degree in observation group were lower than those in control group (P<0.01). Time to pain relief and time to pain disappearance were shorter than those in control group (P<0.01). Scores of WOMAC, swelling degree and rheumatism heat arthralgia syndrome were all lower than those in control group (P<0.01). Levels of hs-CRP, IL-1β, IL-6, TNF-α and MMP-3 were lower than those in control group (P<0.01). In addition, there was no adverse reaction related to Xuanbitang. Conclusion:Addition and subtraction therapy of Xuanbitang can relieve pain, swelling and other symptoms, improve knee joint function, shorten the course of disease, and control the acute inflammatory reaction, with significant clinical efficacy and safety.